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NZ726448B2 - Improved immunoglobulin variable domains - Google Patents

Improved immunoglobulin variable domains

Info

Publication number
NZ726448B2
NZ726448B2 NZ726448A NZ72644815A NZ726448B2 NZ 726448 B2 NZ726448 B2 NZ 726448B2 NZ 726448 A NZ726448 A NZ 726448A NZ 72644815 A NZ72644815 A NZ 72644815A NZ 726448 B2 NZ726448 B2 NZ 726448B2
Authority
NZ
New Zealand
Prior art keywords
amino acid
heavy
seq
acid residue
chain
Prior art date
Application number
NZ726448A
Other versions
NZ726448A (en
Inventor
Carlo Boutton
Marie Ange Buyse
Original Assignee
Ablynx Nv
Filing date
Publication date
Application filed by Ablynx Nv filed Critical Ablynx Nv
Priority to NZ763848A priority Critical patent/NZ763848B2/en
Priority to NZ763845A priority patent/NZ763845B2/en
Priority to NZ763852A priority patent/NZ763852B2/en
Priority to NZ743471A priority patent/NZ743471B2/en
Priority to NZ763850A priority patent/NZ763850B2/en
Priority claimed from PCT/EP2015/060643 external-priority patent/WO2015173325A2/en
Publication of NZ726448A publication Critical patent/NZ726448A/en
Publication of NZ726448B2 publication Critical patent/NZ726448B2/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241—Tumor Necrosis Factors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/244—Interleukins [IL]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2875—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
    • C07K16/4283—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig
    • C07K16/4291—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig against IgE
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/22—Immunoglobulins specific features characterized by taxonomic origin from camelids, e.g. camel, llama or dromedary
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/35—Valency
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/567—Framework region [FR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/31—Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/10—Libraries containing peptides or polypeptides, or derivatives thereof

Abstract

Heavy-chain immunoglobulin single variable domain (ISVD), in which the amino acid residue at position 11 is V and the amino acid residue at position 110 is one of K or Q, (the amino acid positions are indicated with the numbering according to Kabat); preferably, said heavy-chain ISVD contains a C-terminal extension (X)n, in which n is 1 to 10; more preferably, n is 1 to 5, such as 1, 2, 3, 4 or 5; and each X is an amino acid residue that is independently chosen.

Claims (25)

