Amino Acid Sequences Directed Against the Melanocortin 4 Receptor and Polypeptides Comprising the Same for the Treatment of MC4R-Related Diseases and Disorders

{
  "publication_number": "US2026103529A1",
  "country": "US",
  "kind": "A1",
  "title": "Amino Acid Sequences Directed Against the Melanocortin 4 Receptor and Polypeptides Comprising the Same for the Treatment of MC4R-Related Diseases and Disorders",
  "abstract": "The present invention relates to agonist VHH that are specific for (as defined herein) melanocortin 4 receptor (“MC4R”), as well as to proteins and polypeptides, that comprise or essentially consist of one or more such VHH sequences and medical uses to reduce body weight.",
  "claims": [
    "1. Nanobody in which: CDR1 is chosen from the group consisting of: a) the amino acid sequences of SEQ ID NO's: 134 to 141 and 210 to 225; b) amino acid sequences that have at least 80% amino acid identity with at least one of the amino acid sequences of SEQ ID NO's: 134 to 141 and 210 to 225; and c) amino acid sequences that have 3, 2, or 1 amino acid difference with at least one of the amino acid sequences of SEQ ID NO's: 134 to 141 and 210 to 225; and CDR2 is chosen from the group consisting of: d) the amino acid sequences of SEQ ID NO's: 150 to 157 and 242 to 257; e) amino acid sequences that have at least 80% amino acid identity with at least one of the amino acid sequences of SEQ ID NO's: 150 to 157 and 242 to 257; and f) amino acid sequences that have 3, 2, or 1 amino acid difference with at least one of the amino acid sequences of SEQ ID NO's: 150 to 157 and 242 to 257; and CDR3 sequence is an amino acid sequence comprising 9, 10, 11, 12 or 13 amino acid residues and comprising (i) at least one arginine residue (R) that is capable of interacting with the Glu100 and/or Asp126 residues of MC4R; and (ii) at least one arginine residue (R) that is capable of interacting with the Ser188 and/or Asp189 residues of MC4R. 2. The nanobody of claim 1, in which CDR3 is the amino acid sequence RTGRIVRPLDY (SEQ ID NO: 168) or an analog thereof. 3. The nanobody of claim 1, which is chosen from the group consisting of SEQ ID NO's: 185 to 189 or from the group consisting of amino acid sequences that have more than 80%, sequence identity with at least one of the amino acid sequences of SEQ ID NO's: 185 to 189. 4. The nanobody of claim 1, wherein the nanobody is humanized. 5. The nanobody of claim 1, wherein the nanobody is an MC4R agonist. 6. The nanobody of claim 1, wherein the nanobody has the amino acid sequence of SEQ ID NO:189. 7. A compound, composition, pharmaceutical composition, construct, protein, or polypeptide, comprising at least one nanobody of claim 1. 8. The compound, composition, pharmaceutical composition, construct, protein, or polypeptide of claim 7, comprising two nanobodies of claim 1 linked to an Fc portion. 9. (canceled) 10. (canceled) 11. The nanobody of claim 1, wherein the nanobody specifically binds to MC4R. 12. The nanobody of claim 1, wherein CDR3 comprises at least two amino acid residues that interact with the Gln43 and/or Gln 269 residues of MC4R 13. The nanobody of claim 3, which is chosen from the group consisting of amino acid sequences that have more than 90%, sequence identity with at least one of the amino acid sequences of SEQ ID NO's: 185 to 189. 14. The nanobody of claim 3, which is chosen from the group consisting of amino acid sequences that have more than 95%, sequence identity with at least one of the amino acid sequences of SEQ ID NO's: 185 to 189. 15. The nanobody of claim 3, which is chosen from the group consisting of amino acid sequences that have more than 95%, sequence identity with at least one of the amino acid sequences of SEQ ID NO's: 185 to 189. 16. A method of binding MC4R is a subject, the method comprising administering to the subject the compound, composition, pharmaceutical composition, construct, protein, or polypeptide of claim 7. 17. The method of claim 16, wherein the subject suffers from an MC4R related disease or disorder."
  ],
  "description_excerpt": "The present invention relates to amino acid sequences that are directed against (as defined herein) melanocortin 4 receptor (“MC4R”), as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences (also referred to herein as “amino acid sequences of the invention”, “compounds of the invention”, and “polypeptides of the invention” and, in the case of a polypeptide or protein construct “constructs of the invention”, respectively).\n\nThe invention also relates to nucleic acids encoding such amino acid sequences and polypeptides (also referred to herein as “nucleic acids of the invention” or “nucleotide sequences of the invention”); to methods for preparing such amino acid sequences and polypeptides; to host cells expressing or capable of expressing such amino acid sequences or polypeptides; to compositions, and in particular to pharmaceutical compositions, that comprise such amino acid sequences, polypeptides, nucleic acids and/or host cells; and to uses of such amino acid sequences or polypeptides, nucleic acids, host cells and/or compositions, in particular for prophylactic, therapeutic or diagnostic purposes, such as the prophylactic, therapeutic or diagnostic purposes mentioned herein.\n\nOther aspects, embodiments, advantages and applications of the invention will become clear from the further description herein.\n\nThe melanocortin 4 receptor (“MC4R”) is a Class A GPCR. It is an integral membrane protein with a short N-terminal domain and tiny extracellular loops.",
  "cpc": [
    "C07K 16/2869",
    "A61K 2039/505",
    "C07K 2317/24",
    "C07K 2317/52",
    "C07K 2317/565",
    "C07K 2317/569",
    "C07K 2317/75"
  ],
  "assignees": [
    "Confo Therapeutics NV"
  ],
  "inventors": [
    "Christel Menet",
    "Maarten Van Roy",
    "Toon Laeremans",
    "Rosa Barrocco",
    "Stephanie Staelens",
    "Veli-Pekka Jaakola",
    "Kamila Skieterska",
    "Thomas Fontaine"
  ],
  "filing_date": "2023-10-17",
  "publication_date": "2026-04-16",
  "priority_date": "2022-10-18",
  "application_number": "US-202319122123-A",
  "cited_by_count": 0
}