# US 12,006,367 B2 · CD3/CD38 T cell retargeting hetero-dimeric immunoglobulins and methods of their production

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- Number: US 12,006,367 B2
- Document ID: US12006367B2
- Status: Granted
- Kind: B2
- Application number: 17/806,218
- Filed: 2022-06-09
- Published: 2023-03-02
- Granted: 2024-06-11
- Earliest claimed: 2014-11-04
- Assignees: Ichnos Sciences SA
- Applicants: Ichnos Sciences SA
- Inventors: Romain Ollier; Samuel Hou; Rami Lissilaa; Darko Skegro; Jonathan Back
- Web page: https://patentgrep.com/patent/US12006367B2

## CPC

- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- A61P 35/00: Antineoplastic agents
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/524: CH2 domain
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

The present invention relates to hetero-dimeric immunoglobulins that target both a component of the human CD3 antigen and a component of the human CD38 antigen and methods of making the same. The present invention also relates to antibodies which bind to the human CD38 antigen and derivatives thereof for use as therapeutic or diagnostic reagents and methods of making the same.

## Claims

### Claim 1

An antibody or fragment thereof that binds to human CD38 comprising a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 25 or SEQ ID NO: 208, and a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 26 or SEQ ID NO: 209, and a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 27 or SEQ ID NO: 210; and comprising a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 211 or SEQ ID NO: 214, and a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 29 or SEQ ID NO: 212, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 213.

### Claim 2 (depends on 1)

The antibody or fragment thereof of claim 1, wherein the antibody or fragment thereof is a murine antibody, chimeric antibody or a humanized antibody.

### Claim 3 (depends on 1)

The antibody or fragment thereof of claim 1, wherein the antibody or fragment thereof comprises a heavy chain variable region sequence comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 52, SEQ ID NO: 58, and SEQ ID NO: 60 or a sequence at least 80% identical to the non-CDR region of said heavy chain variable region sequences and/or wherein the antibody or fragment thereof comprises a light chain variable region sequence comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 55, SEQ ID NO: 59, and SEQ ID NO: 61 or a sequence at least 80% identical to the non-CDR region of any one of said light chain variable region sequences.

### Claim 4 (depends on 1)

The antibody or fragment thereof of claim 1, wherein the antibody or fragment thereof comprises a heavy chain sequence comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 73, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 145, SEQ ID NO: 147, and SEQ ID NO: 149 or a sequence at least 80% identical to the non-CDR region of said heavy chain variable region sequences and/or wherein the antibody or fragment thereof comprises a light chain region sequence comprising the amino acid sequence elected from the group consisting of SEQ ID NO: 74, SEQ ID NO: 77, SEQ ID NO: 146, SEQ ID NO: 148, and SEQ ID NO: 150 or a sequence at least 80% identical to the non-CDR region of any one of said light chain variable region sequences.

### Claim 5 (depends on 1)

The antibody or fragment thereof of claim 1, wherein said antibody or fragment comprises human heavy and/or light chain constant regions and wherein the human heavy constant region is selected from the group consisting of human immunoglobulins consisting of IGHG1, non fucosylated IGHG1, and IGHG4.

### Claim 6 (depends on 1)

A composition comprising the antibody or fragment thereof of claim 1 and a pharmaceutically acceptable carrier.

### Claim 7 (depends on 1)

An immunoconjugate comprising the antibody or fragment thereof of claim 1, linked to a therapeutic agent.

### Claim 8 (depends on 1)

A method of treating a disease selected from the group consisting of malignant hematological diseases, including multiple myeloma, B-cell chronic lymphocytic leukaemia, B-cell acute lymphocytic leukaemia, Waldenstrom's macroglobulinemia, primary systemic amyloidosis, mantle-cell lymphoma, pro-lymphocytic/myelocytic leukaemia, acute myeloid leukaemia, chronic myeloid leukaemia, follicular lymphoma, NK-cell leukaemia, and plasma-cell leukaemia comprising administering the antibody or fragment thereof of claim 1.

### Claim 9 (depends on 1)

The antibody or fragment thereof of claim 1, wherein said antibody binds both human and cynomolgus CD38.