Abstract

Provided herein are methods of treating cancer (e.g., CD38-expressing cancer such as multiple myeloma) using a CD38-binding fusion protein comprising an anti-CD38 antibody fused to one or more attenuated interferon alpha-2b protein in combination an additional anti- CD38 antibody (e.g., daratumumab), and optionally additional agents (e.g., immunomodulatory drugs such as lenalidomide or pomalidomide, or proteasome inhibitors such as bortezomib or carfilzomib), for treating the cancer. In some embodiments, the cancer is multiple myeloma.

IPC Classes  ?

• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 38/21 - Interferons
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C07K 19/00 - Hybrid peptides
• A61P 35/00 - Antineoplastic agents

Abstract

Disclosed herein are modified human interleukin-2 (hIL-2) proteins, human antibody molecules, or antigen-binding fragments thereof, that immunospecifically bind to human programmed cell death protein- 1 (hPD-1), and immunoconjugates comprising the same.

IPC Classes  ?

• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C07K 14/55 - IL-2

Abstract

The present invention provides a combination therapy for treating a tumor in a subject. The combination comprises two elements. The first is a polypeptide construct comprising an attenuated Type I interferon (IFN) linked to an antibody which binds to a cell surface-associated antigen expressed on the tumour cell and comprising a functional Fc region. The second is a CD47 antagonist which inhibits the interaction CD47 with the SIRPα receptor.

IPC Classes  ?

• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• A61K 38/21 - Interferons
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention provides a fusion polypeptide comprising a first domain and a second domain, wherein the first domain comprises a polypeptide ligand which binds to a cell surface-associated antigen and the second domain comprises aglycosylated interferon α 2b (IFNα2b) having a sequence of SEQ ID NO: 1 or SEQ ID NO: 2. The aglycosylated IFNα2b further comprises one or more amino acid substitutions or deletions which attenuate the activity of the aglycosylated IFNα2b.

IPC Classes  ?

• C07K 14/56 - IFN-alpha
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants

Abstract

The present invention provides a fusion polypeptide comprising a first domain and a second domain, wherein the first domain comprises a polypeptide ligand which binds to a cell surface-associated antigen and the second domain comprises aglycosylated interferon α 2b (IFNα2b) having a sequence of SEQ ID NO: 1 or SEQ ID NO: 2. The aglycosylated IFNα2b further comprises one or more amino acid substitutions or deletions which attenuate the activity of the aglycosylated IFNα2b.

IPC Classes  ?

• C07K 14/56 - IFN-alpha
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum

Abstract

The present invention provides a combination therapy for treating a tumor in a subject. The combination comprises two elements. The first is a polypeptide construct comprising an attenuated Type 1 interferon (IFN) linked to an antibody which binds to a cell surface-associated antigen expressed on the tumour cell and comprising a functional Fc region. The second is a CD47 antagonist which inhibits the interaction CD47 with the SIRPα receptor.

IPC Classes  ?

• A61K 38/21 - Interferons
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• A61P 35/00 - Antineoplastic agents

Abstract

Methods for cancer treatment include administering to a cancer patient an anti-CD38 antibody-attenuated human IFN alpha-2b construct and lenalidomide or pomalidomide. Tumors that may be treated according to these methods include tumors which comprise CD-38 expressing tumor cells, including B-cell lymphoma, multiple myeloma, non-Hodgkin's lymphoma, chronic myelogenous leukemia, chronic lymphocytic leukemia, and acute lymphocytic leukemia.

IPC Classes  ?

• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
• A61K 38/21 - Interferons
• C07K 14/56 - IFN-alpha
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
• A61K 39/00 - Medicinal preparations containing antigens or antibodies

Abstract

Antibodies that specifically bind to CD38, as well as constructs comprising such antibodies fused to attenuated interferon alpha-2B proteins are provided. Anti-CD38-attenuated interferon alpha-2b fusion constructs may be used to inhibit proliferation in cancerous cells that express both CD38 and the receptor for IFN-alpha2b, as well as to induce apoptosis in such cells. Inhibition of proliferation and induction of apoptosis in cancerous cells may serve as the basis for the treatment of the underlying cancer.

IPC Classes  ?

• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C07K 14/56 - IFN-alpha
• A61K 38/21 - Interferons
• A61K 38/00 - Medicinal preparations containing peptides
• A61K 39/00 - Medicinal preparations containing antigens or antibodies

Abstract

The present invention provides a combination therapy for treating a tumor in a subject. The combination comprises two elements. The first is a polypeptide construct comprising an attenuated Type 1 interferon (IFN) linked to an antibody which binds to a cell surface- associated antigen expressed on the tumour cell and comprising a functional Fc region. The second is a CD47 antagonist which inhibits the interaction CD47 with the SIRPα receptor.

IPC Classes  ?

• A61K 38/21 - Interferons
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
• A61P 39/00 - General protective or antinoxious agents

Abstract

The present invention provides a combination therapy for treating a tumor in a subject. The combination therapy comprises administration of (i) an antibody which binds to a cell surface-associated antigen expressed on the tumor cell, and (ii) a polypeptide construct comprising an attenuated Type I interferon (IFN) linked to an anti-CD47 antibody. The present invention also provides a polypeptide construct comprising an attenuated Type I interferon (IFN) linked to an anti-CD47 antibody.

IPC Classes  ?

• A61K 38/21 - Interferons
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
• A61P 39/00 - General protective or antinoxious agents

Abstract

The present invention provides a polypeptide construct comprising a peptide or polypeptide signaling ligand linked to an antibody or antigen binding portion thereof which binds to a cell surface-associated antigen, wherein the ligand comprises at least one amino acid substitution or deletion which reduces its potency on cells lacking expression of said antigen.

IPC Classes  ?

• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C07K 14/54 - Interleukins [IL]
• C07K 14/565 - IFN-beta
• C07K 14/57 - IFN-gamma
• C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
• A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
• C07K 14/56 - IFN-alpha
• C07K 16/46 - Hybrid immunoglobulins
• A61K 38/00 - Medicinal preparations containing peptides

Abstract

The disclosure provides TNF-like ligand 1a (TL1a)-binding proteins comprising an antigen binding domain of an antibody which binds specifically to TL1a and inhibits interaction of TL1a and Death Receptor 3 (DR3) and which does not inhibit the interaction of TL1a and Decoy Receptor 3 (DcR3). The disclosure also provides uses of the TL1a-binding proteins.

IPC Classes  ?

• C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
• A61K 39/00 - Medicinal preparations containing antigens or antibodies

Abstract

The present invention provides a fusion polypeptide comprising a first domain and a second domain, wherein the first domain comprises a polypeptide ligand which binds to a cell surface-associated antigen and the second domain comprises aglycosylated interferon α 2b (IFNα2b) having a sequence of SEQ ID NO: 1 or SEQ ID NO: 2. The aglycosylated IFNα2b further comprises one or more amino acid substitutions or deletions which attenuate the activity of the aglycosylated IFNα2b.

IPC Classes  ?

• A61K 38/21 - Interferons
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• C07K 14/56 - IFN-alpha
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C12N 15/21 - Alpha-interferons
• A61P 39/00 - General protective or antinoxious agents

Abstract

The present invention provides a fusion polypeptide comprising a first domain and a second domain, wherein the first domain comprises a polypeptide ligand which binds to a cell surface-associated antigen and the second domain comprises aglycosylated interferon α 2b (IFNα2b) having a sequence of SEQ ID NO: 1 or SEQ ID NO: 2. The aglycosylated IFNα2b further comprises one or more amino acid substitutions or deletions which attenuate the activity of the aglycosylated IFNα2b.

IPC Classes  ?

• C07K 14/56 - IFN-alpha
• C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C12P 21/04 - Cyclic or bridged peptides or polypeptides, e.g. bacitracin

Abstract

Antibodies that specifically bind to CD38, as well as constructs comprising such antibodies fused to attenuated interferon alpha-2B proteins are provided. Anti-CD38-attenuated interferon alpha-2b fusion constructs may be used to inhibit proliferation in cancerous cells that express both CD38 and the receptor for IFN-alpha2b, as well as to induce apoptosis in such cells. Inhibition of proliferation and induction of apoptosis in cancerous cells may serve as the basis for the treatment of the underlying cancer.

IPC Classes  ?

