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NZ763852B2 - Improved immunoglobulin variable domains - Google Patents
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NZ763852B2 - Improved immunoglobulin variable domains - Google Patents

Improved immunoglobulin variable domains Download PDF

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Publication number
NZ763852B2
NZ763852B2 NZ763852A NZ76385215A NZ763852B2 NZ 763852 B2 NZ763852 B2 NZ 763852B2 NZ 763852 A NZ763852 A NZ 763852A NZ 76385215 A NZ76385215 A NZ 76385215A NZ 763852 B2 NZ763852 B2 NZ 763852B2
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NZ
New Zealand
Prior art keywords
amino acid
acid residue
isvd
polypeptide according
seq
Prior art date
Application number
NZ763852A
Other versions
NZ763852A (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 NZ763852A publication Critical patent/NZ763852A/en
Publication of NZ763852B2 publication Critical patent/NZ763852B2/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

Polypeptide that comprises at least two immunoglobulin single variable domains (ISVDs), either linked directly or via a suitable linker, in which essentially each ISVD is an ISVD in which the amino acid residue at position 11 is one of L, V and K; 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 one of T, V and 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 one of S, K and Q; such that (i) the amino acid residue at position 112 is one of K and 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 110 is one of K and Q, wherein the amino acid residues/positions are indicated with the numbering according to Kabat.

Claims (13)

1. Polypeptide that comprises at least two immunoglobulin single variable domains (ISVDs), either linked directly or via a suitable linker, in which each ISVD is an ISVD in which: - the amino acid residue at position 11 is one of L, V and K; 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 one of T, V and 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 one of S, K and Q; such that (i) the amino acid residue at position 112 is one of K and 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 110 is one of K and Q, wherein the amino acid residues/positions are indicated with the numbering according to Kabat.
2. Polypeptide according to claim 1, that comprises at least two ISVDs, either linked directly or via a suitable linker, in which each ISVD is an 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 one of S, K and Q.
3. Polypeptide according to any of claims 1 or 2, in which each ISVD is an ISVD in which: - the amino acid residue at position 11 is V and the amino acid residue at position 89 is L; - the amino acid residue at position 89 is T; - the amino acid residue at position 89 is L and the amino acid residue at position 110 is one of K and Q; or - the amino acid residue at position 112 is one of K and Q.
4. Polypeptide according to claim 3, in which the amino acid residue at position 11 is V.
5. Polypeptide that comprises at least two ISVDs, either linked directly or via a suitable linker, in which each ISVD is an ISVD in which the amino acid residue at position 11 is V and the amino acid residue at position 89 is L, wherein the amino acid residues/positions are indicated with the numbering according to Kabat.
6. Polypeptide according to any of claims 1 to 5, that comprises at its C-terminal end 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).
7. Polypeptide according to any of claims 1 to 6 in which each ISVD is a VHH domain, a humanized VHH domain or a camelized VH domain.
8. Polypeptide according to any of claims 1 to 7, that comprises an ISVD which is directed against Kv1.3, IL-23, OX40L, IgE, CXCR4, HER3, TNF, c-Met, RANKL, CXCR7 or A-beta.
9. Polypeptide according to claim 8, that comprises an ISVD 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).
10. Polypeptide according to claim 9, that comprises one of SEQ ID NOs: 338-339 and 346-
11. Polypeptide according to claim 8, that comprises an ISVD 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).
12. Polypeptide according to claim 11, that comprises one of SEQ ID NOs: 320-321 and 328-
13. Polypeptide according to any of claims 1 to 12, that has a half-life (expressed as t
NZ763852A 2015-05-13 Improved immunoglobulin variable domains NZ763852B2 (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
NZ763852A NZ763852A (en) 2024-08-30
NZ763852B2 true NZ763852B2 (en) 2024-12-03

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