NZ739252B2 - Monoclonal antibodies against bcma - Google Patents
Monoclonal antibodies against bcmaInfo
- Publication number
- NZ739252B2 NZ739252B2 NZ739252A NZ73925216A NZ739252B2 NZ 739252 B2 NZ739252 B2 NZ 739252B2 NZ 739252 A NZ739252 A NZ 739252A NZ 73925216 A NZ73925216 A NZ 73925216A NZ 739252 B2 NZ739252 B2 NZ 739252B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- seq
- antibody
- bcma
- light chain
- specifically binding
- Prior art date
Links
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2878—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/66—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a swap of domains, e.g. CH3-CH2, VH-CL or VL-CH1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
Abstract
The invention relates to new antibodies against BCMA, their manufacture and use. The antibodies are useful in treating plasma cell disorders.
Claims (31)
1. A monoclonal antibody specifically binding to human B cell maturation antigen (BCMA), wherein the antibody comprises a CDR1H of SEQ ID NO:21, a CDR2H of SEQ ID NO:22, a CDR3H of SEQ ID NO:17, a CDR1L of SEQ ID NO:27, a CDR2L of SEQ ID NO:28 and a CDR3L of SEQ ID NO:20.
2. A monoclonal antibody specifically binding to BCMA, wherein the antibody comprises a CDR1H of SEQ ID NO:21, a CDR2H of SEQ ID:22, a CDR3H of SEQ ID NO:17, a CDR1L of SEQ ID NO:25, a CDR2L of SEQ ID NO:26 and a CDR3L of SEQ ID NO:20.
3. The monoclonal antibody according to claim 1, comprising a VH region of SEQ ID NO:10 and a VL region of SEQ ID NO: 14.
4. The monoclonal antibody according to claim 2, comprising a VH region of SEQ ID NO:10 and a VL region of SEQ ID NO: 13.
5. A bispecific antibody specifically binding to BCMA and human CD3? (“CD3”), wherein the bispecific antibody comprises a CDR1H of SEQ ID NO:21, a CDR2H of SEQ ID NO:22, a CDR3H of SEQ ID NO:17, a CDR1L of SEQ ID NO:27, a CDR2L of SEQ ID NO:28 and a CDR3L of SEQ ID NO:20.
6. A bispecific antibody specifically binding to BCMA and CD3, wherein the bispecific antibody comprises a CDR1H of SEQ ID NO:21, a CDR2H of SEQ ID NO:22, a CDR3H of SEQ ID NO:17, a CDR1L of SEQ ID NO:25, a CDR2L of SEQ ID NO:26 and a CDR3L of SEQ ID NO:20.
7. The bispecific antibody according to claim 5, comprising a BCMA VH region of SEQ ID NO:10 and a VL region of SEQ ID NO:14.
8. The bispecific antibody according to claim 6, comprising a BCMA VH region of SEQ ID NO:10 and a VL region of SEQ ID NO:13.
9. The bispecific antibody according to any one of claims 5 to 8, wherein the bispecific antibody comprises a light chain and a heavy chain of an antibody specifically binding to CD3, wherein the variable domains VL and VH or the constant domains CL and CH1 are replaced by each other.
10. The bispecific antibody according to any one of claims 5 to 9, wherein that the variable domain VH of the anti-CD3 antibody portion (“CD3 VH”) comprises the heavy chain CDRs of SEQ ID NO: 1, 2 and 3 as heavy chain CDR1, CDR2 and CDR3, respectively, and the variable domain VL of the anti-CD3 antibody portion (“CD3 VL”) comprises the light chain CDRs of SEQ ID NO: 4, 5 and 6 as light chain CDR1, CDR2 and CDR3, respectively.
11. A bispecific antibody specifically binding to BCMA and CD3, comprising a) a first light chain and a first heavy chain of a first antibody according to any one of claims 1 to 4; and b) a second light chain and a second heavy chain of a second antibody which specifically binds to CD3, and wherein the variable domains VL and VH in the second light chain and second heavy chain of the second antibody are replaced by each other; and c) wherein in the constant domain CL of the first light chain under a) the amino acid at position 124 is substituted independently by lysine (K), arginine (R) or histidine (H) (numbering according to Kabat), and wherein in the constant domain CH1 of the first heavy chain under a) the amino acid at position 147 and the amino acid at position 213 are substituted independently by glutamic acid (E), or aspartic acid (D) (numbering according to EU Index of Kabat).
12. The bispecific antibody according to claim 11, comprising in addition a Fab fragment of said first antibody (“BCMA-Fab”) and in the constant domain CL of said BCMA-Fab the amino acid at position 124 is substituted independently by lysine (K), arginine (R) or histidine (H) (numbering according to Kabat), and wherein in the constant domain CH1 of said BCMA-Fab the amino acid at position 147 and the amino acid at position 213 are substituted independently by glutamic acid (E), or aspartic acid (D) (numbering according to EU Index of Kabat).
13. A bispecific antibody specifically binding to BCMA and CD3, comprising: a) a first light chain and a first heavy chain of a first antibody according to any one of claims 1 to 4; and b) a second light chain and a second heavy chain of a second antibody which specifically binds to CD3, and wherein the variable domains VL and VH in the second light chain and second heavy chain of the second antibody are replaced by each other; and wherein c) in the constant domain CL of the second light chain under b) the amino acid at position 124 is substituted independently by lysine (K), arginine (R) or histidine (H) (numbering according to Kabat), and wherein in the constant domain CH1 of the second heavy chain under b) the amino acid at position 147 and the amino acid at position 213 are substituted independently by glutamic acid (E), or aspartic acid (D) (numbering according to EU Index of Kabat).
