# US 12,180,298 B2 · Heavy chain antibodies binding to PSMA > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,180,298 B2 - Document ID: US12180298B2 - Status: Granted - Kind: B2 - Application number: 17/601,417 - Filed: 2020-04-03 - Published: 2022-06-23 - Granted: 2024-12-31 - Earliest claimed: 2019-04-05 - Assignees: TeneoBio, Inc. - Applicants: Teneobio, Inc. - Inventors: Wim van Schooten; Starlynn Clarke; Kevin Dang; Ben Buelow - Web page: https://patentgrep.com/patent/US12180298B2 ## CPC - C07K 16/3069: {Reproductive system, e.g. ovaria, uterus, testes, prostate} - A61P 35/00: Antineoplastic agents - C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex} - A61K 2039/505: {comprising antibodies} - 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 2317/565: Complementarity determining region [CDR] - C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody® - C07K 2317/60: characterized by non-natural combinations of immunoglobulin fragments - 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) - 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 Anti-PSMA heavy chain antibodies are disclosed, along with methods of making such antibodies, compositions, including pharmaceutical compositions, comprising such antibodies, and their use to treat disorders that are characterized by the expression of PSMA. ## Claims ### Claim 1 An antigen-binding region of an anti-PSMA heavy chain antibody, comprising a CDR1 sequence of SEQ ID NO: 2, a CDR2 sequence of SEQ ID NO: 11, and a CDR3 sequence of SEQ ID NO: 18. ### Claim 2 (depends on 1) The antigen-binding region according to claim 1, comprising a CDR1 sequence of SEQ ID NO: 2, a CDR2 sequence of SEQ ID NO: 11, and a CDR3 sequence of SEQ ID NO: 18 in a human VH framework. ### Claim 3 (depends on 1) The antigen-binding region according to claim 1, comprising a CDR1 sequence of SEQ ID NO: 2, a CDR2 sequence of SEQ ID NO: 11, and a CDR3 sequence of SEQ ID NO: 18 in a monovalent configuration. ### Claim 4 (depends on 1) The antigen-binding region according to claim 1, comprising a heavy chain variable region sequence of SEQ ID NO: 25. ### Claim 5 An antibody comprising an antigen-binding region of an anti-PSMA heavy chain antibody, wherein the antigen-binding region comprises a CDR1 sequence of SEQ ID NO: 2, a CDR2 sequence of SEQ ID NO: 11, and a CDR3 sequence of SEQ ID NO: 18. ### Claim 6 (depends on 5) The antibody according to claim 5, wherein the antigen-binding region comprises a CDR1 sequence of SEQ ID NO: 2, a CDR2 sequence of SEQ ID NO: 11, and a CDR3 sequence of SEQ ID NO: 18 in a human VH framework. ### Claim 7 (depends on 5) The antibody according to claim 5, wherein the antigen-binding region comprises a CDR1 sequence of SEQ ID NO: 2, a CDR2 sequence of SEQ ID NO: 11, and a CDR3 sequence of SEQ ID NO: 18 in a monovalent configuration. ### Claim 8 (depends on 5) The antibody according to claim 5, wherein the antigen-binding region comprises a heavy chain variable region sequence of SEQ ID NO: 25. ### Claim 9 (depends on 5) The antibody according to claim 5, wherein the antibody is a bispecific antibody. ### Claim 10 (depends on 9) The antibody according to claim 9, wherein the antibody further binds to a CD3 protein. ### Claim 11 (depends on 9) The antibody according to claim 9, further comprising a CD3-binding heavy chain variable region that is paired with a light chain variable region. ### Claim 12 (depends on 11) The antibody according to claim 11, wherein the CD3-binding heavy chain variable region comprises a CDR1 sequence of SEQ ID NO: 59, a CDR2 sequence of SEQ ID NO: 60, and a CDR3 sequence of SEQ ID NO: 61. ### Claim 13 (depends on 11) The antibody according to claim 11, wherein the CD3-binding heavy chain variable region comprises heavy chain variable region sequence of SEQ ID NO: 65. ### Claim 14 (depends on 11) The antibody according to claim 11, wherein the light chain variable region comprises a CDR1 sequence of SEQ ID NO: 62, a CDR2 sequence of SEQ ID NO: 63, and a CDR3 sequence of SEQ ID NO: 64. ### Claim 15 (depends on 11) The antibody according to claim 11, wherein the light chain variable region comprises a light chain variable region sequence of SEQ ID NO: 66. ### Claim 