Deprecated: The each() function is deprecated. This message will be suppressed on further calls in /home/zhenxiangba/zhenxiangba.com/public_html/phproxy-improved-master/index.php on line 456
NZ778208B2 - Humanized or chimeric CD3 antibodies - Google Patents
[go: Go Back, main page]

NZ778208B2 - Humanized or chimeric CD3 antibodies - Google Patents

Humanized or chimeric CD3 antibodies

Info

Publication number
NZ778208B2
NZ778208B2 NZ778208A NZ77820816A NZ778208B2 NZ 778208 B2 NZ778208 B2 NZ 778208B2 NZ 778208 A NZ778208 A NZ 778208A NZ 77820816 A NZ77820816 A NZ 77820816A NZ 778208 B2 NZ778208 B2 NZ 778208B2
Authority
NZ
New Zealand
Prior art keywords
heavy chain
antibody
region
antibody according
seq
Prior art date
Application number
NZ778208A
Other versions
NZ778208A (en
Inventor
Isil Altintas
Patrick Engelberts
Paul Parren
Rik Rademaker
Janine Schuurman
Original Assignee
Genmab A/S
Filing date
Publication date
Priority claimed from PCT/EP2016/050296 external-priority patent/WO2016110576A1/en
Application filed by Genmab A/S filed Critical Genmab A/S
Priority claimed from NZ739028A external-priority patent/NZ739028A/en
Publication of NZ778208A publication Critical patent/NZ778208A/en
Publication of NZ778208B2 publication Critical patent/NZ778208B2/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • 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
    • C07K16/2803—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 immunoglobulin superfamily
    • C07K16/2809—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 immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
    • 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
    • C07K16/4208—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an idiotypic determinant on Ig
    • C07K16/4216—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an idiotypic determinant on Ig against anti-viral Ig
    • 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
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/526—CH3 domain
    • 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
    • C07K2317/50—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
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • 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

Abstract

The present invention relates to humanized or chimeric antibodies binding CD3. It furthermore relates to bispecific antibodies, compositions, pharmaceutical compositions, use of said antibodies in the treatment of a disease, and method of treatment.

Claims (29)