14. The bispecific antibody according to any one of claims 5 to 13, comprising: a) not more than one Fab fragment of an anti-CD3 antibody portion, not more than two Fab fragments of an anti-BCMA antibody portion and not more than one Fc part; b) an Fc part linked with its N-terminus to the C-terminus of said CD3 antibody Fab fragment and to the C-terminus of one of said BCMA antibody Fab fragments; and/or c) a second Fab fragment of said anti-BCMA antibody portion linked with its C-terminus to the N-terminus of the CD3 antibody portion of said bispecific antibody.
15. The bispecific antibody according to claim 14, wherein the VL domain of said anti-CD3 antibody Fab fragment is linked to the CH1 domain of said second anti-BCMA antibody Fab fragment.
16. A bispecific antibody specifically binding to BCMA and to CD3, comprising a heavy and light chain set consisting of polypeptides SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:53, and two copies of SEQ ID NO:54.
17. A bispecific antibody specifically binding to BCMA and to CD3, comprising a heavy and light chain set consisting of polypeptides SEQ ID NO:48, SEQ ID NO:55, SEQ ID NO:56, and two copies of SEQ ID NO:57.
18. A multispecific antibody specifically binding to BCMA, wherein the antibody comprises a CDR1H of SEQ ID NO:21, a CDR2H of SEQ ID NO:22, a CDR3H of SEQ ID NO:17, a CDR1L of SEQ ID NO:27, a CDR2L of SEQ ID NO:28 and a CDR3L of SEQ ID NO:20.
19. A multispecific antibody specifically binding to BCMA, wherein the antibody comprises a CDR1H of SEQ ID NO:21, a CDR2H of SEQ ID NO:22, a CDR3H of SEQ ID NO:17, a CDR1L of SEQ ID NO:25, a CDR2L of SEQ ID NO:26 and a CDR3L of SEQ ID NO:20.
20. The multispecific antibody according to claim 18 or claim 19, wherein the multispecific antibody is a trispecific antibody.
21. A method for the preparation of an antibody according to any one of claims 1 to 20 comprising the steps of: a) transforming a host cell with vectors comprising nucleic acid molecules encoding the light chain and heavy chain of an antibody according to any one of claims 1 to 20, b) culturing the host cell under conditions that allow synthesis of said antibody molecule; and c) recovering said antibody molecule from said culture.
22. A pharmaceutical composition comprising an antibody according to any one of claims 1 to 20 and a pharmaceutically acceptable excipient.
23. Use of an antibody according to any one of claims 1 to 20 in the manufacture of a medicament for the treatment of plasma cell disorders.
24. Use of an antibody according to any one of claims 1 to 20 in the manufacture of a medicament for the treatment of multiple myeloma or systemic lupus erythematosus or plasma cell leukemia or AL- amyloidosis.
25. An antigen binding portion of an antibody specifically binding to BCMA, wherein the antigen binding portion comprises a CDR1H of SEQ ID NO:21, a CDR2H of SEQ ID NO:22, a CDR3H of SEQ ID NO:17, a CDR1L of SEQ ID NO:27, a CDR2L of SEQ ID NO:28 and a CDR3L of SEQ ID NO:20.
26. An antigen binding portion of an antibody specifically binding to BCMA, wherein the antigen binding portion comprises a CDR1H of SEQ ID NO:21, a CDR2H of SEQ ID NO:22, a CDR3H of SEQ ID NO:17, a CDR1L of SEQ ID NO:25, a CDR2L of SEQ ID NO:26 and a CDR3L of SEQ ID NO:20.
27. A chimeric antigen receptor (CAR), wherein the CAR comprises an antigen recognition moiety directed against BCMA and a T-cell activation moiety, wherein the antigen recognition moiety is a monoclonal antibody or antibody fragment according to any one of claims 1 to 4.
28. An isolated cell comprising vectors comprising nucleic acid molecules encoding an antibody according to any one of claims 1 to 20.
29. An antibody-drug conjugate, wherein the antibody specifically binds to BCMA and comprises a CDR1H of SEQ ID NO:21, a CDR2H of SEQ ID NO:22, a CDR3H of SEQ ID NO:17, a CDR1L of SEQ ID NO:27, a CDR2L of SEQ ID NO:28 and a CDR3L of SEQ ID NO:20.
30. An antibody-drug conjugate, wherein the antibody specifically binds to BCMA and comprises a CDR1H of SEQ ID NO:21, a CDR2H of SEQ ID NO:22, a CDR3H of SEQ ID NO:17, a CDR1L of SEQ ID NO:25, a CDR2L of SEQ ID NO:26 and a CDR3L of SEQ ID NO:20.
31. The antibody-drug conjugate according to claim 29 or claim 30, wherein the antibody is conjugated with a therapeutic agent, a cytotoxic agent or a radiolabel.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15179549 | 2015-08-03 | ||
| PCT/EP2016/068549 WO2017021450A1 (en) | 2015-08-03 | 2016-08-03 | Monoclonal antibodies against bcma |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ739252A NZ739252A (en) | 2023-12-22 |
| NZ739252B2 true NZ739252B2 (en) | 2024-03-26 |
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