NZ747752B2 - Anti-factor ix padua antibodies - Google Patents

Anti-factor ix padua antibodies

Info

Publication number
NZ747752B2
NZ747752B2 NZ747752A NZ74775217A NZ747752B2 NZ 747752 B2 NZ747752 B2 NZ 747752B2 NZ 747752 A NZ747752 A NZ 747752A NZ 74775217 A NZ74775217 A NZ 74775217A NZ 747752 B2 NZ747752 B2 NZ 747752B2
Authority
NZ
New Zealand
Prior art keywords
antibody
antigen
binding fragment
factor
polypeptide
Prior art date
Application number
NZ747752A
Other versions
NZ747752A (en
Inventor
Andrea Engelmaier
Robert Pachlinger
Hanspeter Rottensteiner
Dirk Voelkel
Alfred Weber
Original Assignee
Takeda Pharmaceutical Company Limited
Filing date
Publication date
Application filed by Takeda Pharmaceutical Company Limited filed Critical Takeda Pharmaceutical Company Limited
Priority claimed from PCT/US2017/032808 external-priority patent/WO2017200981A1/en
Publication of NZ747752A publication Critical patent/NZ747752A/en
Publication of NZ747752B2 publication Critical patent/NZ747752B2/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/005—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies constructed by phage libraries
    • 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
    • C07K16/36—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against blood coagulation factors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • 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
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • 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
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • 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
    • C07K2317/55—Fab or Fab'
    • 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
    • C07K2319/00—Fusion polypeptide
    • C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
    • C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
    • C07K2319/43—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation containing a FLAG-tag
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/914—Hydrolases (3)
    • G01N2333/948—Hydrolases (3) acting on peptide bonds (3.4)
    • G01N2333/95—Proteinases, i.e. endopeptidases (3.4.21-3.4.99)
    • G01N2333/964—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue
    • G01N2333/96425—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals
    • G01N2333/96427—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general
    • G01N2333/9643—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general with EC number
    • G01N2333/96433—Serine endopeptidases (3.4.21)
    • G01N2333/96441—Serine endopeptidases (3.4.21) with definite EC number
    • G01N2333/9645—Factor IX (3.4.21.22)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/86—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood coagulating time or factors, or their receptors

Abstract

Provided herein are anti-Factor IX Padua binding constructs, e.g., antibodies and antigen-binding fragments thereof. Related polypeptides, conjugates and kits are also provided. The inventions may be used in methods of detecting Factor IX Padua in a sample.

Claims (50)

