# US 11,993,654 B2 · PD-1 binding domains > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,993,654 B2 - Document ID: US11993654B2 - Status: Granted - Kind: B2 - Application number: 17/710,243 - Filed: 2022-03-31 - Published: 2023-02-02 - Granted: 2024-05-28 - Earliest claimed: 2021-03-31 - Assignees: Merus N.V.; Incyte Corporation - Applicants: Merus N.V.; Incyte Corporation - Inventors: Simon Edward Plyte; Patrick Mayes; Horacio G. Nastri; Shaun M. Stewart; Rebecca A. Buonpane - Web page: https://patentgrep.com/patent/US11993654B2 ## CPC - C07K 16/2818: {against CD28 or CD152} - 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 2317/35: Valency - C07K 2317/522: CH1 domain - C07K 2317/524: CH2 domain - C07K 2317/526: CH3 domain - C07K 2317/53: Hinge - C07K 2317/565: Complementarity determining region [CDR] - 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: 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) ## Abstract The present disclosure relates to novel PD-1 binding domains that have a higher binding affinity for human PD-1 than a reference PD-1 binding domain. The PD-1 binding domains of the present disclosure further provide a comparable, or equal or higher, potency in blocking ligand binding to human PD-1 than a reference PD-1 antibody. The present disclosure further relates to binding moieties comprising such PD-1 binding domains. Also provided is a method for treating a disease, in particular a disease associated with a suppressed immune system, such as cancer, with a PD-1 binding domain or binding moiety of the present disclosure. The present disclosure further relates to nucleic acids encoding the heavy chain variable region of the PD-1 binding domains, and a vector and cell comprising such nucleic acid. ## Claims ### Claim 1 An anti-human PD-1 binding domain comprising a heavy chain variable region, wherein the heavy chain variable region comprises: a) heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 22, SEQ ID NO: 23 and SEQ ID NO: 24, respectively; b) heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 25, SEQ ID NO: 26, and SEQ ID NO: 27, respectively; c) heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30, respectively; d) heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 31, SEQ ID NO: 32, and SEQ ID NO: 33, respectively; e) heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 34, SEQ ID NO: 35, and SEQ ID NO: 36, respectively; f) heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 37, SEQ ID NO: 38, and SEQ ID NO: 39, respectively; g) heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 40, SEQ ID NO: 41, and SEQ ID NO: 42, respectively; h) heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 43, SEQ ID NO: 44, and SEQ ID NO: 45, respectively; or i) heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 46, SEQ ID NO: 47, and SEQ ID NO: 48, respectively. ### Claim 2 (depends on 1) The anti-human PD-1 binding domain according to claim 1, comprising a heavy chain variable region having an amino acid sequence as set forth in any one of SEQ ID NO: 1-9 or having at least 90% sequence identity thereto. ### Claim 3 (depends on 1) The anti-human PD-1 binding domain according to claim 1, comprising a heavy chain variable region having an amino acid sequence as set forth in any one of SEQ ID NO: 1-9. ### Claim 4 (depends on 1) The anti-human PD-1 binding domain according to claim 1, further comprising a light chain variable region, wherein the light chain variable region comprises a light chain CDR1 (LCDR1), light chain CDR2 (LCDR2), and light chain CDR3 (LCDR3), having an amino acid sequence as set forth in SEQ ID NO: 49, SEQ ID NO: 50, and SEQ ID NO: 51, respectively. ### Claim 5 (depends on 2) The anti-human PD-1 binding domain according to claim 2, further comprising a light chain variable region having an amino acid sequence as set forth in SEQ ID NO: 16, or having at least 90% sequence identity thereto. ### Claim 6 (depends on 4) The anti-human PD-1 binding domain according to claim 4, wherein the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 16, or having at least 90% sequence identity thereto. ### Claim 7 (depends on 3) The anti-human PD-1 binding domain according to claim 3, further comprising a light chain variable region having an amino acid sequence as set forth in SEQ ID NO: 16. ### Claim 8 (depends on 4) The anti-human PD-1 binding domain according to claim 4, further comprising a CH1 and CL region. ### Claim 9 (depends on 1) The anti-human PD-1 binding domain according to claim 1, wherein the heavy chain variable region comprises: a heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 22, SEQ ID NO: 23 and SEQ ID NO: 24, respectively; and further comprising a light chain