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NZ763845B2 - Improved immunoglobulin variable domains - Google Patents
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NZ763845B2 - Improved immunoglobulin variable domains - Google Patents

Improved immunoglobulin variable domains Download PDF

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Publication number
NZ763845B2
NZ763845B2 NZ763845A NZ76384515A NZ763845B2 NZ 763845 B2 NZ763845 B2 NZ 763845B2 NZ 763845 A NZ763845 A NZ 763845A NZ 76384515 A NZ76384515 A NZ 76384515A NZ 763845 B2 NZ763845 B2 NZ 763845B2
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NZ
New Zealand
Prior art keywords
heavy
amino acid
chain isvd
chain
seq
Prior art date
Application number
NZ763845A
Other versions
NZ763845A (en
Inventor
Carlo Boutton
Marie Ange Buyse
Original Assignee
Ablynx Nv
Filing date
Publication date
Application filed by Ablynx Nv filed Critical Ablynx Nv
Publication of NZ763845A publication Critical patent/NZ763845A/en
Publication of NZ763845B2 publication Critical patent/NZ763845B2/en

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    • 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 [IG], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IG], 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 [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IG], 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 [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IG], 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 [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], 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 [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863—Immunoglobulins [IG], 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 [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2866—Immunoglobulins [IG], 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 [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2875—Immunoglobulins [IG], 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 [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], 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 [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/32—Immunoglobulins [IG], 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 [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/42—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against immunoglobulins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/42—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against immunoglobulins
    • C07K16/4283—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig
    • C07K16/4291—Immunoglobulins [IG], 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
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • 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
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
    • 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

Abstract

Heavy-chain immunoglobulin single variable domain (ISVD), in which the amino acid residue at position 89 is L and the amino acid residue at position 11 is V, wherein the amino acid residues/positions are indicated with the numbering according to Kabat.

Claims (38)

