Abrégé

BRCA1, BRCA2, CHEK2, MSH2, MSH6, TP53, CDKN1A, BAG6, BRSK2, ERN1, FHIT, HIPK2, EGAES12, ZNF622, AEN, SART1, USP28, GADD45B, TGFB1, NDRG1, WEE1, PPP1R15A, MYBBP1A, SIRT1, ABE1, HRAS, ZNF385B, POER2KDDB2DDB2.

Classes IPC  ?

• C12Q 1/6886 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique pour le cancer
• A61K 31/137 - Arylalkylamines, p. ex. amphétamine, épinéphrine, salbutamol, éphédrine
• A61K 31/198 - Alpha-amino-acides, p. ex. alanine ou acide édétique [EDTA]
• A61K 31/255 - Esters, p. ex. nitroglycérine, sélénocyanates d'acides oxygénés du soufre ou de leurs thio-analogues

Abrégé

The present invention relates to biomarkers of use in cancer therapy, wherein the therapy comprises treatment with anti-Trop-2, anti-CEACAM5 or anti-HLA-DR ADCs (antibody-drug conjugates), alone or in combination with and one or more anti-cancer agents, such as a DDR inhibitor, an ABCG2 inhibitor, a microtubule inhibitor, a checkpoint inhibitor, a PI3K inhibitor, an AKT inhibitor, a CDK 4 inhibitor, a CDK 5 inhibior, a tyrosine kinase inhibitor or a platinum-based chemotherapeutic agent. Preferably, the combination therapy has a synergistic effect on inhibiting tumor growth. The biomarkers are of use to predict efficacy and/or toxicity of ADC therapy, determine tumor response to treatment, identify minimal residual disease or relapse, determine prognosis, stratify patients for initial therapy or to optimize treatment for the patient, based on the specific biomarkers detected.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• A61P 35/04 - Agents anticancéreux spécifiques pour le traitement des métastases
• C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs

Abrégé

The present invention concerns compositions and methods of use of anti-PD-1 antibodies comprising CDR sequences corresponding to SEQ ID NO:1 to SEQ ID NO:6. Preferably the antibody is a humanized antibody comprising the variable region amino acid sequences of SEQ ID NO: 9 and SEQ ID NO:10. The antibodies are of use to treat cancer and may be administered alone or with another standard anti-cancer therapy. The methods may comprise administering the anti-PD-1 antibody or antigen-binding fragment thereof in combination with one or more therapeutic agents such as antibody-drug conjugates, interferons (preferably interferon-α), and/or other checkpoint inhibitor antibodies.

Classes IPC  ?

• C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
• C12N 15/63 - Introduction de matériel génétique étranger utilisant des vecteursVecteurs Utilisation d'hôtes pour ceux-ciRégulation de l'expression
• G01N 33/577 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet faisant intervenir des anticorps monoclonaux
• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• A61P 35/00 - Agents anticancéreux

Abrégé

The present invention relates to methods of cancer therapy using subcutaneous administration of antibody-drug conjugates (ADCs). Preferably, the ADC comprises an antibody that binds to Trop-2, CEACAM5, CEACAM6, CD20, CD22, CD30, CD46, CD74, Her-2, folate receptor, or HLA-DR. More preferably, the drug is SN-38. Subcutaneous administration is at least as effective as intravenous administration of the same ADC. Surprisingly, subcutaneous administration can be used without inducing unmanageable adverse local toxicity at the injection site. Subcutaneous administration is advantageous in requiring less frequent administration, substantially reducing the amount of time required for intravenous administration, and reducing the levels of systemic toxicities observed with intravenous administration. When administered at specified dosages and schedules, the ADCs can reduce solid tumors in size, reduce or eliminate metastases and are effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

Classes IPC  ?

• C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
• A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
• A61K 47/00 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif
• A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier

Abrégé

The present invention relates to treatment of Trop-2 postive cancers with the combination of anti-Trop-2 ADC and a Rad51 inhibitor. Preferably the drug conjugated to the antibody is SN-38, and the ADC is sacituzumab govitecan. The ADC may be administered at a dosage of between 4 mg/kg and 16 mg/kg, preferably 4, 6, 8, 9, 10, 12, or 16 mg/kg. When administered at specified dosages and schedules, the combination of ADC and Rad51 inhibitor can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Surprisingly, the combination is effective to treat cancers that are refractory to or relapsed from irinotecan or topotecan.

Classes IPC  ?

• A61K 31/35 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle
• A61K 31/52 - Purines, p. ex. adénine
• A61K 31/337 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à quatre chaînons, p. ex. taxol
• A61K 31/365 - Lactones
• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
• A61K 47/48 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p.ex. supports, additifs inertes l'ingrédient non actif étant chimiquement lié à l'ingrédient actif, p.ex. conjugués polymère-médicament
• C07K 16/18 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains
• C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
• C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs

Abrégé

The present invention relates to treatment of SCLC with therapeutic ADCs comprising a drug attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. Preferably, the drug is SN-38. More preferably, the antibody is an hRS7 antibody and the ADC is sacituzumab govitecan. The ADC may be administered at a dosage of between 4 mg/kg and 16 mg/kg, preferably 4, 6, 8, 9, 10, 12, or 16 mg/kg, mostly preferably 8 to 10 mg/kg. When administered at specified dosages and schedules, the ADC can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Surprisingly, the ADC is effective to treat cancers that are refractory to or relapsed from irinotecan or topotecan. Preferably, the ADC is administered as a combination therapy with one or more other anti-cancer treatments, such as carboplatin or cisplatinum.

Classes IPC  ?

• A61K 47/68 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un anticorps, une immunoglobuline ou son fragment, p. ex. un fragment Fc
• A61K 31/33 - Composés hétérocycliques
• C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs

Abrégé

The present invention relates to therapeutic ADCs comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. The ADC may be administered at a dosage of between 4 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg, most preferably 8 to 10 mg/kg. When administered at specified dosages and schedules, the ADC can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Preferably, the ADC is administered in combination with one or more other therapeutic agents, such as a PARP inhibitor, a microtubule inhibitor, a Bruton kinase inhibitor or a PI3K inhibitor. Most preferably, the ADC is of use for treating a Trop-2 expressing cancer, such as metastatic urothelial cancer.

Classes IPC  ?

• A61K 47/55 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un composé organique l’agent de modification étant aussi un agent pharmacologiquement ou thérapeutiquement actif, c.-à-d. le conjugué entier étant un co-médicament, p. ex. un dimère, un oligomère ou un polymère de composés pharmacologiquement ou thérapeutiquement actifs
• A61K 47/64 - Conjugués médicament-peptide, médicament-protéine ou médicament-acide polyaminé, c.-à-d. l’agent de modification étant un peptide, une protéine ou un acide polyaminé lié par covalence ou complexé à un agent thérapeutiquement actif
• A61P 35/04 - Agents anticancéreux spécifiques pour le traitement des métastases