Claims
1. A humanized or chimeric antibody g to human CD3, wherein said antibody comprises a binding region sing a heavy chain variable (VH) region and a light chain variable (VL) region, wherein said VH region comprises CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NO: 1, 2 and 220 [G105P], and wherein said VL region comprises CDR1, CDR2, and CDR3 regions having the CDR sequences as set forth in SEQ ID NO:6, GTN and 7.
2. The antibody according to claim 1, wherein said VH region has a VH sequence as set forth in SEQ ID NO: 221 [G105P], or a VH ce having at least 90%, at least 95%, at least 97% or at least 99% amino acid sequence identity to the sequence as set forth in SEQ ID NO: 221.
3. The antibody according to claim 1 or 2, wherein said VH region has a VH sequence as set forth in SEQ ID NO: 221 [G105P].
4. The antibody according to any one of the preceding claims, wherein said binding region comprises a variable light chain (VL) region, wherein said VL region is ed from the group ting of; a) a VL sequence as set forth in SEQ ID NO:8; b) a VL sequence as set forth in SEQ ID NO:10 or c) a VL sequence having at least 90%, at least 95%, at least 97% or at least 99% amino acid sequence identity to any one of the sequences as set forth in a) to b).
5. The antibody according to any one of the preceding claims, wherein said VH region has a VH sequence as set forth in SEQ ID NO: 221 [G105P] and said VL region has a VL sequence as set forth in SEQ ID NO: 8.
6. The dy ing to any one of claims 1 to 4, wherein said VH region has a VH sequence as set forth in SEQ ID NO: 221 [G105P] and said VL region has a VL sequence as set forth in SEQ ID NO: 10.
7. The dy according to any one of the preceding claims, wherein human CD3 is human CD3 epsilon as specified in SEQ ID NO: 399.
8. The antibody according to any one of the preceding claims, wherein the antibody is a humanized antibody; 21345876_1 (GHMatters) P43747NZ02 a full-length dy; of an isotype selected from the group consisting of IgG1, IgG2, IgG3, and IgG4; and/or antibody is monovalent, bivalent or multivalent.
9. The antibody according to any one of the preceding claims, wherein said antibody comprises: an Fc region sing a first and a second immunoglobulin heavy chain; and/or a first and a second immunoglobulin heavy chain, wherein in at least one of said first and second immunoglobulin heavy chains one or more amino acids in the positions corresponding to positions L234, L235, D265, N297, and P331 in a human IgG1 heavy chain according to EU numbering, are not L, L, D, N, and P, respectively.
10. The antibody according to claim 9, wherein in at least one of said first and second: immunoglobulin heavy chains the amino acid in the position corresponding to position D265 in a human IgG1 heavy chain, is not D; heavy chains the amino acid in the position corresponding to position N297 in a human IgG1 heavy chain, is not N; heavy chains the amino acids in the positions corresponding to positions L234 and L235 in a human IgG1 heavy chain, are not L and L, respectively; heavy chains the amino acids in the positions corresponding to ons L234 and L235 in a human IgG1 heavy chain, are F and E; or A and A, respectively; heavy chains the amino acids in the positions corresponding to positions L234 and L235 in a human IgG1 heavy chain, are F and E, respectively; heavy chains the amino acids in the positions corresponding to positions L234 and L235 in a human IgG1 heavy chain, are A and A, respectively; heavy chains the amino acids in the positions corresponding to positions L234, L235, and D265 in a human IgG1 heavy chain, are not L, L, and D, respectively; heavy chains the amino acids in the ons corresponding to positions L234, L235, and D265 in a human IgG1 heavy chain, are F, E, and A; or A, A, and A, tively; heavy chains the amino acids in the positions corresponding to positions L234, L235, and D265 in a human IgG1 heavy chain, are F, E, and A, respectively; heavy chains the amino acids in the positions corresponding to positions L234, L235, and D265 in a human IgG1 heavy chain, are A, A, and A, respectively; and/or heavy chains the amino acids in the ons ponding to positions L234, L235, D265, N297, and P331 in a human IgG1 heavy chain, are F, E, A, Q, and S, respectively. 21345876_1 (GHMatters) P43747NZ02
11. A bispecific antibody comprising a first binding region of an antibody ing to any one of the preceding claims, and a second binding region which binds a ent target than said first antigen binding region.
12. The bispecific antibody according to claim 11 wherein said antibody comprises a first and a second heavy chain, and wherein each of said first and second heavy chain comprises at least a hinge region, a CH2 and CH3 region, n in said first heavy chain at least one of the amino acids in the positions corresponding to a positions selected from the group consisting of T366, L368, K370, D399, F405, Y407, and K409 in a human IgG1 heavy chain has been substituted, and in said second heavy chain at least one of the amino acids in the positions corresponding to a position selected from the group consisting of T366, L368, K370, D399, F405, Y407, and K409 in a human IgG1 heavy chain has been substituted, and wherein said first and said second heavy chains are not substituted in the same positions.
13. The ific antibody ing to claim 12, wherein the amino acid in the position ponding to F405 in a human IgG1 heavy chain is L in said first heavy chain, and the amino acid in the position corresponding to K409 in a human IgG1 heavy chain is R in said second heavy chain, or vice versa.
14. A method of sing the binding affinity of an antibody binding to human CD3 compared to a reference dy comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein said VH region comprises the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 1, 2, 3, which method comprises introducing a mutation in the VH CDR3, wherein the mutation is G105P, wherein the position is numbered according to the reference ce of the SEQ ID NO: 4; and wherein said VL region comprises CDR1, CDR2, and CDR3 regions having the CDR sequences as set forth in SEQ ID NO:6, GTN and 7, respectively.
15. The antibody or method according to any one of the preceding claims, wherein the antibody has a binding affinity to human CD3 epsilon peptide with SEQ ID NO: 402 corresponding to a KD value from 1.0x10-7 to 9.9x10-7 M as determined by Bio-Layer Interferometry.
16. The antibody or method according to claim 15, wherein the human CD3 epsilon is expressed on a T cell or is in isolated form, e.g. an ed human CD3 epsilonpeptide. 21633893_1 (GHMatters) P43747NZ02
17. A nucleic acid construct encoding of the VH and VL regions as defined in any one of claims 1-10, or a set of nucleic acid constructs sing: (i) a first nucleic aid construct ng the VH region as defined in any one of claims 1 to 10, and (ii) a second nucleic aid construct encoding the VL region as defined in any one of claims 1 to 10.
18. An expression vector comprising (i) a nucleic acid sequence encoding a heavy chain sequence of a humanized or chimeric antibody according to any one of claims 1 to 0; and (ii) a nucleic acid sequence encoding a light chain sequence of a humanized or chimeric antibody according to any one of claims 1 to 10; or a set of expression s comprising (i) a first expression vector comprising a nucleic acid sequence ng a heavy chain sequence of a humanized or chimeric dy according to any one of claims 1 to 10; (ii) a second expression vector comprising a nucleic acid sequence encoding a light chain sequence of a humanized or chimeric antibody according to any one of claims 1 to 10.
19. An isolated and/or non-human host cell comprising an expression vector or set of expression s of claim 18.
20. The host cell according to claim 19, wherein said host cell is a recombinant eukaryotic, recombinant prokaryotic, or inant microbial host cell.
21. A composition comprising an antibody according to any one of claims 1 to 10 or a bispecific antibody according to any one of claims 11 to 13.
22. A pharmaceutical composition comprising the antibody according to any one of claims 1 to 10, or the bispecific antibody according to any one of claims 11-13 and a pharmaceutical acceptable r.
23. The antibody according to any one of claims 1 to 13, the composition according to claim 21, or the pharmaceutical composition according to claim 22 for use as a 93_1 (GHMatters) P43747NZ02 medicament; for use as a medicament in treating cancer, an infectious disease, or autoimmune diseases; and/or for use in treating a disease.
24. Use of the antibody according to any one of claims 1 to 10, or the bispecific antibody ing to any one of claims 11-13, in the preparation of a ment for treating a disease, or for treating cancer, an ious disease, or an autoimmune disease in a subject.
25. Use of the antibody according to claim 24, wherein the subject is determined by detecting the presence or absence of a complex formed between the antibody according to any one of claims 1 to 10, or the bispecific antibody according to any one of claims 11-13, and CD3, optionally wherein said antibody is labeled with a detectable agent.
26. A method for producing an antibody according to any one of claims 1 to 13, comprising the steps of a) ing a host cell according to claim 20; and b) ing said antibody from the culture media.
27. A stic composition comprising an antibody according to any one of claims 1 to 10 or a bispecific antibody according to any one of claims 11 to 13.
28. A method for detecting the presence of CD3 antigen, or a cell expressing CD3, in a sample comprising the steps of; a) contacting the sample with an antibody according to any one of claims 1 to 10 or a bispecific antibody ing to any one of claims 11 to 13, under conditions that allow for formation of a complex between said antibody or bispecific antibody and CD3; and b) analyzing whether a complex has been .
29. A kit for ing the presence of CD3 antigen, or a cell expressing CD3, in a sample comprising i) an antibody according to any one of claims 1 to 10 or a bispecific antibody according to any one of claims 11 to 13; and ii) instructions for use of said kit. 21633893_1 (GHMatters) P43747NZ02 1/ 13
NZ778208A 2016-07-14 Humanized or chimeric CD3 antibodies NZ778208B2 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
DKPA201500413 2015-07-15
DKPA201500414 2015-07-15
DKPA201500416 2015-07-16
PCT/EP2016/050296 WO2016110576A1 (en) 2015-01-08 2016-01-08 Bispecific antibodies against cd3 and cd20
NZ739028A NZ739028A (en) 2015-07-15 2016-07-14 Humanized or chimeric cd3 antibodies