1. Heavy-chain immunoglobulin single variable domain (ISVD), in which the amino acid residue at position 89 is L and the amino acid residue at position 11 is V, wherein the amino acid residues/positions are indicated with the numbering according to Kabat.
2. Heavy-chain ISVD according to claim 1 that (i) contains an amino acid at position 110 that is chosen from T, I or A; and (ii) contains an amino acid at position 112 that is chosen from S or F.
3. Heavy-chain ISVD according to claim 2 that contains a P14A or A14P substitution and/or a Q108L substitution.
4. Heavy-chain ISVD according to any of claims 2 or 3 that (i) contains an amino acid at position 110 that is T; and (ii) contains an amino acid at position 112 that is S.
5. Heavy-chain ISVD according to claim 4 that contains a P14A or A14P substitution and/or a Q108L substitution.
6. Heavy-chain ISVD according to any of claims 4 or 5 that (i) contains an amino acid at position 110 that is T; and (ii) contains an amino acid at position 112 that is chosen from S.
7. Heavy-chain ISVD according to claim 6 that contains a P14A or A14P substitution and/or a Q108L substitution.
8. Heavy-chain ISVD according to any of claims 4 or 5 that contains an amino acid at position 112 that is S.
9. Heavy-chain ISVD according to claim 8 that contains a P14A or A14P substitution and/or a Q108L substitution.
10. Heavy-chain ISVD according to any of claims 1 to 9, in which said heavy-chain ISVD contains a C-terminal extension (X)n , in which n is 1 to 10; and each X is an amino acid residue that is independently chosen.
11. Heavy-chain ISVD according to claim 10, in which n is 1, 2, 3, 4 or 5.
12. Heavy-chain ISVD according to claim 10, in which n is 1 or 2.
13. Heavy-chain ISVD according to claim 10, in which n is 1.
14. Heavy-chain ISVD according to any of claims 10 to 13, in which each X is a naturally occurring amino acid.
15. Heavy-chain ISVD according to any of claims 10 to 13, in which each X is independently chosen from the group consisting of alanine (A), glycine (G), valine (V), leucine (L) or isoleucine (I).
16. Heavy-chain ISVD according to any of claims 1 to 15, in which the C-terminal end of the heavy-chain ISVD is one of: VTVSS (SEQ ID NO:76), VTVSS(X)n (SEQ ID NO:77), in which n is 1 to 10; and each X is an amino acid residue that is independently chosen.
17. Heavy-chain ISVD according to claim 16, in which n is 1, 2, 3, 4 or 5.
18. Heavy-chain ISVD according to claim 16, in which n is 1 or 2.
19. Heavy-chain ISVD according to claim 16, in which n is 1.
20. Heavy-chain ISVD according to any of claims 16 to 19, in which each X is a naturally occurring amino acid.
21. Heavy-chain ISVD according to any of claims 16 to 19, in which each X is independently chosen from the group consisting of alanine (A), glycine (G), valine (V), leucine (L) or isoleucine (I).
22. Heavy-chain ISVD, in which: - the amino acid residue at position 11 is V; and - the amino acid residue at position 14 is one of A and P; and - the amino acid residue at position 41 is one of A and P; and - the amino acid residue at position 89 is L; and - the amino acid residue at position 108 is one of Q and L; and - the amino acid residue at position 110 is one of T, K and Q; and - the amino acid residue at position 112 is S, wherein the amino acid residues/positions are indicated with the numbering according to Kabat.
23. Heavy-chain ISVD according to claim 22, in which the amino acid residue at position 110 is T.
24. Heavy-chain ISVD according to any of claims 22 to 23, in which said heavy-chain ISVD contains a C-terminal extension (X)n, in which n is 1 to 10; and each X is an amino acid residue that is independently chosen.
25. Heavy-chain ISVD according to claim 24, in which n is 1, 2, 3, 4 or 5.
26. Heavy-chain ISVD according to claim 24, in which n is 1 or 2.
27. Heavy-chain ISVD according to claim 24, in which n is 1.
28. Heavy-chain ISVD according to any of claims 24 to 27, in which each X is a naturally occurring amino acid.
29. Heavy-chain ISVD according to any of claims 24 to 27, in which each X is independently chosen from the group consisting of alanine (A), glycine (G), valine (V), leucine (L) or isoleucine (I).
30. Heavy-chain ISVD according to any of claims 1 to 29, which is a VHH domain, humanized VHH domain or camelized VH domain.
31. Heavy-chain ISVD according to any of claims 1 to 30, which is directed against Kv1.3, IL-23, OX40L, IgE, CXCR4, HER3, TNF, c-Met, RANKL, CXCR7 or A-beta.
32. Heavy-chain ISVD according to claim 31, 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).
33. Heavy-chain ISVD according to claim 32, that comprises or consists of one of SEQ ID NOs: 345-347.
34. Heavy-chain ISVD according to claim 31, 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).
35. Heavy-chain ISVD according to claim 34, that comprises or consists of one of SEQ ID NOs: 327-329.
36. Heavy-chain ISVD according to any of claims 1 to 30, which can specifically bind to human serum albumin.
37. Heavy-chain ISVD according to claim 36, which can specifically bind to human serum albumin, in which heavy-chain ISVD: - 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).
38. Heavy-chain ISVD according to any of claims 36 or 37, in which the amino acid residue at position 89 is L and the amino acid residue at position 11 is V, 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 , SEQ ID NO: 767 in the present specification), Alb-8 (SEQ ID NO: 46) and/or Alb-23 (SEQ ID NO:61).
NZ763845A 2015-05-13 Improved immunoglobulin variable domains NZ763845B2 (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201461994552P 2014-05-16 2014-05-16
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
NZ726448A NZ726448B2 (en) 2015-05-13 Improved immunoglobulin variable domains

Publications (2)

Publication Number Publication Date
NZ763845A NZ763845A (en) 2024-08-30
NZ763845B2 true NZ763845B2 (en) 2024-12-03

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