Abrégé

Acute kidney injury (AKI) is often associated with damage to remote organs, such as lungs or heart. AKI induces kidney tubular necrosis as well as NETosis, programmed neutrophil death leading to neutrophil extracellular traps (NETs). Histones released during NETosis induces further formation of NETs, which is damaging to renal tissues and remote organs. Circulating trap-forming neutrophils directly injured the lung, while other dead tissue releases contributed to injury in other organs. Suppressing renal necroinflammation using inhibitors of NET formation, tubular cell necrosis or extracellular histones prevented kidney as well as remote organ injuries. Dual inhibition of neutrophil trap formation together with tubular cell necrosis had an additive protective effect. Preferably, damage to remote organs induced by AKI may be treated and/or prevented using anti-histone agents such as anti-histone IgG, recombinant activated protein C, or heparin, alone or in combination with other therapeutic agents, such as PAD inhibitors.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• C07C 259/10 - Composés contenant des groupes carboxyle, un atome d'oxygène d'un groupe carboxyle étant remplacé par un atome d'azote, cet atome d'azote étant lié de plus à un atome d'oxygène et ne faisant pas partie de groupes nitro ou nitroso sans remplacement de l'autre atome d'oxygène du groupe carboxyle, p. ex. acides hydroxamiques ayant des atomes de carbone de groupes hydroxamique liés à des atomes de carbone de cycles aromatiques à six chaînons
• C07C 311/21 - Sulfonamides ayant des atomes de soufre de groupes sulfonamide liés à des atomes de carbone de cycles aromatiques à six chaînons ayant l'atome d'azote d'au moins un des groupes sulfonamide lié à un atome de carbone d'un cycle aromatique à six chaînons

Abrégé

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an anti-HLA-DR antibody or antigen-binding antibody fragment. The immunoconjugate may be administered at a dosage of between 3 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg, more preferably 8, 10 or 12 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. The methods and compositions are particularly useful for treating AML, ALL or multiple myeloma.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• A61K 47/51 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification
• A61P 35/02 - Agents anticancéreux spécifiques pour le traitement de la leucémie
• A61P 35/04 - Agents anticancéreux spécifiques pour le traitement des métastases
• C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
• C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire

Abrégé

The present invention relates to therapeutic ADCs comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment, more particularly sacituzumab govitecan. The ADC is administered to a subject with a Trop-2 positive cancer that is resistant to or relapsed from prior treatment with a checkpoint inhibitor. The therapy is effective to treat cancers that are resistant to checkpoint inhibitors.

Classes IPC  ?

• A61B 6/00 - Appareils ou dispositifs pour le diagnostic par radiationsAppareils ou dispositifs pour le diagnostic par radiations combinés avec un équipement de thérapie par radiations
• A61K 31/17 - Amides, p. ex. acides hydroxamiques ayant le groupe N-C(O)-N ou N-C(S)-N, p. ex. urée, thiourée, carmustine
• A61K 31/282 - Composés du platine
• A61K 31/337 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à quatre chaînons, p. ex. taxol

Abrégé

The present invention relates to combination therapy with drugs, such as Bruton's tyrosine kinase inhibitors or PI3K inhibitors, with antibodies or ADCs against HLA-DR. Where ADCs are used, they preferably incorporate SN-38 or pro-2PDOX. The ADC may be administered at a dosage of between 1 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg. The combination therapy can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Preferably, the combination therapy has an additive effect on inhibiting tumor growth. Most preferably, the combination therapy has a synergistic effect on inhibiting tumor growth.

Classes IPC  ?

• A61K 31/4745 - QuinoléinesIsoquinoléines condensées en ortho ou en péri avec des systèmes hétérocycliques condensées avec des systèmes cycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. phénanthrolines
• A61K 31/704 - Composés ayant des radicaux saccharide liés à des composés non-saccharide par des liaisons glycosidiques liés à un composé carbocyclique, p. ex. phloridzine liés à un système carbocyclique condensé, p. ex. sennosides, thiocolchicosides, escine, daunorubicine, digitoxine
• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
• A61K 47/68 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p. ex. les supports ou les additifs inertesAgents de ciblage ou de modification chimiquement liés à l’ingrédient actif l’ingrédient non actif étant chimiquement lié à l’ingrédient actif, p. ex. conjugués polymère-médicament l’ingrédient non actif étant un agent de modification l’agent de modification étant un anticorps, une immunoglobuline ou son fragment, p. ex. un fragment Fc
• C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
• C40B 30/04 - Procédés de criblage des bibliothèques en mesurant l'aptitude spécifique à se lier à une molécule cible, p. ex. liaison anticorps-antigène, liaison récepteur-ligand
• G01N 33/563 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet faisant intervenir des fragments d'anticorps

Abrégé

The present invention relates to therapeutic ADCs comprising a drug attached to an anti-cancer antibody or antigen-binding antibody fragment. Preferably the drug is SN-38. More preferably the antibody or fragment thereof binds to Trop-2 and the therapy is used to treat a Trop-2 positive cancer. Most preferably the antibody is hRS7. The ADC is administered to a subject with a cancer in combination with an ABCG2 inhibitor. The combination therapy is effective to treat cancers that are resistant to drug alone and/or to ADC alone.

Classes IPC  ?

• A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur
• C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs

Abrégé

The present invention concerns compositions and methods of use of anti-HLA-DR antibodies or fragments thereof. In preferred embodiments, the antibodies are subcutaneously administered to a human patient with a hematologic cancer or autoimmune disease. The subcutaneously administered anti-HLA-DR antibody is effective to treat hematologic cancer or autoimmune disease in patients that have relapsed from or are refractory to standard therapies for hematologic cancer or autoimmune disease, such as administration of anti-CD20 antibodies, such as rituximab.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• A61K 51/10 - Anticorps ou immunoglobulinesLeurs fragments
• C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
• C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
• C07K 16/46 - Immunoglobulines hybrides

Abrégé

The present application discloses compositions and methods of use of 68Ga labeled molecules. Preferably, the 68Ga is attached to a peptide targetable construct and is used in a pretargeting technique with a bispecific antibody (bsAb). The bsAb comprises at least one binding site for a disease-associated antigen, such as a tumor-associated antigen, and at least one binding site for a hapten on the targetable construct. Exemplary haptens include In-DTPA and HSG. More preferably, the bsAb is administered about 24-30 hours before the targetable construct, and detection by PET imaging occurs about 1-2 hours after the targetable construct is administered. The methods and compositions are suitable for detection, diagnosis and/or imaging of various diseases, such as cancer or infectious disease.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• A61K 51/00 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo
• A61K 51/08 - Peptides, p. ex. protéines
• C07K 1/13 - Marquage de peptides
• G01N 33/574 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet pour le cancer

Abrégé

The present invention concerns improved methods and compositions for preparing SN-38 conjugates of proteins or peptides, preferably immunoconjugates of antibodies or antigen-binding antibody fragments. More preferably, the SN-38 is attached to the antibody or antibody fragment using a CL2A linker, with 1-12, more preferably 6-8, alternatively 1-5 SN-38 moieties per antibody or antibody fragment. Most preferably, the immunoconjugate is prepared in large scale batches, with various modifications to the reaction scheme disclosed herein to optimize yield and recovery in large scale. Other embodiments concern optimized dosages and/or schedules of administration of immunoconjugate to maximize efficacy for disease treatment and minimize side effects of administration.

Classes IPC  ?