16 (depends on 10) The antibody according to claim 10, wherein the antibody is a three-chain antibody-like molecule. ### Claim 17 A three-chain antibody-like molecule that binds to a CD3 protein and a PSMA protein, comprising: a first polypeptide comprising the sequence of SEQ ID NO: 86; a second polypeptide comprising the sequence of SEQ ID NO: 87; and a third polypeptide comprising the sequence of SEQ ID NO: 88, 89, 90, 91, 92, or 93. ### Claim 18 (depends on 17) The three-chain antibody-like molecule according to claim 17, wherein the third polypeptide comprises SEQ ID NO: 88. ### Claim 19 (depends on 10) A pharmaceutical composition comprising: the antibody according to claim 10; and a pharmaceutically acceptable carrier. ### Claim 20 A three-chain antibody-like molecule comprising: (a) a PSMA-binding heavy chain variable region comprising: a CDR1 sequence of the formula G G S I S S X1 X2 Y X3 (SEQ ID NO: 67), wherein X1 is S or N; X2 is S or N; and X3 is Y or F; and a CDR2 sequence of the formula X4 X5 X6 S G X7 T (SEQ ID NO: 68), wherein X4 is I or V; X5 is D or Y; X6 is Y or D; and X7 is Y or S; and a CDR3 sequence of SEQ ID NO: 18; and (b) a CD3-binding heavy chain variable region that is paired with a light chain variable region, wherein: the CD3-binding heavy chain variable region comprises a CDR1 sequence of SEQ ID NO: 59, a CDR2 sequence of SEQ ID NO: 60, and a CDR3 sequence of SEQ ID NO: 61; and the light chain variable region comprises a CDR1 sequence of SEQ ID NO: 62, a CDR2 sequence of GAS, and a CDR3 sequence of SEQ ID NO: 64. ### Claim 21 (depends on 20) The three-chain antibody-like molecule of claim 20, wherein the PSMA-binding heavy chain variable region comprises a CDR1 sequence of any one of SEQ ID NOs: 1-3, a CDR2 sequence of any one of SEQ ID NOs: 11-13, and a CDR3 sequence of SEQ ID NO: 18. ### Claim 22 (depends on 20) The three-chain antibody-like molecule of claim 20, wherein the PSMA-binding heavy chain variable region comprises: a CDR1 sequence of SEQ ID NO: 1, a CDR2 sequence of SEQ ID NO: 11, and a CDR3 sequence of SEQ ID NO: 18; or a CDR1 sequence of SEQ ID NO: 1, a CDR2 sequence of SEQ ID NO: 12, and a CDR3 sequence of SEQ ID NO: 18; or a CDR1 sequence of SEQ ID NO: 2, a CDR2 sequence of SEQ ID NO: 11, and a CDR3 sequence of SEQ ID NO: 18; or a CDR1 sequence of SEQ ID NO: 3, a CDR2 sequence of SEQ ID NO: 13, and a CDR3 sequence of SEQ ID NO: 18. ### Claim 23 (depends on 20) The three-chain antibody-like molecule of claim 20, wherein the PSMA-binding heavy chain variable region comprises a CDR1 sequence of SEQ ID NO: 2, a CDR2 sequence of SEQ ID NO: 11, and a CDR3 sequence of SEQ ID NO: 18. ### Claim 24 (depends on 20) The three-chain antibody-like molecule of claim 20, wherein the PSMA-binding heavy chain variable region comprises a heavy chain variable region sequence of any one of SEQ ID NOs: 24-28. ### Claim 25 (depends on 20) The three-chain antibody-like molecule of claim 20, wherein the PSMA-binding heavy chain variable region comprises a heavy chain variable region sequence of SEQ ID NO: 25. ### Claim 26 (depends on 20) The three-chain antibody-like molecule of claim 20, wherein the CD3-binding heavy chain variable region comprises a heavy chain variable region sequence of SEQ ID NO: 65, and the light chain variable region comprises a light chain variable region sequence of SEQ ID NO: 66. ### Claim 27 (depends on 20) The three-chain antibody-like molecule of claim 20, wherein: the CD3-binding heavy chain variable region comprises a heavy chain variable region sequence of SEQ ID NO: 65; the light chain variable region comprises a light chain variable region sequence of SEQ ID NO: 66; and the PSMA-binding heavy chain variable region comprises a heavy chain variable region sequence of any one of SEQ ID NOs: 24-28. ### Claim 28 (depends on 20) The three-chain antibody-like molecule of claim 20, wherein: the CD3-binding heavy chain variable region comprises a heavy chain variable region sequence of SEQ ID NO: 65; the light chain variable region comprises a light chain variable region sequence of SEQ ID NO: 66; and the PSMA-binding heavy chain variable region comprises a heavy chain variable region sequence of SEQ ID NO: 25.