# US 2013/0280280 A1 · Antigen binding proteins

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- Number: US 2013/0280280 A1
- Document ID: US20130280280A1
- Status: Published application
- Kind: A1
- Application number: 13/795,314
- Filed: 2013-03-12
- Published: 2013-10-24
- Earliest claimed: 2011-05-27
- Assignees: GlaxoSmithKline LLC
- Inventors: PAUL ALGATE; STEPHANIE JANE CLEGG; JENNIFER L. CRAIGEN; PAUL ANDREW HAMBLIN; ALAN PETER LEWIS; PATRICK MAYES; RADHA SHAH PARMAR; TREVOR ANTHONY KENNETH WATTAM
- Web page: https://patentgrep.com/patent/US20130280280A1

## CPC

- C07K 16/3061: {Blood cells}
- A61K 38/05: Dipeptides
- A61K 47/68031: {the drug being an auristatin}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61P 35/02: specific for leukemia
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/41: Glycosylation, sialylation, or fucosylation
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/77: Internalization into the cell
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention concerns antigen binding proteins and fragments thereof which specifically bind B Cell Maturation Antigen (BCMA), particularly human BCMA (hBCMA) and which inhibit the binding of BAFF and APRIL to the BCMA receptor. Further disclosed are pharmaceutical compositions, screening and medical treatment methods.

## Claims

### Claim 1

An immunoconjugate comprising an antibody and a cytotoxic agent wherein said antibody comprises a heavy chain variable region set forth in SEQ. ID. NO:23 and a light chain variable region set forth in SEQ. ID. NO:31 and wherein said cytotoxic agent is selected from monomethylauristatin E (MMAE) and monomethylauristatin F (MMAF).

### Claim 2 (depends on 1)

The immunoconjugate of claim 1 wherein the antibody is an IgG1 isotype.

### Claim 3 (depends on 1)

The immunoconjugate of claim 1 wherein the antibody binds BCMA with an affinity of stronger than 150 pM.

### Claim 4 (depends on 1)

The immunoconjugate claim 1 wherein the cytotoxic agent is covalently bound to said anti body.

### Claim 5 (depends on 1)

The immunoconjugate claim 1 wherein the cytotoxic agent is bound to said antibody via a linker.

### Claim 6 (depends on 5)

The immunoconjugate of claim 5 wherein said linker is a cleavable linker.

### Claim 7 (depends on 5)

The immunoconjugate of claim 5 wherein said linker is a non-cleavable linker.

### Claim 8 (depends on 5)

The immunoconjugate of claim 5 wherein the linker is selected from 6-maleimidocaproyl (MC), maleimidopropanoyl (MP), valine-citrulline (val-cit), alanine-phenylalanine (ala-phe), p-aminobenzyloxycarbonyl (PAB), N-Succinimidyl 4-(2-pyridylthio)pentanoate (SPP), N-succinimidyl 4-(N-maleimidomethyl)cyclohexane-1 carboxylate (SMCC), and N-Succinimidyl (4-iodo-acetyl)aminobenzoate (STAB).

### Claim 9 (depends on 1)

The immunoconjugate of claim 1 wherein said immnuoconjugate is engulfed by a tumor cell when contacted with a tumor cell.

### Claim 10 (depends on 1)

The immunoconjugate of claim 1 wherien said antibody is afucosylated.

### Claim 11 (depends on 1)

A pharmaceutical composition comprising the immunoconjugate of claim 1 and a pharmaceutically acceptable carrier.

### Claim 12 (depends on 1)

A method of treating a human patient afflicted with a B cell lymphoma comprising administering to said human a therapeutically affective amount of the immunoconjugate of claim 1.

### Claim 13 (depends on 12)

The method of claim 12 wherien the B cell lymphoma is selected from Multiple Myeloma (MM) and Chronic Lymphocytic Leukaemia (CLL).

### Claim 14

An immunoconjugate comprising an antibody and a cytoxic agent wherein said antibody comprises the heavy chain amino acid sequence set forth in SEQ ID NO:55 and the light chain amino acid sequence set forth in SEQ ID NO:63 and the cytotoxic agent is monomethylauristatin E (MMAE), wherein said MMAE is linked to said antibody via a valine-citrulline (val-cit) linker.

### Claim 15

An immunoconjugate comprising an antibody and a cytoxic agent wherein said antibody comprises the heavy chain amino acid sequence set forth in SEQ ID NO:55 and the light chain amino acid sequence set forth in SEQ ID NO:63 and the cytotoxic agent is monomethylauristatin F (MMAF), wherein said MMAF is linked to said antibody via a 6-maleimidocaproyl (mc) linker.
