# US 10,870,694 B2 · Composition and methods of treating B cell disorders

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- Number: US 10,870,694 B2
- Document ID: US10870694B2
- Status: Granted
- Kind: B2
- Application number: 16/330,188
- Filed: 2017-09-05
- Published: 2019-09-12
- Granted: 2020-12-22
- Earliest claimed: 2016-09-02
- Assignees: Dana-Farber Cancer Institute, Inc.
- Applicants: Dana-Farber Cancer Institute, Inc.
- Inventors: Wayne A. Marasco
- Web page: https://patentgrep.com/patent/US10870694B2

## CPC

- C07K 16/18: against material from animals or humans
- A61K 39/39566: {against immunoglobulins, e.g. anti-idiotypic antibodies}
- A61P 35/02: specific for leukemia
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/4241: {against anti-human or anti-animal Ig}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/35: Valency
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/734: Complement-dependent cytotoxicity [CDC]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- 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 comprises methods of using a humanized monoclonal antibody that binds to the human immunoglobulin heavy chain variable region germline gene VH1-69 to treat B-cell disorders.

## Claims

### Claim 1

A method of selectively killing a B-cell expressing a IGHV1-69 BCR comprising contacting the B-cell with a chimeric antigen receptor comprising an huG6 antibody.

### Claim 2 (depends on 1)

The method of claim 1, wherein said antibody is monovalent or bivalent.

### Claim 3 (depends on 1)

The method of claim 1, wherein said antibody is a single chain antibody.

### Claim 4 (depends on 1)

The method of claim 1, wherein the huG6 antibody comprises:
a humanized heavy chain with three CDRs comprising an amino acid sequence GYTFTSYW (SEQ ID NO: 1); VSPGNSDT (SEQ ID NO: 2); and
TRSRYGNNALDY (SEQ ID NO: 3); and a humanized light chain with three CDRs that include an amino acid sequence selected from the group consisting of the amino acid sequences of QGISSNIVW (SEQ ID NO: 4); HGT (SEQ ID NO:
5); and VQYSQFPPT (SEQ ID NO: 6).

### Claim 5 (depends on 1)

The method of claim 1, wherein the huG6 antibody comprises:
a. a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 14 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:8;
b. a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 10 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 12; or
c. a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 14 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:12.

### Claim 6 (depends on 1)

The method of claim 1, wherein the chimeric antigen receptor is contacted with the B-cell prior to, concurrently with, or subsequent to contacting the B-cell with a chemotherapeutic agent.

### Claim 7

A method of selectively killing a B-cell expressing a IGHV1-69 BCR comprising administering to a subject in need thereof a chimeric antigen receptor comprising an huG6 antibody.

### Claim 8 (depends on 7)

The method of claim 7, wherein the subject has a cancer, an autoimmune disorder or an inflammatory disorder.

### Claim 9 (depends on 7)

The method of claim 7, wherein the subject has chronic lymphocytic leukemia of B-cell phenotype (B-CLL), thrombotic thrombocytopenic purpura (TPP), idiopathic thrombocytopenia purpura (ITP) or cryoglobulinemia.

### Claim 10 (depends on 7)

The method of claim 7, wherein said chimeric antigen receptor is administered prior to, concurrently with, or subsequent to the administration of a chemotherapeutic agent.

### Claim 11

A method of selectively killing a B-cell expressing a IGHV1-69 BCR comprising contacting the B-cell with a chimeric antigen receptor comprising an huG6 antibody, wherein said chimeric antigen receptor comprising an huG6 antibody is contacted with the B-cell prior to, concurrently with, or subsequent to contacting the B-cell with a chemotherapeutic agent.

### Claim 12

A method of selectively killing a B-cell expressing a IGHV1-69 BCR comprising administering to a subject in need thereof a chimeric antigen receptor comprising an huG6 antibody, wherein said chimeric antigen receptor comprising an huG6 antibody is administered to, concurrently with, or subsequent to the administration of a chemotherapeutic agent.