• C07K 14/56 - IFN-alpha
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• A61K 38/00 - Medicinal preparations containing peptides
• A61K 38/21 - Interferons
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 39/00 - Medicinal preparations containing antigens or antibodies

Abstract

Methods for cancer treatment include administering to a cancer patient an anti- CD38 antibody-attenuated human IFN alpha-2b construct and lenalidomide or pomalidomide. Tumors that may be treated according to these methods include tumors which comprise CD-38 expressing tumor cells, including B-cell lymphoma, multiple myeloma, non-Hodgkin's lymphoma, chronic myelogenous leukemia, chronic lymphocytic leukemia, and acute lymphocytic leukemia.

IPC Classes  ?

• C07K 16/46 - Hybrid immunoglobulins
• C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
• C07K 14/56 - IFN-alpha
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 38/21 - Interferons
• A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• A61P 35/00 - Antineoplastic agents

Abstract

Methods for cancer treatment include administering to a cancer patient an anti-CD38 antibody-attenuated human IFN alpha-2b construct and lenalidomide or pomalidomide. Tumors that may be treated according to these methods include tumors which comprise CD-38 expressing tumor cells, including B-cell lymphoma, multiple myeloma, non-Hodgkin's lymphoma, chronic myelogenous leukemia, chronic lymphocytic leukemia, and acute lymphocytic leukemia.

IPC Classes  ?

• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 38/21 - Interferons
• A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C07K 14/56 - IFN-alpha
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

Antibodies that specifically bind to CD38, as well as constructs comprising such antibodies fused to attenuated interferon alpha-2B proteins are provided. Anti-CD38-attenuated interferon alpha-2b fusion constructs may be used to inhibit proliferation in cancerous cells that express both CD38 and the receptor for IFN-alpha2b, as well as to induce apoptosis in such cells. Inhibition of proliferation and induction of apoptosis in cancerous cells may serve as the basis for the treatment of the underlying cancer.

IPC Classes  ?

• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof

Abstract

The present invention provides a polypeptide construct comprising a peptide or polypeptide signaling ligand linked to an antibody or antigen binding portion thereof which binds to a cell surface-associated antigen, wherein the ligand comprises at least one amino acid substitution or deletion which reduces its potency on cells lacking expression of said antigen.

IPC Classes  ?

• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C07K 16/46 - Hybrid immunoglobulins
• C07K 14/56 - IFN-alpha
• C07K 14/54 - Interleukins [IL]
• C07K 14/565 - IFN-beta
• C07K 14/57 - IFN-gamma
• C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses

Abstract

The present invention relates to antibodies, immunoglobulin constructs or immunoglobulin IgG4 fusion proteins whose in vivo half-lives are increased by the combination of (i) a modified IgG4 Fc region or FcRn binding domain thereof and (ii) a modified IgG4 hinge region sequence.

IPC Classes  ?

• C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
• C12P 21/08 - Monoclonal antibodies
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 39/40 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum bacterial
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C07K 1/00 - General processes for the preparation of peptides

Abstract

The present invention provides a polypeptide construct comprising a peptide or polypeptide signaling ligand linked to an antibody or antigen binding portion thereof which binds to a cell surface-associated antigen, wherein the ligand comprises at least one amino acid substitution or deletion which reduces its potency on cells lacking expression of said antigen.

IPC Classes  ?

• C07K 19/00 - Hybrid peptides
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention provides isolated antibodies or antigen binding portions thereof which bind to CD1d. These antibodies and antigen binding portions thereof have application in treatment of conditions involving NKT cell effector function.

IPC Classes  ?

• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• A61P 11/06 - Antiasthmatics
• A61P 17/06 - Antipsoriatics
• A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• A61P 43/00 - Drugs for specific purposes, not provided for in groups
• C12N 15/13 - Immunoglobulins
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells

Abstract

The present disclosure provides TNF-like ligand 1a (TL1a)-binding proteins comprising an antigen binding domain of an antibody which binds specifically to TL1a and inhibits interaction of TL1a and Death Receptor 3 (DR3) and which does not inhibit the interaction of TL1a and Decoy Receptor 3 (DcR3). The present disclosure also provides uses of the TL1a-binding proteins.

IPC Classes  ?

• C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]