• A61K 31/4745 - QuinoléinesIsoquinoléines condensées en ortho ou en péri avec des systèmes hétérocycliques condensées avec des systèmes cycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. phénanthrolines
• A61K 45/06 - Mélanges d'ingrédients actifs sans caractérisation chimique, p. ex. composés antiphlogistiques et pour le cœur

Abrégé

The present invention relates to combination therapy with drugs, such as microtubule inhibitors, PARP inhibitors, Bruton kinase inhibitors or PI3K inhibitors, with antibodies or immunoconjugates against HLA-DR or Trop-2. Where immunoconjugates are used, they preferably incorporate SN-38 or pro-2PDOX. The immunoconjugate may be administered at a dosage of between 1 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg, more preferably 8 or 10 mg/kg. The combination therapy can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Preferably, the combination therapy has an additive effect on inhibiting tumor growth. Most preferably, the combination therapy has a synergistic effect on inhibiting tumor growth.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• A61P 35/00 - Agents anticancéreux
• C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs

Abrégé

The present invention concerns CAR, CAR-T and CAR-NK constructs, preferably comprising a scFv antibody fragment against a disease-associated antigen or a hapten. More preferably, the antigen is a TAA, such as Trop-2. The constructs may be administered to a subject with a disease, such as cancer, autoimmune disease, or immune dysfunction disease, to induce an immune response against disease-associated cells. Where the constructs bind to a hapten, the subject is first treated with a hapten-conjugated antibody that binds to a disease associated antigen. Therapy may be supplemented by other treatments, such as debulking procedures (e.g., surgery, chemotherapy, radiation therapy) or coadministration of other agents. More preferably, administration of the construct is preceded by predosing with an unconjugated antibody that binds to the same disease-associated antigen. Most preferably, an antibody against CD74 or HLA-DR is administered to reduce systemic immunotoxicity induced by the constructs.

Classes IPC  ?

• A61K 35/12 - Substances provenant de mammifèresCompositions comprenant des tissus ou des cellules non spécifiésCompositions comprenant des cellules souches non embryonnairesCellules génétiquement modifiées
• A61K 35/17 - LymphocytesLymphocytes BLymphocytes TCellules tueuses naturellesLymphocytes activés par un interféron ou une cytokine
• A61K 39/385 - Haptènes ou antigènes, liés à des supports
• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire

Abrégé

The present invention concerns methods and compositions for treatment of HIV infection using a T20 expression vector, such as that shown in SEQ ID NO:1 or SEQ ID NO:3. The T20 expression vector may be used in a variety of therapeutic applications, such as ex vivo transfection of dendritic cells to induce a host immune response to HIV, localized transfection in vivo in a gene therapy approach to provide longer term delivery of T20, or in vitro production of T20 peptide. The T20 may be secreted into the circulation to act as a fusion inhibitor of HIV infection, or may induce an endogenous immune response to HIV or HIV-infected cells. Alternatively, a DDD peptide may be incorporated in a fusion protein comprising T20 or another antigenic protein or peptide to enhance the immune response to the protein or peptide.

Classes IPC  ?

• C07K 14/16 - HIV-1
• A61K 38/16 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés
• A61P 31/18 - Antiviraux pour le traitement des virus ARN du HIV

Abrégé

Described herein are compositions and methods of use of anti-Trop-2 antibodies or antigen-binding fragment thereof to isolate, enrich, detect, diagnose and/or characterize circulating tumor cells (CTCs) from patients with a Trop-2 positive cancer. Preferably, the antibody is an RS7, 162-46.2 or MAB650 antibody. The compositions and methods are of use to detect, diagnose and/or treat metastatic Trop-2+ cancers, such as breast, ovarian, cervical, endometrial, lung, prostate, colon, rectum, stomach, esophageal, bladder, renal, pancreatic, thyroid, epithelial or head-and-neck cancer.

Classes IPC  ?

• C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
• G01N 33/53 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet
• G01N 33/574 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet pour le cancer
• A61K 47/18 - AminesAmidesUréesComposés d’ammonium quaternaireAcides aminésOligopeptides ayant jusqu’à cinq acides aminés

Abrégé

The present invention relates to use of 90Y-conjugated anti-CD22 antibody for treatment of relapsed/refractory acute lymphoblastic leukemia (ALL). Preferably the anti-CD22 antibody is epratuzumab tetraxetan. More preferably, the radiolabeled antibody is administered at a dosage of between 2.5 and 10.0 mCi/m2, most preferably on days 1 and 8 of the cycle. In specific embodiments, the dosage may be 2.5, 5.0, 7.5 or 10.0 mCi/m2. The radiolabeled antibody is capable of inducing a complete response in individuals with relapsed/refractory ALL.

Classes IPC  ?

• A61K 51/00 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo
• A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• A61K 38/00 - Préparations médicinales contenant des peptides

Abrégé

The present invention concerns methods of treating relapsed/resistant non-Hodgkin's lymphoma using combination therapy with an anti-CD20 antibody or fragment and an anti-CD74 antibody or fragment. In preferred embodiments, the antibody combination is administered along with at least one other therapeutic agent. The combination is effective to treat indolent NHL that is resistant to or relapsed from at least one therapy for NHL, including but not limited to rituximab resistant NHL. The antibody combination may be administered to human subjects at specific dosages and dosing schedules, that are effective to treat the disease but do not induce a dose-limiting toxicity.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire

Abrégé

The present application discloses compositions and methods of use of dual-labeled molecules comprising a fluorescent probe and a radionuclide. The labeled molecules are of use for detection, imaging and/or diagnosis of diseased tissues, such as tumors. In preferred embodiments, the dual-labeled molecules are of use in pre-operative and/or intraoperative imaging, for example to detect margins of malignant tissues to facilitate surgical resectioning. In more preferred embodiments, a radioprotective agent such as an oxygen radical scavenger is used to decrease radiolysis of the fluorescent signal. The labeled molecules bind to a disease-associated antigen, such as a tumor-associated antigen. Exemplary molecules include antibodies, antibody fragments, bispecific antibodies, targetable constructs and targeting peptides, such as bombesin analogues.

Classes IPC  ?

• A61K 51/00 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo
• A61B 5/00 - Mesure servant à établir un diagnostic Identification des individus

Abrégé

The present invention relates to methods and compositions for pretargeting delivery of alpha-emitting radionuclides, such as213Bi or225Ac to a target cell or tissue, such as a cancer cell or a tumor. In preferred embodiments, the pretargeting method comprises: a) administering a bispecific antibody comprising at least one binding site for a tumor-associated antigen (TAA) and at least one binding site for a hapten; and b) administering a hapten-conjugated targetable construct that is labeled with an alpha-emitting radionuclide. More preferably, the bispecific antibody is rapidly internalized into the target cell, along with the radionuclide. In most preferred embodiments, the bispecific antibody is made as a dock-and-lock (DNL) complex.

Classes IPC  ?

• C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
• C07K 16/32 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des produits de traduction des oncogènes
• A61K 39/385 - Haptènes ou antigènes, liés à des supports

Abrégé

The present application discloses compositions and methods of synthesis and use of labeled targeting peptides, such as octreotide, octreotate, or other somatostatin analogs or derivatives. The targeting peptide may be labeled with a therapeutic or diagnostic isotope, such as 61Cu, 62Cu, 64Cu, 67Cu, 18F, 19F, 66Ga, 67Ga, 68Ga, 72Ga, 111In, 177Lu, 44Sc, 47Sc, 86Y, 88Y, 90Y, 45Ti or 89Zr, preferably 18F or 19F. More preferably, the targeting peptide is NOTA-octreotate, NOTA-MPAA-octreotate, pyridine-NOTA-octreotate or triazole-NOTA-octreotate. The labeled targeting peptides may be used for detection, diagnosis, imaging and/or treatment of sst2+ tumors, such as neuroendocrine tumors.

Classes IPC  ?

• A61K 51/00 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo
• A61K 38/04 - Peptides ayant jusqu'à 20 amino-acides dans une séquence entièrement déterminéeLeurs dérivés

Abrégé

The present invention concerns improved methods and compositions for neoadjuvant use of antibody-drug conjugates (ADCs) in cancer therapy, preferably ADCs comprising an anthracycline or camptothecin, more preferably SN-38 or pro-2-pyrrolinodoxorubicin (P2PDox). The ADC is administered as a neoadjuvant, prior to treatment with a standard anti-cancer therapy such as surgery, radiation therapy, chemotherapy, or immunotherapy. Neoadjuvant use of the ADC substantially improves the efficacy of standard anti-cancer therapy and may debulk a primary tumor or eliminate micrometasteses. In most preferred embodiments, neoadjuvant ADC in combination with a standard anti-cancer therapy is successful in treating cancers that are resistant to standard treatments, such as triple-negative breast cancer (TNBC).