C L A I M S
1. Heavy-chain immunoglobulin single variable domain (ISVD), in which the amino acid residue at position 11 is V and the amino acid residue at position 110 is one of K or Q, wherein the amino acid positions are indicated with the numbering according to Kabat.
2. The heavy-chain ISVD according to claim 1, in which said heavy-chain ISVD contains a C-terminal extension (X) , in which n is 1 to 10; and each X is an amino acid residue that is independently chosen.
3. The heavy-chain ISVD according to claim 2, in which n is 1 to 5, such as 1, 2, 3, 4 or 5.
4. The heavy-chain ISVD according to either of claims 2 or 3, in which X is a naturally occurring amino acid residue that is independently chosen.
5. The heavy-chain ISVD according to any one of claims 2 to 4, in which X is independently chosen from the group consisting of alanine (A), glycine (G), valine (V), leucine (L) or isoleucine (I).
6. The heavy-chain ISVD according to claim 1, in which: - the amino acid residue at position 11 is V; and - the amino acid residue at position 14 is one of A or P; and - the amino acid residue at position 41 is one of A or P; and - the amino acid residue at position 89 is one of T, V or L; and - the amino acid residue at position 108 is one of Q or L; and - the amino acid residue at position 110 is one of K or Q; and - the amino acid residue at position 112 is one of S, K or Q; wherein the amino acid positions are indicated with the numbering according to Kabat.
7. The heavy-chain ISVD according to any one of claims 1 to 6, which is a VHH domain, humanized VHH domain or camelized VH domain.
8. The heavy-chain ISVD according to claim 6 or claim 7, in which said heavy- chain ISVD contains a C-terminal extension (X) , in which n is 1 to 10; and each X is an amino acid residue that is independently chosen.
9. The heavy-chain ISVD according to claim 8, in which n is 1 to 5, such as 1, 2, 3, 4 or 5.
10. The heavy-chain ISVD according to any of claims 8 or 9, in which X is a naturally occurring amino acid residue that is independently chosen.
11. The heavy-chain ISVD according to any one of claims 8 to 10, in which X is independently chosen from the group consisting of alanine (A), glycine (G), valine (V), leucine (L) or isoleucine (I).
12. The heavy-chain ISVD according to any one of claims 1 to 11, which is directed against Kv1.3, IL-23, OX40L, IgE, CXCR4, HER3, TNF, c-Met, RANKL, CXCR7 or A-beta.
13. The heavy-chain ISVD according to claim 12, which can specifically bind to TNF, and in which: - CDR1 is the amino acid sequence TADMG (SEQ ID NO:335); - CDR2 is the amino acid sequence RISGIDGTTYYDEPVKG (SEQ ID NO:336); - CDR3 is the amino acid sequence PRYADQWSAYDY (SEQ ID NO:337).
14. The heavy-chain ISVD according to claim 13, that comprises or consists of one of SEQ ID NOs: 346-349.
15. The heavy-chain ISVD according to claim 12, which can specifically bind to TNF, and in which: - CDR1 is the amino acid sequence DYWMY (SEQ ID NO:317); - CDR2 is the amino acid sequence EINTNGLITKYPDSVKG (SEQ ID NO:318); - CDR3 is the amino acid sequence SPSGFN (SEQ ID NO:319).
16. The heavy-chain ISVD according to claim 15, that comprises or consists of one of SEQ ID NOs: 329-331.
17. The heavy-chain ISVD according to any one of the preceding claims, which can specifically bind to human serum albumin.
18. The heavy-chain ISVD according to claim 17, in which: - CDR1 is the amino acid sequence SFGMS (SEQ ID NO:41); - CDR2 is the amino acid sequence SISGSGSDTLYADSVKG (SEQ ID NO:42); - CDR3 is the amino acid sequence GGSLSR (SEQ ID NO:43).
19. The heavy-chain ISVD according to either of claims 17 or 18, in which the amino acid residue at position 11 is V and the amino acid residue at position 110 is K or Q, which can specifically bind to human serum albumin, and which heavy-chain ISVD has at least 80% sequence identity with at least one of Alb-1 (SEQ ID NO: 52 of ), Alb-8 (SEQ ID NO: 46) and/or Alb-23 (SEQ ID NO:61).
20. The heavy-chain ISVD according to any one of claims 17 to 19, that comprises or consists of one of SEQ ID NOs: 123-136, 500-502, and 509-511.
21. Library of heavy-chain ISVDs according to any one of claims 1 to 11.
22. Library of nucleic acid residues encoding a heavy-chain ISVD according to any one of claims 1 to 11.
23. Library according to claim 22, which is an expression library.
24. Library according to any one of claims 21 to 23, which is a synthetic library.
25. Library according to any one of claims 21 to 23, which contains at least 100 different sequences, such as at least 1000 different sequences, more than 10 different 6 8 10 sequences, more than 10 different sequences, such as 10 to 10 or more different sequences.
NZ726448A 2015-05-13 Improved immunoglobulin variable domains NZ726448B2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
NZ763848A NZ763848B2 (en) 2015-05-13 Improved immunoglobulin variable domains
NZ763845A NZ763845B2 (en) 2015-05-13 Improved immunoglobulin variable domains
NZ763852A NZ763852B2 (en) 2015-05-13 Improved immunoglobulin variable domains
NZ743471A NZ743471B2 (en) 2015-05-13 Improved immunoglobulin variable domains
NZ763850A NZ763850B2 (en) 2015-05-13 Improved immunoglobulin variable domains

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201461994552P 2014-05-16 2014-05-16
US201461014015P 2014-06-18 2014-06-18
US201462014015P 2014-06-18 2014-06-18
US201462040167P 2014-08-21 2014-08-21
US201462047560P 2014-09-08 2014-09-08
US201562133600P 2015-03-16 2015-03-16
PCT/EP2015/060643 WO2015173325A2 (en) 2014-05-16 2015-05-13 Improved immunoglobulin variable domains

Publications (2)

Publication Number Publication Date
NZ726448A NZ726448A (en) 2023-02-24
NZ726448B2 true NZ726448B2 (en) 2023-05-25

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