WHAT IS CLAIMED IS:
1. An dy or antigen-binding fragment thereof that binds a Factor IX Padua and does not bind to a wild-type (WT) Factor IX, comprising the amino acid sequences of: SSYAIS (SEQ ID NO: 6), GIVPAFGTANYAQKFQG (SEQ ID NO: 7), SWGVISFAY (SEQ ID NO: 8), RASQDISSYLN (SEQ ID NO: 9), AASNLQS (SEQ ID NO: 10), and MQYDSLPFTF (SEQ ID NO: 11).
2. The antibody or antigen-binding fragment of claim 1, which binds a Factor IX Padua comprising the amino acid sequence of SEQ ID NO: 1.
3. The antibody or antigen-binding fragment of claim 2, which binds an epitope of SEQ ID NO: 1, wherein the epitope is a linear epitope within the amino acid sequence DRATCLLSTKFT (SEQ ID NO: 3).
4. The antibody or antigen-binding nt of claim 2, which binds to an epitope of SEQ ID NO: 1, n the epitope is a conformational epitope of the folded structure of the amino acid sequence LVDRATCLLSTKFTIYNNMFCAGFH (SEQ ID NO: 5).
5. The antibody or antigen-binding fragment of claim 4, wherein the folded structure comprises a disulfide bridge.
6. The antibody or antigen-binding fragment of any one of claims 1 to 5, which does not bind a wild-type (WT) Factor IX comprising the amino acid ce SEQ ID NO: 2.
7. The antibody or n-binding fragment of any one of claims 1 to 6, which does not bind to at least one of an amino acid sequence of DRATCLRSTKFT (SEQ ID NO: 14) or an amino acid sequence of LVDRATCLRSTKFTIYNNMFCAGFH (SEQ ID NO: 15).
8. The antibody or antigen-binding fragment of any one of claims 1 to 7, n the antibody or n-binding fragment binds to the Factor IX Padua with a KD of about 100 nM or less.
9. The antibody or antigen-binding fragment of claim 8, wherein the antibody or antigen-binding fragment binds to the Factor IX Padua with a KD within a range of about 25 to about 75 nM.
10. The antibody or antigen-binding fragment of claim 9, wherein the antibody or antigen-binding fragment binds to the Factor IX Padua with a KD within a range of about 50 nM to about 60 nM.
11. The dy or antigen-binding fragment of any one of claims 1 to 10, wherein the antibody or antigen-binding fragment binds to the Factor IX Padua and does not bind to a WT Factor IX in a sample comprising human plasma.
12. The dy or antigen-binding fragment of claim 11, wherein the sample comprises at least or about 5%, at least or about 10%, or at least or about 20% human plasma and the sample comprises at least or about 5 µg/mL WT Factor
13. The antibody or antigen-binding fragment of any one of claims 1 to 12, wherein the dy or antigen-binding fragment does not bind to at least one of a Factor II polypeptide or a Factor X polypeptide.
14. The antibody or antigen-binding fragment of any one of claims 1 to 13, which is a Fab or Fab2' antibody fragment.
15. The antibody or antigen-binding fragment of any one of claims 1 to 14, which is monospecific.
16. The antibody or n-binding fragment of any one of claims 1 to 15, which is fully human.
17. The antibody or antigen-binding nt of any one of claims 1 to 16, which is bivalent.
18. The antibody or antigen-binding fragment of any one of claims 1 to 17, comprising dimerized Fab fragments or dimerized Fab mini antibody.
19. The antibody or antigen-binding fragment of any one of claims 1 to 18, which is a dimerized Fab fragment via a linker.
20. The antibody or antigen-binding fragment of any one of claims 1 to 19, comprising (i) the amino acid sequence of SEQ ID NOs: 24 and 25; or (ii) the amino acid sequence of SEQ ID NOs: 26 and 27.
21. A polypeptide sing an amino acid sequence comprising each of SEQ ID NOs: 6-11.
22, The polypeptide of claim 21, wherein the polypeptide specifically recognizes Factor IX Padua t cross-reactivity to WT Factor IX.
23. The polypeptide of claim 21 or 22, wherein one or more amino acids are present between each of SEQ ID NOs: 6-11.
24. The polypeptide of any one of claims 21 to 23, wherein the polypeptide further ses a FLAG tag comprising DYKDDDDK (SEQ ID NO: 12) and/or a hexa-His tag comprising HHHHHH (SEQ ID NO: 13).
25. The polypeptide of claim 24, wherein the FLAG tag and/or the hexa-His tag are located at the C-terminal end of the polypeptide.
26. A conjugate comprising the antibody or antigen-binding nt of any one of claims 1 to 20 or the polypeptide of any one of claims 21 to 25, conjugated to a heterologous moiety.
27. The ate of claim 26, n the heterologous moiety is selected from the group consisting of: a polymer, a carbohydrate, a lipid, a c acid, an oligonucleotide, an amino acid, peptide, polypeptide, protein, and a detecting agent.
28. The conjugate of claim 26 or claim 27, wherein the antibody or antigen-binding fragment or polypeptide is conjugated to agarose, cellulose, dextran, polyacrylamide, latex or controlled pore glass.
