# US 12,180,268 B2 · Immunoglobulin variable domains > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,180,268 B2 - Document ID: US12180268B2 - Status: Granted - Kind: B2 - Application number: 15/311,564 - Filed: 2015-05-13 - Published: 2017-05-04 - Granted: 2024-12-31 - Earliest claimed: 2014-05-16 - Assignees: Ablynx N.V.; Sanofi - Applicants: Ablynx N.V.; Sanofi - Inventors: Marie-Ange Buyse; Carlo Boutton - Web page: https://patentgrep.com/patent/US12180268B2 ## CPC - C07K 16/18: against material from animals or humans - A61P 37/02: Immunomodulators - C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies - C07K 16/24: against cytokines, lymphokines or interferons - C07K 16/241: {Tumor Necrosis Factors} - C07K 16/244: {Interleukins [IL]} - C07K 16/28: against receptors, cell surface antigens or cell surface determinants - C07K 16/2863: {against receptors for growth factors, growth regulators} - C07K 16/2866: {against receptors for cytokines, lymphokines, interferons} - C07K 16/2875: {against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 (against NGF C07K16/22, against TNF C07K16/241)} - C07K 16/30: from tumour cells - C07K 16/32: against translation products of oncogenes - C07K 16/42: against immunoglobulins - C07K 16/4291: {against IgE} - C07K 2317/22: from camelids, e.g. camel, llama or dromedary - C07K 2317/31: multispecific - C07K 2317/35: Valency - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/567: Framework region [FR] - C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody® - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - C07K 2319/00: Fusion polypeptide - C07K 2319/31: fusions, other than Fc, for prolonged plasma life, e.g. albumin - 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 ## Abstract VH domain, in which: (i) the amino acid residue at position 1 12 is one of K or Q; and/or (ii) the amino acid residue at position 89 is T; and/or (iii) the amino acid residue at position 89 is L and the amino acid residue at position 1 10 is one of K or Q; and (iv) in each of cases (i) to (hi), the amino acid at position 1 1 is preferably V; and in which said VH domain contains a C-terminal extension (X)n, in which n is 1 to 10, preferably 1 to 5, such as 1, 2, 3, 4 or 5 (and preferably 1 or 2, such as 1); and each X is an (preferably naturally occurring) amino acid residue that is independently chosen, and preferably independently chosen from the group consisting of alanine (A), glycine (G), valine (V), leucine (L) or isoleucine (I). ## Claims ### Claim 1 A heavy chain immunoglobulin single variable domain (ISVD) in which the amino acid residue at Kabat position 89 is L and the amino acid at Kabat position 11 is V, wherein the heavy chain ISVD specifically binds to OX40L and comprises four framework regions (FW1, FW2, FW3 and FW4) and three CDRs (CDR1, CDR2 and CDR3), wherein CDR1 comprises the sequence of SEQ ID NO: 209; CDR2 comprises the sequence of SEQ ID NO: 210; and CDR3 comprises the sequence of SEQ ID NO: 211. ### Claim 2 (depends on 1) The heavy chain ISVD according to claim 1, wherein the C-terminal end of the heavy chain ISVD comprises an amino acid sequence selected from the group consisting of: VTVSS (SEQ ID NO:76), VKVSS (SEQ ID NO: 95), and VQVSS (SEQ ID NO: 96). ### Claim 3 (depends on 1) A fusion polypeptide comprising a heavy chain ISVD according to claim 1 fused to an additional heavy chain ISVD. ### Claim 4 (depends on 3) The fusion polypeptide according to claim 3, wherein the additional heavy chain ISVD specifically binds to serum albumin. ### Claim 5 (depends on 4) The fusion polypeptide according to claim 4, wherein the additional heavy chain ISVD has at least 90% sequence identity with Alb-8 (SEQ ID NO:46) or Alb-23 (SEQ ID NO:61). ### Claim 6 (depends on 4) The fusion polypeptide according to claim 4, wherein the additional heavy chain ISVD comprises a CDR1, CDR2, and CDR3 in which: CDR1 comprises the amino acid sequence SFGMS (SEQ ID NO:41); CDR2 comprises the amino acid sequence SISGSGSDTLYADSVKG (SEQ ID NO:42); and CDR3 comprises the amino acid sequence GGSLSR (SEQ ID NO:43). ### Claim 7 (depends on 1) The heavy chain ISVD according to claim 1, in which: the amino acid residue at Kabat position 14 is selected from the group consisting of A or P; the amino acid residue at Kabat position 41 is selected from the group consisting of A or P; the amino acid residue at Kabat position 108 is selected from the group consisting of Q or L; and the amino acid residue at Kabat position 110 is selected from the group consisting of T or Q. ### Claim 8 (depends on 3) A composition comprising a fusion polypeptide according to claim 3, and further comprising at least one pharmaceutically acceptable carrier, diluent or excipient. ### Claim 9 (depends on 1) The heavy chain ISVD according to claim 1, which is a VHH domain, a humanized VHH domain, or a camelized VH domain. ### Claim 10 (depends on 3) The fusion polypeptide according to claim 3, wherein the heavy chain ISVDs are linked directly or via a suitable linker.