Publications (2)

Publication Number Publication Date
NZ778208A NZ778208A (en) 2025-05-02
NZ778208B2 true NZ778208B2 (en) 2025-08-05

Family

ID=

Similar Documents

Publication Publication Date Title
FI3322727T3 (en) Humanized or chimeric CD3 antibodies
JP2018526981A5 (en)
JP2020048564A5 (en)
US9409979B2 (en) Acceptor framework for CDR grafting
JP2016529882A5 (en)
JP2020508655A5 (en)
HRP20200382T1 (en) Humanized or chimeric cd3 antibodies
JP2017505121A5 (en)
EP3684802A1 (en) Novel stable antibody variable domain framework combinations
HRP20131215T1 (en) Antagonistic human light-specific human monoclonal antibodies
RU2019121086A (en) Immunotherapy using antibodies that bind programmed cell death protein ligand 1 (PD-L1)
KR102058381B1 (en) Humanized antibody against human L1CAM and method for preparing the antibody
HRP20250221T1 (en) ANTI-PAR-2 ANTIBODIES AND METHODS OF USING THEM
RU2019135404A (en) ANTIBODIES FOR THE TREATMENT OF HEPATITIS B INFECTION AND RELATED DISEASES
TW202200620A (en) Anti-flt3 antibodies and compositions
JP2024516098A5 (en)
CN111886023A (en) Antibodies to TIM-3 and uses thereof
JP2025508317A5 (en)
IL277899B2 (en) Methods and compositions for treating yellow fever
TW202130365A (en) Multi-specific antibody with binding specificity for human il-13 and il-17
CN113549152B (en) A kind of anti-BASIGIN humanized antibody and its application
NZ778208B2 (en) Humanized or chimeric CD3 antibodies
NZ778205B2 (en) Humanized or chimeric CD3 antibodies
WO2014124677A1 (en) Acceptor framework for cdr grafting
CN119285769A (en) Multispecific antibodies and their medical uses