Classes IPC  ?

• A61K 35/00 - Préparations médicinales contenant des substances ou leurs produits de réaction de constitution non déterminée
• A61K 31/166 - Amides, p. ex. acides hydroxamiques ayant des cycles aromatiques, p. ex. colchicine, aténolol, progabide ayant l'atome de carbone d'un groupe carboxamide lié directement au cycle aromatique, p. ex. procaïnamide, procarbazine, métoclopramide, labétalol
• A61K 31/4745 - QuinoléinesIsoquinoléines condensées en ortho ou en péri avec des systèmes hétérocycliques condensées avec des systèmes cycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. phénanthrolines
• A61P 35/04 - Agents anticancéreux spécifiques pour le traitement des métastases

Abrégé

The present invention concerns compositions and methods for detecting and identifying novel cancer genes. The technique involves in vivo fusion of human cancer cells and animal cells, preferably hamster stromal cells, to form hybrid human cancer-animal cells, followed by identification of genes that are overexpressed in the hybrid cells compared to normal or transformed animal cells. The novel oncogenes or their protein products may be utilized for detection and/or diagnosis of human cancer or for development of new cancer therapies targeted against the novel oncogenes or their expressed proteins.

Classes IPC  ?

• C12N 5/28 - Cellules résultant d'une fusion inter-espèces un des partenaires de la fusion étant une cellule humaine
• C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques

Abrégé

The present invention concerns compositions and methods of use of antibodies or antibody fragments that bind to an epitope located within the second cysteine-rich domain (Cys2, amino acid residues 1575-1725) of MUC5AC. The antibodies bind with high specificity and selectivity to pancreatic cancer and are of use for therapy, detection and/or diagnosis of pancreatic cancer. In preferred embodiments, therapeutic antibody may be conjugated to at least one therapeutic agent, such as 90Y. Both in vivo and in vitro detection of pancreatic cancer may be performed with the subject methods and compositions. Specific dosages of radiolabeled antibody and/or gemcitabine, of use in human pancreatic cancer patients, are disclosed herein.

Classes IPC  ?

• A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• A61K 51/10 - Anticorps ou immunoglobulinesLeurs fragments

Abrégé

Severe glomerulonephritis involves cell necrosis as well as NETosis, programmed neutrophil death leading to expulsion of nuclear chromatin and neutrophil extracellular traps (NETs). Histones released by neutrophils undergoing NETosis killed glomerular endothelial cells, podocytes, and parietal epithelial cells. This was prevented by histone-neutralizing agents anti-histone IgG, activated protein C and heparin. Histone toxicity on glomeruli was TLR2/4-dependent. Anti-GBM glomerulonephritis involved NET formation and vascular necrosis. Pre-emptive anti-histone IgG administration significantly reduced all aspects of glomerulonephritis, including vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment and activation of glomerular leukocytes and glomerular crescent formation. Subjects with established glomerulonephritis treated with anti-histone IgG, recombinant activated protein C, or heparin all abrogated severe glomerulonephritis suggesting that histone-mediated glomerular pathology is a subsequent, not initial event in necrotizing glomerulonephritis. Neutralizing extracellular histones is therapeutic in severe experimental glomerulonephritis.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
• A61K 36/48 - Fabaceae ou Leguminosae (famille du pois ou des légumineuses)CaesalpiniaceaeMimosaceaePapilionaceae
• A61K 39/38 - Antigènes de serpents

Abrégé

Disclosed are humanized RFB4 antibodies or antigen-binding fragments thereof. therapy of B-cell associated diseases, such as B-cell malignancies, autoimmune disease and immune dysfunction disease. Preferably, hRFB4 comprises the light and heavy chain RFB4 CDR sequences with human antibody FR and constant region sequences, along with heavy chain framework region (FR) amino acid residues Q1, F27, V48, A49, F68, R98, T117 and light chain residues L4, S22, K39, G100, V104, and K107. More preferably, the heavy and light chain variable region sequences of hRFB4 comprise SEQ ID NO:7 and SEQ ID NO:8, respectively. In certain embodiments, trogocytosis (antigen shaving) induced by hRFB4 plays a significant role in determining antibody efficacy and disease responsiveness for treatment of B-cell diseases, such as hematopoietic cancers, immune system dysfunction and/or autoimmune disease.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire

Abrégé

The present application discloses compositions and methods of synthesis and use of 18F-, 19F- or 68Ga-labeled molecules of use in PET, SPECT and/or MRI imaging of prostate cancer. Preferably, the 18F, 19F or 68Ga is attached to a chelator moiety on a prostate cancer targeting molecule, more preferably a bombesin analog, more preferably a GRPR antagonist, most preferably JMV5132 or JMV4168. The 18F or 19F may form a complex with a group IIIA metal to promote binding to the chelators. The labeled molecules may be used to detect, diagnose and/or image prostate cancer, including metastatic prostate cancer, in vivo.

Classes IPC  ?

• A61K 38/04 - Peptides ayant jusqu'à 20 amino-acides dans une séquence entièrement déterminéeLeurs dérivés
• A61K 51/08 - Peptides, p. ex. protéines
• A61K 49/06 - Préparations de contraste pour la résonance magnétique nucléaire [RMN]Préparations de contraste pour l'imagerie par résonance magnétique [IRM]

Abrégé

The present invention concerns compositions and methods of use of a humanized Class III anti-CEA antibody, comprising the heavy and light amino acid sequences SEQ ID NO:1 and SEQ ID NO:2. The antibody is effective to treat CEACAM5-expressing tumors, either alone or in combination with one or more therapeutic agents. Drug conjugated Class III anti-CEA antibodies, such as SN-38 or P2PDox immunoconjugates, are particularly efficacious. Surprisingly, the antibody-drug conjugates (ADCs) exhibit high anti-cancer efficacy, while exhibiting low levels of systemic toxicity that are readily treated with standard amelioration techniques. Antibodies and/or immunoconjugates comprising the amino acid sequences SEQ ID NO:1 and SEQ ID NO:2 are surprisingly efficacious for therapy of solid tumors, even when the tumor has proven resistant to standard anti-cancer therapies.

Classes IPC  ?

• G01N 33/53 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet
• C07K 16/00 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux
• C12N 5/071 - Cellules ou tissus de vertébrés, p. ex. cellules humaines ou tissus humains

Abrégé

Described herein are compositions and methods of use of antibody-drug conjugates (ADCs) comprising an anti-Trop-2 antibody or antigen-binding fragment thereof, conjugated to one or more cytotoxic drugs. Preferably, the antibody is an RS7, 162-46.2 or MAB650 antibody. More preferably, the antibody is humanized. Preferably the drug is SN-38, pro-2-pyrrolinodoxorubicin, paclitaxel, calichemicin, DM1, DM3, DM4, MMAE, MMAD or MMAF. The compositions and methods are of use to treat Trop-2 expressing cancers, such as breast, ovarian, cervical, endometrial, lung, prostate, colon, stomach, esophageal, bladder, renal, pancreatic, thyroid, epithelial or head-and-neck cancer. Preferably, the cancer is one that is resistant to one or more standard cancer therapies. More preferably, the anti-Trop-2 antibody binds to Trop-2 expressed on normal cells, but administration of the anti-Trop-2 ADC to human cancer patients at a therapeutically effective dosage produces only limited toxicity.

