# US 11,440,960 B2 · TIGIT antibodies, encoding nucleic acids and methods of using said antibodies in vivo

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- Number: US 11,440,960 B2
- Document ID: US11440960B2
- Status: Granted
- Kind: B2
- Application number: 16/623,929
- Filed: 2018-06-20
- Published: 2020-04-30
- Granted: 2022-09-13
- Earliest claimed: 2017-06-20
- Assignees: Kymab Limited
- Applicants: Kymab Limited
- Inventors: Joana de Abreu Carvalho; Rachael Jane Kimber; Jamie Ian Campbell; Nikole Sandy; Cassandra Van Krinks; Stephen John Arkinstall; Volker Germaschewski; Ian Kirby; Miha Kosmac; Thomas Gallagher; Matthew John McCourt; Richard Charles Alfred Sainson; Mohammed Hanif Ali; E-Chiang Lee; Stephen Douglas Gillies
- Web page: https://patentgrep.com/patent/US11440960B2

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 35/00: Antineoplastic agents
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/31: multispecific
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/75: Agonist effect on antigen
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/90: characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/00: Fusion polypeptide
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention relates to antibodies specific for one or more antigens, bispecific antibodies containing one or more domains with specificity to the target(s), and to immunocytokines. The present invention also provides methods of treatment, uses and pharmaceutical compositions comprising the antibodies, bispecific antibodies and immunocytokines.

## Claims

### Claim 1

An antibody or fragment that comprises one or more TIGIT binding sites, wherein each binding site specifically binds to TIGIT and comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; wherein:
(a) the VH domain comprises an amino acid sequence at least 85% identical to SEQ ID NO:603 and the VL domain comprises an amino acid sequence at least 85% identical to SEQ ID NO:613;
(b) the VH domain comprises an amino acid sequence at least 85% identical to SEQ ID NO:623 and the VL domain comprises an amino acid sequence at least 85% identical to SEQ ID NO:633;
(c) the VH domain comprises an amino acid sequence at least 85% identical to SEQ ID NO:643 and the VL domain comprises an amino acid sequence at least 85% identical to SEQ ID NO:653; or
(d) the VH domain comprises an amino acid sequence at least 85% identical to SEQ ID NO:663 and the VL domain comprises an amino acid sequence at least 85% identical to SEQ ID NO:673; and
wherein:
(i) the VH domain of the antibody or fragment comprises the CDRH3 sequence of SEQ ID NO:599 or 602, the CDRH2 sequence of SEQ ID NO:598 or 601, and the CDRH1 sequence of SEQ ID NO:597 or 600; and the VL domain of the antibody or fragment comprises the CDRL3 sequence of SEQ ID NO:609 or 612, the CDRL2 sequence of SEQ ID NO:608 or 611, and the CDRL1 sequence of SEQ ID NO:607 or 610;
(ii) the VH domain of the antibody or fragment comprises the CDRH3 sequence of SEQ ID NO:619 or 622, the CDRH2 sequence of SEQ ID NO:618 or 621, and the CDRH1 sequence of SEQ ID NO:617 or 620; and the VL domain of the antibody or fragment comprises the CDRL3 sequence of SEQ ID NO:629 or 632, the CDRL2 sequence of SEQ ID NO:628 or 631, and the CDRL1 sequence of SEQ ID NO:627 or 630;
(iii) the VH domain of the antibody or fragment comprises the CDRH3 sequence of SEQ ID NO:639 or 642, the CDRH2 sequence of SEQ ID NO:638 or 641, and the CDRH1 sequence of SEQ ID NO:637 or 640; and the VL domain of the antibody or fragment comprises the CDRL3 sequence of SEQ ID NO:649 or 652, the CDRL2 sequence of SEQ ID NO:648 or 651, and the CDRL1 sequence of SEQ ID NO:647 or 650; or
(iv) the VH domain of the antibody or fragment comprises the CDRH3 sequence of SEQ ID NO:659 or 662, the CDRH2 sequence of SEQ ID NO:658 or 661, and the CDRH1 sequence of SEQ ID NO:657 or 660; and the VL domain of the antibody or fragment comprises the CDRL3 sequence of SEQ ID NO:669 or 672, the CDRL2 sequence of SEQ ID NO:668 or 671, and the CDRL1 sequence of SEQ ID NO:667 or 670.

### Claim 2 (depends on 1)

The antibody or fragment of claim 1, comprising first and second copies of said VH domain and/or said VL domain.

### Claim 3 (depends on 1)

The antibody or fragment of claim 1, wherein the VH domain further comprises a heavy chain constant region, wherein the heavy chain constant region comprises a human IgG1 or IgG4 constant region; and wherein the VL domain further comprises a light chain constant region, wherein the light chain constant region comprises a human kappa or lambda constant region.

### Claim 4 (depends on 1)

The antibody or fragment of claim 1, wherein
(i) the VH domain is encoded by a nucleotide sequence that is derived from the recombination of a human VH gene segment, DH gene segment and JH gene segment, wherein the VH gene segment is selected from IGHV3-11, IGHV3-15, IGHV3-20, IGHV3-9, and IGHV4-4; and
(ii) the VL domain is encoded by a nucleotide sequence that is derived from the recombination of a human VL gene segment and JL gene segment, wherein the VL gene segment is selected from IGKV1-39, IGKV1D-39, IGKV1-5, IGLV3-1, IGKV2-28, and IGLV3-10.

### Claim 5 (depends on 4)

The antibody or fragment according to claim 4, wherein the DH gene segment is a human gene segment selected from IGHD3-10, IGHD3-9, IGHD6-13, IGHD6-19, IGHD1-14, IGHD2-21, IGHD4-17, and IGHD4-23 and/or the JH gene segment is a human gene segment selected from IGHJ4, IGHJ5, and IGHJ6.

### Claim 6 (depends on 4)

The antibody or fragment according to claim 4, wherein the VL domain is a Vκ and the JL gene segment is a human gene segment selected from IGKJ2*04 and IGKJ4*01; or the VL domain is a Vλ and the JL gene segment is a human gene segment selected from IGLJ1*01, IGLJ2*01, and IGLJ3*02.

### Claim 7 (depends on 1)

The antibody or fragment of claim 1, which specifically binds to a human TIGIT comprising SEQ ID NO:540 or 544, a cynomolgus TIGIT comprising SEQ ID NO:547 or 549, and/or a mouse TIGIT comprising SEQ ID NO:556 or 559.

### Claim 8 (depends on 1)

A nucleic acid that encodes a VH domain and/or a VL domain of the antibody or fragment of claim 1.

### Claim 9 (depends on 8)

A vector comprising the nucleic acid of claim 8.

### Claim 10 (depends on 9)

An isolated host cell comprising the vector of claim 9.

### Claim 11 (depends on 1)

A pharmaceutical composition comprising the antibody or fragment of claim 1 and a pharmaceutically acceptable excipient, diluent, or carrier.

### Claim 12 (depends on 11)

The pharmaceutical composition of claim 11, in combination with a further therapeutic agent.

### Claim 13 (depends on 1)

A method of inhibiting TIGIT-mediated suppression of T-cells and/or NK cells that express TIGIT in a subject, comprising administering an effective amount of the antibody or fragment of claim 1.

### Claim 14 (depends on 1)

A method of increasing T- and/or NK cell proliferation, cytokine production by T- and/or NK cells, or degranulation of tumour antigen-specific CD8+ T cells and/or TIL CD8+ T cells in a subject, comprising administering an effective amount of the antibody or fragment of claim 1.