variable region comprising a light chain CDR1 (LCDR1), light chain CDR2 (LCDR2), and light chain CDR3 (LCDR3), having an amino acid sequence as set forth in SEQ ID NO: 49, SEQ ID NO: 50, and SEQ ID NO: 51, respectively. ### Claim 10 (depends on 1) The anti-human PD-1 binding domain according to claim 1, wherein the heavy chain variable region comprises: a heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 25, SEQ ID NO: 26, and SEQ ID NO: 27, respectively; and further comprising a light chain variable region comprising a light chain CDR1 (LCDR1), light chain CDR2 (LCDR2), and light chain CDR3 (LCDR3), having an amino acid sequence as set forth in SEQ ID NO: 49, SEQ ID NO: 50, and SEQ ID NO: 51, respectively. ### Claim 11 (depends on 1) The anti-human PD-1 binding domain according to claim 1, wherein the heavy chain variable region comprises: a heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30, respectively; and further comprising a light chain variable region comprising a light chain CDR1 (LCDR1), light chain CDR2 (LCDR2), and light chain CDR3 (LCDR3), having an amino acid sequence as set forth in SEQ ID NO: 49, SEQ ID NO: 50, and SEQ ID NO: 51, respectively. ### Claim 12 (depends on 1) The anti-human PD-1 binding domain according to claim 1, wherein the heavy chain variable region comprises: a heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 31, SEQ ID NO: 32, and SEQ ID NO: 33, respectively; and further comprising a light chain variable region comprising a light chain CDR1 (LCDR1), light chain CDR2 (LCDR2), and light chain CDR3 (LCDR3), having an amino acid sequence as set forth in SEQ ID NO: 49, SEQ ID NO: 50, and SEQ ID NO: 51, respectively. ### Claim 13 (depends on 1) The anti-human PD-1 binding domain according to claim 1, wherein the heavy chain variable region comprises: a heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 34, SEQ ID NO: 35, and SEQ ID NO: 36, respectively; and further comprising a light chain variable region comprising a light chain CDR1 (LCDR1), light chain CDR2 (LCDR2), and light chain CDR3 (LCDR3), having an amino acid sequence as set forth in SEQ ID NO: 49, SEQ ID NO: 50, and SEQ ID NO: 51, respectively. ### Claim 14 (depends on 1) The anti-human PD-1 binding domain according to claim 1, wherein the heavy chain variable region comprises: a heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 37, SEQ ID NO: 38, and SEQ ID NO: 39, respectively; and further comprising a light chain variable region comprising a light chain CDR1 (LCDR1), light chain CDR2 (LCDR2), and light chain CDR3 (LCDR3), having an amino acid sequence as set forth in SEQ ID NO: 49, SEQ ID NO: 50, and SEQ ID NO: 51, respectively. ### Claim 15 (depends on 1) The anti-human PD-1 binding domain according to claim 1, wherein the heavy chain variable region comprises: a heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 40, SEQ ID NO: 41, and SEQ ID NO: 42, respectively; and further comprising a light chain variable region comprising a light chain CDR1 (LCDR1), light chain CDR2 (LCDR2), and light chain CDR3 (LCDR3), having an amino acid sequence as set forth in SEQ ID NO: 49, SEQ ID NO: 50, and SEQ ID NO: 51, respectively. ### Claim 16 (depends on 1) The anti-human PD-1 binding domain according to claim 1, wherein the heavy chain variable region comprises: a heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 43, SEQ ID NO: 44, and SEQ ID NO: 45, respectively; and further comprising a light chain variable region comprising a light chain CDR1 (LCDR1), light chain CDR2 (LCDR2), and light chain CDR3 (LCDR3), having an amino acid sequence as set forth in SEQ ID NO: 49, SEQ ID NO: 50, and SEQ ID NO: 51, respectively. ### Claim 17 (depends on 1) The anti-human PD-1 binding domain according to claim 1, wherein the heavy chain variable region comprises: a heavy chain CDR1 (HCDR1), heavy chain CDR2 (HCDR2), and heavy chain CDR3 (HCDR3), having an amino acid sequence as set forth in SEQ ID NO: 46, SEQ ID NO: 47, and SEQ ID NO: 48, respectively; and further comprising a light chain variable region comprising a light chain CDR1 (LCDR1), light chain CDR2 (LCDR2), and light chain CDR3 (LCDR3), having an amino acid sequence as set forth in SEQ ID NO: 49, SEQ ID NO: 50, and SEQ ID NO: 51, respectively. ### Claim 18 (depends on 4) A binding moiety, wherein the binding moiety comprises an anti-PD-1 binding domain as claimed in claim 4. ### Claim 19 (depends on 18) The binding moiety according to claim 18, wherein the binding moiety is a monospecific binding moiety. ### Claim 20 (depends on 4) A pharmaceutical composition comprising an effective amount of an anti-human PD-1 binding domain according to claim 4, and a pharmaceutically acceptable carrier.