Classes IPC  ?

• C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs

Abrégé

The present invention concerns improved methods and compositions for preparing SN-38 conjugates of proteins or peptides, preferably immunoconjugates of antibodies or antigen-binding antibody fragments. More preferably, the SN-38 is attached to the antibody or antibody fragment using a CL2A linker, with 1-12, more preferably 6 or less, most preferably 1-5 SN-38 moieties per antibody or antibody fragment. Most preferably, the immunoconjugate is prepared in large scale batches, with various modifications to the reaction scheme to optimize yield and recovery in large scale. Other embodiments concern optimized dosages and/or schedules of administration of immunoconjugate to maximize efficacy for disease treatment and minimize side effects of administration.

Classes IPC  ?

• A61K 31/4745 - QuinoléinesIsoquinoléines condensées en ortho ou en péri avec des systèmes hétérocycliques condensées avec des systèmes cycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. phénanthrolines
• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• A61K 47/48 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p.ex. supports, additifs inertes l'ingrédient non actif étant chimiquement lié à l'ingrédient actif, p.ex. conjugués polymère-médicament

Abrégé

Described herein are compositions and methods of use of anti-pancreatic cancer antibodies or fragments thereof, such as murine, chimeric, humanized or human PAM4 antibodies. The antibodies show novel and useful diagnostic characteristics, such as binding with high specificity to pancreatic and other cancers, but not to normal or benign pancreatic tissues and binding to a high percentage of early stage pancreatic cancers. Preferably, the antibodies bind to an epitope located within the second to fourth cysteine-rich domains of MUC5ac (amino acid residues 1575-2052) and are of use for the detection and diagnosis of early stage pancreatic cancer. In more preferred embodiments, the anti-pancreatic cancer antibodies can be used for immunoassay of serum samples, wherein the immunoassay detects a marker for early stage pancreatic cancer in serum. Most preferably, the serum is extracted with an organic phase, such as butanol, before immunoassay.

Classes IPC  ?

• G01N 33/574 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet pour le cancer

Abrégé

The present invention concerns chimeric or humanized antibodies or antigen-binding fragments thereof that comprise specific CDR sequences, disclosed herein. Preferably, the antibodies or fragments comprise specific heavy and light chain variable region sequences disclosed herein. More preferably, the antibodies or fragments also comprise specific constant region sequences, such as those associated with the nG1m1,2 or Km3 allotypes. The antibodies or fragments may bind to a human histone protein, such as H2B, H3 or H4. The antibodies or fragments are of use to treat a variety of diseases that may be associated with histones, such as autoimmune disease (e.g., SLE), atherosclerosis, arthritis, rheumatoid arthritis, edema, sepsis, septic shock, hyperinflammatory disorder, infectious disease, inflammatory disease, immune dysregulatory disorder, GVHD, transplant rejection, atherosclerosis, asthma, a coagulopathy, myocardial ischemia, thrombosis, nephritis, inflammatory liver injury, acute pancreatitis, ischemia-reperfusion injury, stroke, cardiovascular disease, and burn.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire

Abrégé

Disclosed are methods, compositions and uses of conjugates of prodrug forms of 2- pyrrolinodoxorubicin (P2PDox) with antibodies or antigen-binding fragments thereof (ADCs), with targetable construct peptides or with other targeting molecules that are capable of delivering the P2PDox to a targeted cell, tissue or pathogen. Once delivered to the target cell, the ADC or peptide conjugate is internalized, a highly toxic 2-pyrrolinodoxorubicin (2- PDox) is released intracellularly. The P2PDox-peptide or ADC conjugates are of use to treat a wide variety of diseases, such as cancer, autoimmune disease or infectious disease.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire

Abrégé

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to EGP-1 (TROP-2), CEACAM5, CEACAM6, CD74, CD19, CD20, CD22, CSAp, HLA-DR, AFP or MUCSac and the immunoconjugate may be administered at a dosage of between 4 mg/kg and 24 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

Classes IPC  ?

• A61K 51/00 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo
• A61M 36/14 - Pansements radioactifs
• A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps

Abrégé

Disclosed are methods and compositions of anti-B cell antibodies, preferably anti-CD22 antibodies, for diagnosis, prognosis and therapy of B-cell associated diseases, such as B-cell malignancies, autoimmune disease and immune dysfunction disease. In certain embodiments, trogocytosis induced by anti-B cell antibodies may determine antibody efficacy, disease responsiveness and prognosis of therapeutic intervention. In other embodiments, optimal dosages of therapeutic antibody may be selected by monitoring the degree of trogocytosis induced by anti-B cell antibodies. Other characteristics of anti-B-cell antibodies that may be monitored include inducing phosphorylation of CD22, CD79a and CD79b; inducing translocation of CD22, CD79a and CD79b to lipid rafts; inducing caspase-dependent apoptosis; increasing pLyn, pERKs and pJNKs; decreasing constitutively-active p38; or inducing mitochondrial membrane depolarization, generation of reactive oxygen species, upregulation of pro-apoptotic Bax and downregulation of anti-apoptotic Bcl-xl, Mcl-1 and Bcl-2.

Classes IPC  ?

• A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
• G01N 33/574 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet pour le cancer
• C12P 21/08 - Anticorps monoclonaux
• C07K 16/00 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux

Abrégé

The present application discloses compositions and methods of use of dye conjugated peptides for fluorescent detection, diagnosis and/or imaging. In preferred embodiments, the compositions comprise a DNL complex comprising an anti-hapten antibody or antigen-binding fragment thereof conjugated to an AD moiety and a DDD moiety conjugated to an antibody or antigen-binding fragment thereof that binds to the target antigen, wherein two copies of the DDD moiety form a dimer that binds to the AD moiety to form the DNL complex. More preferably, the compositions comprise a targetable construct comprising at least one hapten and a fluorescent probe. Binding of the DNL complex to the target antigen and of the hapten on the targetable construct to the DNL complex results in fluorescent labeling of the target antigen. Most preferably, fluorescent imaging is of use in intraoperative, intraperitoneal, laparoscopic, endoscopic or intravascular procedures for detection of diseased tissues.

Classes IPC  ?

• G01N 33/533 - Production de composés immunochimiques marqués avec un marqueur fluorescent
• G01N 21/76 - ChimioluminescenceBioluminescence

Abrégé

Disclosed herein are methods and compositions comprising anti-HLA-DR antibodies for treatment of allogeneic and xenogeneic immune responses occurring in organ transplant rejection and other immune dysfunction diseases. In preferred embodiments, the anti-HLA-DR antibodies are effective to deplete antigen-presenting cells, such as dendritic cells. Most preferably, administration of the therapeutic compositions depletes all subsets of APCs, including mDCs, pDCs, B cells and monocytes, without significant depletion of T cells. In alternative embodiments, administration of the therapeutic compositions suppresses proliferation of allo-reactive T cells, while preserving cytomegalovirus (CMV)-specific, CD8+ memory T cells. The compositions and methods provide a novel therapeutic agent for suppressing or preventing allogeneic or xenogeneic immune responses, without altering preexisting anti-viral immunity.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire

Abrégé

Disclosed herein are methods and compositions comprising fingolimod and anti-CD74 antibodies or fragments thereof. In preferred embodiments, the fingolimod increases the expression of CD74 in target cells and increases the sensitivity of the cells to the cytotoxic effects of the anti-CD74 antibodies. The compositions and methods are of use to treat diseases involving CD74+ cells, such as cancer cells, autoimmune disease cells or immune dysfunction disease cells.

Classes IPC  ?

