# US 11,028,171 B2 · Bispecific antibody constructs for CDH3 and CD3 > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,028,171 B2 - Document ID: US11028171B2 - Status: Granted - Kind: B2 - Application number: 15/566,444 - Filed: 2016-04-18 - Published: 2018-05-24 - Granted: 2021-06-08 - Earliest claimed: 2015-04-17 - Assignees: Amgen Research (Munich) GmbH - Applicants: Amgen Research (Munich) GmbH - Inventors: Bertram Weiss; Ann-Lena Frisk; Ruprecht Zierz; Peter Kufer; Tobias Raum; Doris Rau; Jonas Anlahr; Ralf Lutterbüse; Lisa Nahrwold; Christoph Dahlhoff; Claudia Blümel; Patrick Hoffmann - Web page: https://patentgrep.com/patent/US11028171B2 ## CPC - C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex} - A61P 35/00: Antineoplastic agents - C07K 16/28: against receptors, cell surface antigens or cell surface determinants - C07K 16/3053: {Skin, nerves, brain} - A61K 2039/505: {comprising antibodies} - C07K 2317/31: multispecific - C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity - C07K 2317/56: variable (Fv) region, i.e. VH and/or VL - 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 2317/732: Antibody-dependent cellular cytotoxicity [ADCC] - C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value - 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 a bispecific antibody construct comprising a first human binding domain which binds to human CDH3 on the surface of a target cell and a second binding domain which binds to human CDS on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. ## Claims ### Claim 1 A bispecific single chain antibody construct comprising a first human binding domain which binds to an epitope cluster of human CDH3 and macaque CDH3 on the surface of a target cell; and a second binding domain which binds to human CD3 on the surface of a T cell, wherein the epitope cluster of human CDH3 is comprised within amino acid positions 291-363 (SEQ ID NO: 36) of human CDH3, and wherein the first binding domain comprises a VH region and a VL region selected from the group consisting of: a) a VH region comprising a CDR-H1 as depicted in SEQ ID NO: 169, a CDR-H2 as depicted in SEQ ID NO: 170, and a CDR-H3 as depicted in SEQ ID NO: 171, and a VL region comprising a CDR-L1 as depicted in SEQ ID NO: 172, a CDR-L2 as depicted in SEQ ID NO: 173, and a CDR-L3 as depicted in SEQ ID NO: 174; b) a VH region comprising a CDR-H1 as depicted in SEQ ID NO: 279, a CDR-H2 as depicted in SEQ ID NO: 280, and a CDR-H3 as depicted in SEQ ID NO: 281, and a VL region comprising a CDR-L1 as depicted in SEQ ID NO: 282, a CDR-L2 as depicted in SEQ ID NO: 283, and a CDR-L3 as depicted in SEQ ID NO: 284; c) a VH region comprising a CDR-H1 as depicted in SEQ ID NO: 289, a CDR-H2 as depicted in SEQ ID NO: 290, and a CDR-H3 as depicted in SEQ ID NO: 291, and a VL region comprising a CDR-L1 as depicted in SEQ ID NO: 292, a CDR-L2 as depicted in SEQ ID NO: 293, and a CDR-L3 as depicted in SEQ ID NO: 294; d) a VH region comprising a CDR-H1 as depicted in SEQ ID NO: 299, a CDR-H2 as depicted in SEQ ID NO: 300, and a CDR-H3 as depicted in SEQ ID NO: 301, and a VL region comprising a CDR-L1 as depicted in SEQ ID NO: 302, a CDR-L2 as depicted in SEQ ID NO: 303, and a CDR-L3 as depicted in SEQ ID NO: 304; e) a VH region comprising a CDR-H1 as depicted in SEQ ID NO: 309, a CDR-H2 as depicted in SEQ ID NO: 310, and a CDR-H3 as depicted in SEQ ID NO: 311, and a VL region comprising a CDR-L1 as depicted in SEQ ID NO: 312, a CDR-L2 as depicted in SEQ ID NO: 313, and a CDR-L3 as depicted in SEQ ID NO: 314. ### Claim 2 (depends on 1) The antibody construct according to claim 1, wherein the first binding domain binds to an epitope which is comprised within amino acid positions 291-327 (SEQ ID NO: 34) of human CDH3. ### Claim 3 (depends on 1) The antibody construct according to claim 1, wherein the first binding domain binds to an epitope which is comprised within amino acid positions 328-363 (SEQ ID NO: 35) of human CDH3. ### Claim 4 (depends on 3) The antibody construct according to claim 3, wherein the first binding domain also binds to an epitope which is comprised within amino acid positions 404-440 (SEQ ID NO: 390) of human CDH3. ### Claim 5 (depends on 1) The antibody construct according to claim 1, wherein the macaque CDH3 is Macaca fascicularis CDH3. ### Claim 6 (depends on 1) The antibody construct according to claim 1, wherein the first binding domain comprises a VH region comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 155, SEQ ID NO: 165, SEQ ID NO: 175, SEQ ID NO: 285, SEQ ID NO: 295, SEQ ID NO: 305, and SEQ ID NO: 315. ### Claim 7 (depends on 1) The antibody construct according to claim 1, wherein the first binding domain comprises a VL region comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 176, SEQ ID NO: 286, SEQ ID NO: 296, SEQ ID NO: 306, and SEQ ID NO: 316. ### Claim 8 (depends on 1) The antibody construct according to claim 1, wherein the first binding domain comprises a VH region and a VL region comprising a pair of amino acid sequences selected from the group consisting of SEQ ID NO: 175 and 176, SEQ ID NO: 285 and 286, SEQ ID NO: 295 and 296, SEQ ID NO: 305 and 306, and SEQ ID NO: 315 and 316. ### Claim 9 (depends on 1) The antibody construct according to claim 1, wherein the first binding domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 177, SEQ ID NO: 287, SEQ ID NO: 297, SEQ ID NO: 307, and SEQ ID NO: 317. ### Claim 10 (depends on 1) The antibody construct according to claim 1, wherein the second binding domain binds to human and Callithrix jacchus, Saguinus Oedipus or Saimiri sciureus CD3 Epsilon. ### Claim 11 (depends on 1) The antibody construct according to claim 1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 178, SEQ ID NO: 288, SEQ ID NO: 298, SEQ ID NO: 308, and SEQ ID NO: 318. ### Claim 12 (depends on 1) The antibody construct according to claim 1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 379, SEQ ID NO: 380, SEQ ID NO: 381, SEQ ID NO: 382, SEQ ID NO: 383, SEQ ID NO: 384, SEQ ID NO: 385, SEQ ID NO: 386, SEQ ID NO: 387, SEQ ID NO: 388, SEQ ID NO: 389, and SEQ ID NO: 425. ### Claim 13 (depends on 1) A pharmaceutical composition comprising the antibody construct according to claim 1. ### Claim 14 (depends on 1) A kit comprising the antibody construct according to claim 1 and a recipient.