29. The conjugate of any one of claims 26 to 28, n the antibody or antigenbinding fragment or polypeptide is conjugated to a fluorophore, chromophore, radioisotope, enzymatic label, or biotin.
30. The conjugate of any one of claims 26 to 29, comprising a homodimer of the polypeptide of any one of claims 21 to 25.
31. The conjugate of claim 30, wherein the polypeptides of the dimer are linked via a helix-turn-helix structure.
32. A nucleic acid comprising a nucleotide sequence ng the antibody or antigen- binding fragment of any one of claims 1 to 20, the polypeptide of any one of claims 21 to 25, the ate of any one of claims 26 to 31, or a fragment thereof.
33. A vector comprising the nucleic acid of claim 32.
34. An isolated host cell sing the nucleic acid of claim 32 or the vector of claim 33.
35. A kit comprising (i) the dy or antigen-binding fragment of any one of claims 1 to 20, the polypeptide of any one of claims 21 to 25, the ate of any one of claims 26 to 31, the c acid of claim 32, the vector of claim 33, the host cell of claim 34, or combinations thereof.
36. The kit of claim 35, further comprising a solid support.
37. The kit of claim 36, wherein the antibody, antigen-binding fragment, polypeptide or conjugate is pre-coated on the solid support.
38. The kit of claim 36 or claim 37, wherein the solid support is a polymer bead, a microtiter plate, a membrane, or a filter.
39. The kit of any one of claims 36 to 38, comprising a solid support pre-coated with a solution comprising about 100 ng or more, about 150 ng or more, about 200 ng or more, about 500 ng or more of the antigen binding nt.
40. A composition comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 20 d with a biological sample obtained from a human comprising human plasma, or a diluted fraction thereof, and/or human , or cells thereof.
41. A composition comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 20 admixed with a biological sample obtained from a human comprising human plasma proteins, wherein at least one of the human plasma proteins is selected from the group consisting of Factor IX, or a variant thereof, Factor II, and Factor X.
42. The composition of claim 40 or claim 41, wherein the composition comprises a detecting agent.
43. Use of the antibody or antigen-binding fragment of any one of claims 1 to 20, the polypeptide of any one of claims 21 to 25, the conjugate of any one of claims 26 to 31, the c acid of claim 32, the vector of claim 33, the host cell of claim 34, and/or the kit of any one of claims 35 to 39 for detecting Factor IX Padua in a sample.
44. A method of detecting Factor IX Padua in a sample obtained from a subject, comprising (i) ting the sample with the antibody or antigen-binding nt of any one of claims 1 to 20, the polypeptide of any one of claims 21 to 25, or the conjugate of any one of claims 26 to 31 to form a complex comprising the Factor IX Padua and the antibody, antigen-binding nt, polypeptide or ate, and (ii) detecting the complex in the sample.
45. The method of claim 44, wherein the antibody or antigen-binding fragment or ptide is conjugated to a detecting agent and/or a solid support or wherein the conjugate comprises a detecting agent.
46. The method of claim 45, comprising contacting the sample with a secondary antibody comprising a detecting agent, wherein the secondary antibody binds to the antibody or antigen-binding fragment or polypeptide or conjugate.
47. The method of claim 45 or claim 34, wherein ing the complex comprises detecting a signal of the detecting agent.
48. The method of claim 47, wherein the signal is an enzymatic activity, binding activity and/or chromogenic activity.
49. The method of any one of claims 44 to 48, wherein the sample is a blood sample, a serum sample, or a plasma .
50. The method of any one of claims 44 to 49, wherein the subject has been treated with a vector comprising a nucleotide sequence encoding Factor IX Padua. mm?mmm zoqua?? 23.5 ngm. ..H. H m m __......H a; FiCHQFLL 1W30 , (CPL >). .3.) I1h1.«J14 ELIEOOYDD... gm .FIL...D N mod MB;... zoEwoa- mmgm m. ngmm zoEwE 226% 0.2% mw?mm HHEHEH._.-.mmH: KVNHE?1:: 93-3wmniu? 7».W1D> m _ 5+0. DHMHEHHN..H 4 3%..er $on $1.me ,awim ..HQH..H..m..m.HHH.H ....H..H9HH..H§mmeHmHH mzwzwmmqmaq $2154. H w H .H...
NZ747752A 2017-05-16 Anti-factor ix padua antibodies NZ747752B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662337118P 2016-05-16 2016-05-16
US201662340834P 2016-05-24 2016-05-24
PCT/US2017/032808 WO2017200981A1 (en) 2016-05-16 2017-05-16 Anti-factor ix padua antibodies

Publications (2)

Publication Number Publication Date
NZ747752A NZ747752A (en) 2025-05-30
NZ747752B2 true NZ747752B2 (en) 2025-09-02

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