• A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
• A61P 37/00 - Médicaments pour le traitement des troubles immunologiques ou allergiques
• A61P 35/00 - Agents anticancéreux

Abrégé

Disclosed are methods, compositions and uses of high concentration antibody or immunoglobulin formulations for subcutaneous, intramuscular, transdermal or other local (regional) administration, in a volume of than 3, less than 2 or less than 1 ml. Preferably, the formulation contains a high concentration formulation (HCF) buffer comprising phosphate, citrate, polysorbate 80 and mannitol at a pH of about 5.2. The formulation more preferably comprises at least 100, 150, 200, 250 mg/ml or 300 mg/ml of antibody. The methods for preparing the high concentration formulation include ultrafiltration and diafiltration to concentrate the antibody and exchange the medium for HCF buffer. Other embodiments concern use of non-G1m1 (nG1m1) allotype antibodies, such as G1m3 and/or a nG1m1,2 antibodies. The nG1m1 antibodies show decreased immunogenicity compared to G1m1 antibodies.

Classes IPC  ?

• A61K 51/10 - Anticorps ou immunoglobulinesLeurs fragments

Abrégé

Described herein are compositions and methods of use of anti-pancreatic cancer antibodies or fragments thereof, such as murine, chimeric, humanized or human PAM4 antibodies. The antibodies show novel and useful diagnostic characteristics, such as binding with high specificity to pancreatic and other cancers, but not to normal or benign pancreatic tissues and binding to a high percentage of early stage pancreatic cancers. Preferably, the antibodies bind to pancreatic cancer mucins such as MUC1 or MUC5ac and are of use for the detection and diagnosis of early stage pancreatic cancer. In more preferred embodiments, the anti-pancreatic cancer antibodies can be used for immunoassay of serum samples, wherein the immunoassay detects a marker for early stage pancreatic cancer in serum. Most preferably, the serum is extracted with an organic phase, such as butanol, before immunoassay. Alternatively, immunoassay with PAM4 and anti-CA19.9 antibodies may be utilized to improve sensitivity for pancreatic cancer.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• G01N 33/574 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet pour le cancer

Abrégé

The present application discloses compositions and methods of synthesis and use of 18F or 19F-labeled molecules of use in PET, SPECT and/or MR imaging. Preferably, the 18F or 19F is conjugated to a targeting molecule by formation of a complex with a group IIIA metal and binding of the complex to a bifunctional chelating agent, which may be directly or indirectly attached to the targeting molecule. In other embodiments, the 18F or 19F labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. The disclosed methods and compositions allow the simple and reproducible labeling of molecules at very high efficiency and specific activity in 30 minutes or less. In preferred embodiments, the labeled molecule may be used for imaging in a subject without purification after labeling.

Classes IPC  ?

• A61K 31/33 - Composés hétérocycliques
• C07D 225/00 - Composés hétérocycliques contenant des cycles de plus de sept chaînons ne comportant qu'un atome d'azote comme unique hétéro-atome du cycle
• C07D 255/02 - Composés hétérocycliques contenant des cycles comportant trois atomes d'azote comme uniques hétéro-atomes du cycle, non prévus par les groupes non condensés avec d'autres cycles

Abrégé

The present application discloses compositions and methods of synthesis and use involving click chemistry reactions for in vivo or in vitro formation of therapeutic and/or diagnostic complexes. Preferably, the diagnostic complex is of use for 18F imaging, while the therapeutic complex is of use for targeted delivery of chemotherapeutic drugs or toxins. More preferably, a chelating moiety or targetable construct may be conjugated to a targeting molecule, such as an antibody or antibody fragment, using a click chemistry reaction involving cyclooctyne, nitrone or azide reactive moieties. In most preferred embodiments, the click chemistry reaction occurs in vivo. In vivo click chemistry is not limited to 18F labeling but can be used for delivering a variety of therapeutic and/or diagnostic agents.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire

Abrégé

Disclosed herein are methods and compositions comprising anti-CD74 and/or anti-HLA-DR antibodies for treatment of GVHD and other immune dysfunction diseases. In preferred embodiments, the anti-CD74 and/or anti-HLA-DR antibodies are effective to deplete antigen-presenting cells, such as dendritic cells. Most preferably, administration of the therapeutic compositions depletes all subsets of APCs, including mDCs, pDCs, B cells and monocytes, without significant depletion of T cells. In alternative embodiments, administration of the therapeutic compositions suppresses proliferation of allo-reactive T cells, while preserving cytomegalovirus (CMV)-specific, CD8+ memory T cells. The compositions and methods provide a novel conditioning regimen for preventing aGVHD and/or treating chronic GVHD, without altering preexisting anti-viral immunity.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire

Abrégé

The present invention provides compositions and methods of use of anti-IGF-1R antibodies or fragments. Preferably the antibodies bind to IGF-1R but not IR; are not agonists for IGF-1R; do not block binding of IGF-1 or IGF-2 to isolated IGF-1R; effectively neutralize activation of IGF-1R by IGF-1 in intact cells; block binding of R1 antibody to IGF-1R. The antibodies may be murine, chimeric, humanized or human R1 antibodies comprising heavy chain CDR sequences DYYMY (SEQ ID NO:1), YITNYGGSTYYPDTVKG (SEQ ID NO:2) and QSNYDYDGWFAY (seq id no:3) and light chain CDR sequences KASQEVGTAVA (seq id no:4), WASTRHT (SEQ ID NO:5) and QQYSNYPLT (SEQ ID NO:6). Preferably the antibodies bind an epitope of IGF-1R comprising the first half of the cysteine-rich domain of IGF-1R (residues 151-222). The anti-IGF-1R antibodies may be used for diagnosis or therapy of various diseases such as cancer.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• A61K 51/00 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo
• C07K 16/30 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire provenant de cellules de tumeurs
• C07K 16/46 - Immunoglobulines hybrides

Abrégé

Described herein are compositions and methods of use of anti-pancreatic cancer antibodies or fragments thereof, such as murine, chimeric, humanized or human PAM4 antibodies. The subject antibodies show a number of novel and useful diagnostic characteristics, such as binding with high specificity to pancreatic and other cancers, but not to normal pancreatic tissues and binding to a high percentage of early stage pancreatic cancers. In preferred embodiments, the antibodies bind to pancreatic cancer mucins. The antibodies and fragments are of use for the detection and diagnosis of early stage pancreatic cancer. In preferred embodiments, the anti-pancreatic cancer antibodies can be used for immunoassay of serum samples, wherein the immunoassay can detect a marker for early stage pancreatic cancer in serum. More preferably, the serum is extracted with an organic phase, such as butanol, before immunoassay.

Classes IPC  ?

• G01N 33/53 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet
• A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps

Abrégé

Disclosed herein are methods and compositions comprising interferon-γ (IFN-γ) and anti-CD74 or anti-HLA-DR antibodies. In preferred embodiments, the IFN-γ increases the expression of CD74 and/or HLA-DR in target cells and increases the sensitivity of the cells to the cytotoxic effects of the anti-CD74 or anti-HLA-DR antibodies. The compositions and methods are of use to treat diseases involving CD74+ and/or HLA-DR+ cells, such as cancer cells, autoimmune disease cells or immune dysfunction disease cells.

Classes IPC  ?

• A61K 38/21 - Interférons
• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire

Abrégé

The present invention relates to methods and compositions for pretargeting delivery of therapeutic agents. In preferred embodiments, the pretargeting method comprises: a) administering a bispecific antibody with a first binding site for a disease-associated antigen and a hapten on a targetable construct; b) administering a targetable construct comprising at least one therapeutic agent. In preferred embodiments, the bispecific antibody is made by the dock-and-lock (DNL) technique. In a more preferred embodiment, the targetable construct comprises one or more SN-38 moieties.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire

Abrégé

[0371] The present application discloses compositions and methods of synthesis and use of 68Ga, 18F or 19F labeled molecules of use in PET or MRI imaging. Preferably, the 18F or 19F is conjugated to a targeting molecule by formation of a complex with a group IIIA metal and binding of the complex to a chelating moiety, which may be directly or indirectly attached to the targeting molecule. In other embodiments, the 68Ga, ' F or 19F labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. In more preferred embodiments, a chelating moiety or targetable construct may be conjugated to a targeting molecule, such as an antibody or antibody fragment.

Classes IPC  ?

• C07K 1/13 - Marquage de peptides
• A61K 51/00 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo

Abrégé

Described herein are compositions and methods of use of radionuclide-antibody conjugates (for RAIT) and drug-antibody conjugates (ADC). The combination of RAIT and ADC was more efficacious than either RAIT alone, ADC alone, or the sum of effects of RAIT and ADC. The unexpected synergy resulted in decreased tumor growth rate and increased survival, with a high incidence of tumor-free survival in Capan-1 human pancreatic cancer xenografts in nude mice.

Classes IPC  ?

• A61K 51/00 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo
• A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps

Abrégé

The present invention provides compositions and methods of use of humanized, chimeric or human Class I anti-CEA antibodies or fragments thereof, preferably comprising the light chain variable region CDR sequences SASSRVSYIH (SEQ ID NO:1); GTSTLAS (SEQ ID NO:2); and QQWSYNPPT (SEQ ID NO:3); and the heavy chain variable region CDR sequences DYYMS (SEQ ID NO:4); FIANKANGHTTDYSPSVKG (SEQ ID NO:5); and DMGIRWNFDV (SEQ ID NO:6). The Class I anti-CEA antibodies or fragments are useful for treating diseases, such as cancer, wherein the diseased cells express CEACAM5 and/or CEACAM6 antigens. The Class I anti-CEA antibodies or fragments are also of use for interfering with specific processes, such as metastasis, invasiveness and/or adhesion of cancer cells, or for enhancing sensitivity of cancer cells to cytotoxic agents and have favorable effects on the survival of subjects with cancer.

Classes IPC  ?

• C12P 21/08 - Anticorps monoclonaux

Abrégé

The present invention concerns methods and compositions for forming immunotoxin complexes having a high efficacy and low systemic toxicity. In preferred embodiments, the toxin moiety is a ranpirnase (Rap), such as Rap(Q). In more preferred embodiments, the immunotoxin is made using dock-and-lock (DNL) technology. The immunotoxin exhibits improved pharmacokinetics, with a longer serum half-life and significantly greater efficacy compared to toxin alone, antibody alone, unconjugated toxin plus antibody or even other types of toxin-antibody constructs. In a most preferred embodiment the construct comprises an anti-Trop-2 antibody conjugated to Rap, although other combinations of antibodies, antibody fragments and toxins may be used to form the subject immunotoxins. The immunotoxins are of use to treat a variety of diseases, such as cancer, autoimmune disease or immune dysfunction.

Classes IPC  ?

• A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps

Abrégé

Methods and compositions for forming anti-cancer vaccine complexes are disclosed The vaccine complex comprises an antibody moiety that binds to dendritic cells, such as an antι-CD74 antibody or antigen-binding fragment thereof, attached to an AD (anchoring domain) moiety and a xenoantigen, such as CD20, attached to a DDD (dimerization and docking domain) moiety, wherein two copies of the DDD moiety form a dimer that binds to the AD moiety, resulting in the formation of the vaccine complex The vaccine complex is capable of inducing an immune response against xenoantigen expressing cancer cells, such as CD13S sub neg CD20+ MM stem cells, and inducing apoptosis of and inhibiting the growth of or eliminating the cancer cells

Classes IPC  ?

• A61K 51/00 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo
• A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
• C12P 21/08 - Anticorps monoclonaux

Abrégé

The present invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a therapeutic moiety, and further relates to processes for making and using the conjugates.

Classes IPC  ?

• A61K 39/44 - Anticorps liés à des supports
• C12P 21/08 - Anticorps monoclonaux

Abrégé

The present invention provides humanized, chimeric and human anti-CD19 antibodies, anti-CD19 antibody fusion proteins, and fragments thereof that bind to a human B cell marker. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various B-cell disorders, including B-cell malignancies and autoimmune diseases. In more particular embodiments, the humanized anti-CD19 antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels. In a particularly preferred embodiment, the substitutions comprise a Ser91Phe substitution in the hA19 VH sequence.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire

Abrégé

Described herein are compositions and methods of use of anti-pancreatic cancer antibodies or fragments thereof, such as murine, chimeric, humanized or human PAM4 antibodies. The subject antibodies show a number of novel and useful therapeutic characteristics, such as binding with high specificity to pancreatic and other cancers, but not to normal or benign pancreatic tissues and binding to a high percentage of early stage pancreatic cancers. In preferred embodiments, the antibodies bind to pancreatic cancer mucins. The antibodies and fragments are of use for the detection, diagnosis and/or treatment of cancer, such as pancreatic cancer. The antibodies, such as PAM4 antibodies, bind to a PAM4 antigen that shows unique cell and tissue distributions compared with other known antibodies such as CA19.9, DUPAN2, SPAN1, Nd2, B72.3, and Leaª and Le(y) antibodies that bind to the Lewis antigens.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• G01N 33/53 - Tests immunologiquesTests faisant intervenir la formation de liaisons biospécifiquesMatériaux à cet effet
• C07K 16/00 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux

Abrégé

The present invention provides substituted humanized, chimeric or human anti-CD20 antibodies or antigen binding fragments thereof and bispecific antibodies or fusion proteins comprising the substituted antibodies or antigen binding fragments thereof. The antibodies, fusion proteins or fragments are useful for treatment of B-cell disorders, such as B-cell malignancies and autoimmune diseases, as well as GVHD, organ transplant rejection, and hemolytic anemia and cryoglobulinemia. Amino acid substitutions, particularly substitution of an aspartate residue at Kabat position 101 of CDR3 VH (CDRH3), result in improved therapeutic properties, such as decreased dissociation rates, improved CDC activity, improved apoptosis, improved B-cell depletion and improved therapeutic efficacy at very low dosages. Veltuzumab, a humanized anti-CD20 antibody that incorporates such sequence variations, exhibits improved therapeutic efficacy compared to similar antibodies of different CDRH3 sequence, allowing therapeutic effect at dosages as low as 200 mg or less, more preferably 100 mg or less, more preferably 80 mg or less, more preferably 50 mg or less, most preferably 30 mg or less of naked antibody when administered i.v. or s.c.

Classes IPC  ?

• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• C07K 16/18 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains

Abrégé

The present application discloses compositions and methods of synthesis and use of 18F or 19F labeled molecules of use in PET or MRI imaging. The labeled molecules may be peptides or proteins, although other types of molecules may be labeled. Preferably, the 18F or 19F is conjugated to a targeting molecule by formation of a metal complex and binding of the 18F- or 19F-metal complex to a chelating moiety. Alternatively, the metal may first be conjugated to the chelating group and subsequently the 18F or 19F bound to the metal. In other embodiments, the 18F or 19F labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. The 18F or 19F labeled targetable construct peptides are stable in serum at 37°C for a sufficient time to perform PET or MRI imaging.

Classes IPC  ?

• G01T 1/16 - Mesure de l'intensité de radiation
• G01N 33/00 - Recherche ou analyse des matériaux par des méthodes spécifiques non couvertes par les groupes

Abrégé

The invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a camptothecin as a therapeutic moiety, and further relates to processes for making and using the said conjugates.

Classes IPC  ?

• A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps

Abrégé

The present application discloses compositions and methods of synthesis and use of F-18 labeled molecules of use, for example, in PET imaging techniques. In particular embodiments, the labeled molecules may be peptides or proteins, although other types of molecules including but not limited to aptamers, oligonucleotides and nucleic acids may be labeled and utilized for such imaging studies. In preferred embodiments, the F-18 label may be conjugated to a targeting molecule by formation of a metal complex and binding of the F-18-metal complex to a chelating moiety, such as DOTA, NOTA, DTPA, TETA or NETA. In other embodiments, the metal may first be conjugated to the chelating group and subsequently the F-18 bound to the metal. In other preferred embodiments, the F-18 labeled moiety may comprise a targetable conjugate that may be used in combination with a bispecific or multispecific antibody to target the F-18 to an antigen expressed on a cell or tissue associated with a disease, medical condition, or pathogen. Exemplary results show that F-18 labeled targetable conjugate peptides are stable in human serum at 37°C for several hours, sufficient time to perform PET imaging analysis.

Classes IPC  ?

• A61K 51/00 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo

Abrégé

The present application discloses compositions and methods of synthesis and use of F-18 labeled molecules of use, for example, in PET imaging techniques. In particular embodiments, the labeled molecules may be peptides or proteins, although other types of molecules including but not limited to aptamers, oligonucleotides and nucleic acids may be labeled and utilized for such imaging studies. In preferred embodiments, the F-18 label may be conjugated to a targeting molecule by formation of a metal complex and binding of the F-18-metal complex to a chelating moiety, such as DOTA, NOTA, DTPA, TETA or NETA. In other embodiments, the metal may first be conjugated to the chelating group and subsequently the F-18 bound to the metal. In other preferred embodiments, the F-18 labeled moiety may comprise a targetable conjugate that may be used in combination with a bispecific or multispecific antibody to target the F-18 to an antigen expressed on a cell or tissue associated with a disease, medical condition, or pathogen. Exemplary results show that F-18 labeled targetable conjugate peptides are stable in human serum at 37°C for several hours, sufficient time to perform PET imaging analysis.

Classes IPC  ?

• A61K 49/00 - Préparations pour examen in vivo
• A61M 36/14 - Pansements radioactifs

Abrégé

The present invention concerns methods and compositions for delivery of therapeutic agents to target cells, tissues or organisms. In preferred embodiments, the therapeutic agents are delivered in the form of therapeutic-loaded polymers that may comprise many copies of one or more therapeutic agents. In more preferred embodiments, the polymer may be conjugated to a peptide moiety that contains one or more haptens, such as HSG. The agent-polymer-peptide complex may be delivered to target cells by, for example, a pre-targeting technique utilizing bispecific or multispecific antibodies or fragments, having at least one binding arm that recognizes the hapten and at least a second binding arm that binds specifically to a disease or pathogen associated antigen, such as a tumor associated antigen. Methods for synthesizing and using such therapeutic-loaded polymers and their conjugates are provided.

Classes IPC  ?

• A61K 47/48 - Préparations médicinales caractérisées par les ingrédients non actifs utilisés, p.ex. supports, additifs inertes l'ingrédient non actif étant chimiquement lié à l'ingrédient actif, p.ex. conjugués polymère-médicament

Abrégé

The present invention concerns methods and compositions for treatment of HIV infection in a subject. The compositions may comprise a targeting molecule against an HIV antigen, such as an anti-HIV antibody or antibody fragment. The anti-HIV antibody or fragment may be conjugated to a variety of cytotoxic agents, such as doxorubicin. In a preferred embodiment, the antibody or fragment is P4/D10. Other embodiments may concern methods of imaging, detection or diagnosis of HIV infection in a subject using an anti-HIV antibody or fragment conjugated to a diagnostic agent. In alternative embodiments, a bispecific antibody with at least one binding site for an HIV antigen and at least one binding site for a carrier molecule may be administered, optionally followed by a clearing agent, followed by administration of a carrier molecule conjugated to a therapeutic agent.

Classes IPC  ?

• C12N 7/00 - Virus, p. ex. bactériophagesCompositions les contenantLeur préparation ou purification

Abrégé

The invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a camptothecin as a therapeutic moiety, and further relates to processes for making and using the said conjugates.

Classes IPC  ?

• C07K 16/00 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux
• C12P 21/08 - Anticorps monoclonaux

Abrégé

The present invention concerns methods and compositions for inhibiting angiogenesis and/or tumor growth, survival and/or metastasis. In particular embodiments, the methods and compositions may concern ligands against placenta growth factor (PlGF), such as BP-1, BP-2, BP-3 or BP-4. Some methods may comprise administering one or more PlGF ligands, alone or in combination with one or more other agents, such as chemotherapeutic agents, other anti-angiogenic agents, immunotherapeutic agents or radioimmunotherapeutic agents to a subject. The PlGF ligands are effective to inhibit angiogenesis, tumor cell motility, tumor metastasis, tumor growth and/or tumor survival. In certain embodiments, PlGF ligands may be administered to subjects to ameliorate other angiogenesis related conditions, such as macular degeneration. In some embodiments, PlGF expression levels may be determined by any known method to select those patients most likely to respond to PlGF targeted therapies.

Classes IPC  ?

• A61K 38/17 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
• A61K 48/00 - Préparations médicinales contenant du matériel génétique qui est introduit dans des cellules du corps vivant pour traiter des maladies génétiquesThérapie génique
• A61K 39/395 - AnticorpsImmunoglobulinesImmunsérum, p. ex. sérum antilymphocitaire
• C07H 21/02 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le ribosyle comme radical saccharide

Abrégé

F-18 radiolabeled peptides are prepared by reacting a peptide comprising a hydroxylamine, a thiosemicarbazide, a hydrazine or a free amine group with 4-[18F]Fluorobenzaldehyde. Specific, non-limiting examples of F-18 radiolabeled peptides are described herein. The labeled peptides are useful, for example, in clinical positron emission tomography.

Classes IPC  ?

• A61K 51/00 - Préparations contenant des substances radioactives utilisées pour la thérapie ou pour l'examen in vivo
• A61M 36/14 - Pansements radioactifs

Abrégé

Disclosed are compositions and methods for increasing the longevity of a cell culture and permitting the increased production of proteins, preferably recombinant proteins, such as antibodies, peptides, enzymes, growth factors, interleukins, interferons, hormones, and vaccines. Cells transfected with an apoptosis-inhibiting gene or vector, such as a triple mutant Bcl-2 gene, can survive longer in culture, resulting in extension of the state and yield of protein biosynthesis. Such transfected cells exhibit maximal cell densities that equal or exceed the maximal density achieved by the parent cell lines. Transfected cells can also be pre-adapted for growth in serum-free medium, greatly decreasing the time required to obtain protein production in serum-free medium. In certain methods, the pre-adapted cells can be used for protein production following transformation under serum-free conditions. The method preferably involves eukaryotic cells, more preferably mammalian cells.

Classes IPC  ?

• C12N 5/00 - Cellules non différenciées humaines, animales ou végétales, p. ex. lignées cellulairesTissusLeur culture ou conservationMilieux de culture à cet effet
• C12N 15/00 - Techniques de mutation ou génie génétiqueADN ou ARN concernant le génie génétique, vecteurs, p. ex. plasmides, ou leur isolement, leur préparation ou leur purificationUtilisation d'hôtes pour ceux-ci
• C12N 5/09 - Cellules tumorales