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NZ779076B2 - Combinations of binding moieties that bind egfr, her2 and her3. - Google Patents
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NZ779076B2 - Combinations of binding moieties that bind egfr, her2 and her3. - Google Patents

Combinations of binding moieties that bind egfr, her2 and her3.

Info

Publication number
NZ779076B2
NZ779076B2 NZ779076A NZ77907620A NZ779076B2 NZ 779076 B2 NZ779076 B2 NZ 779076B2 NZ 779076 A NZ779076 A NZ 779076A NZ 77907620 A NZ77907620 A NZ 77907620A NZ 779076 B2 NZ779076 B2 NZ 779076B2
Authority
NZ
New Zealand
Prior art keywords
binds
domain
composition
her3
egfr
Prior art date
Application number
NZ779076A
Other versions
NZ779076A (en
Inventor
Kruif Cornelis Adriaan De
Tristan Louis Jean Gallenne
Cecilia Anna Wilhelmina Geuijen
Mark Throsby
Original Assignee
Merus Nv
Filing date
Publication date
Application filed by Merus Nv filed Critical Merus Nv
Priority claimed from PCT/NL2020/050081 external-priority patent/WO2020167123A1/en
Publication of NZ779076A publication Critical patent/NZ779076A/en
Publication of NZ779076B2 publication Critical patent/NZ779076B2/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
    • 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
    • A61K2039/507—Comprising a combination of two or more separate antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07K16/32—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
    • 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
    • C07K2317/34—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
    • C07K2317/50—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
    • C07K2317/56—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
    • C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
    • 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

Abstract

The invention provides a composition comprising two or more binding moieties wherein each of each of said binding moieties comprises a variable domain that binds to an extracellular part of EGFR; and wherein a first of said binding moieties comprises a variable domain that binds to an extracellular part of HER2 and a second of said binding moieties comprises a variable domain that binds to an extracellular part of HER3. The invention also relates to means and method for producing compositions and for the treatment of subjects with the compositions.

Claims (22)

1. A composition comprising two or more dies or fragments thereof, wherein each of said antibodies or fragments thereof comprises a variable domain that binds to an ellular part of EGFR; and wherein a first of said antibodies or fragments thereof comprises a variable domain that binds to an extracellular part of HER2 and a second of said antibodies or fragments thereof comprises a variable domain that binds to an extracellular part of HER3.
2. The composition of claim 1, n at least one and preferably at least two of the two or more antibodies or fragments thereof is a full length antibody.
3. The composition of claim 1 or claim 2, wherein at least one and preferably at least two of the two or more dies or fragments thereof is an IgG.
4. The composition of claim 2 or claim 3, wherein the CH3-regions of the heavy chains of a first and/or a second antibody are engineered to facilitate heterodimerization of a heavy chain with an EGFR binding variable domain with a heavy chain with an HER2 g le domain and/or an EGFR binding variable domain with a heavy chain with an HER3 binding variable domain.
5. The composition of any one of claims 2 to 4, wherein at least one, and preferably at least two of the two or more antibodies is a bispecific antibody.
6. The composition of any one of claims 2 to 5, wherein the variable domains that bind to an ellular part of EGFR of the first and second antibody comprise the same heavy chain variable region.
7. The composition of any one of claims 2 to 6, wherein the variable domain that binds to an extracellular part of EGFR binds domain I or domain III of EGFR, preferably domain III.
8. The composition of any one of claims 2 to 7, wherein the variable domain that binds to an extracellular part of HER2 binds domain I or domain IV of HER2, preferably domain IV.
9. The composition of any one of claims 2 to 8, wherein the variable domain that binds to an extracellular part of HER3 binds domain III of HER3.
10. The composition of any one of claims 6 to 9, wherein the variable domain that binds to an extracellular part of EGFR binds domain I or domain III of EGFR, preferably domain III; wherein the variable domain that binds to an extracellular part of HER2 binds domain I or domain IV of HER2, preferably domain IV; and wherein the le domain that binds to an extracellular part of HER3 binds domain III of HER3.
11. The composition of any one of claims 6 to 9, wherein the variable domain that binds to an extracellular part of EGFR binds domain III of EGFR; wherein the le domain that binds to an extracellular part of HER2 binds domain I or domain IV of HER2; and n the variable domain that binds to an ellular part of HER3 binds domain III of HER3.
12. The composition of any one of claims 6 to 9, wherein the variable domain that binds to an extracellular part of EGFR binds domain I or domain III of EGFR; wherein the variable domain that binds to an extracellular part of HER2 binds domain IV of HER2; and wherein the variable domain that binds to an extracellular part of HER3 binds domain III of HER3.
13. The composition of any one of claims 6 to 9, wherein the variable domain that binds to an extracellular part of EGFR binds domain III of EGFR; wherein the le domain that binds to an extracellular part of HER2 binds domain IV of HER2; and wherein the variable domain that binds to an extracellular part of HER3 binds domain III of HER3.
14. The composition of any one of claims 9 to 13, wherein the variable domain that binds to an extracellular part of HER3 binds at least to R426 of domain III of HER3.
15. The composition of any one of claims 1 to 14, wherein the binding of the variable domain that binds EGFR to EGFR blocks the g of EGF to EGFR and/or wherein the binding of the variable domain that binds HER3 to HER3 blocks the binding of neuregulin 1 (NRG) to HER3.
16. The composition of any one of claims 1-15, wherein the variable domain that binds to an extracellular part of EGFR comprises a heavy chain variable region comprising a CDR1 sequence NYAMN, a CDR2 sequence WINANTGDPTYAQGFTG and a CDR3 sequence ERFLEWLHFDY or a variant thereof comprising a conservative substitution of 1, 2, or 3 amino acids in the CDRs, and wherein said heavy chain variable region comprises a common light chain.
17. The composition of any one of claims 1-16, wherein the variable domain that binds to an extracellular part of HER2 comprises a heavy chain variable region comprising a CDR1 sequence SYGMH, a CDR2 sequence VISYDGSNKYYADSVKG and a CDR3 sequence DYYRRTARAGFDY or a variant thereof comprising a vative substitution of 1, 2, or 3 amino acids in the CDRs, and wherein said heavy chain le region ses a common light chain.
18. The composition of any one of claims 1-17, wherein the variable domain that binds to an extracellular part of HER3 comprises a heavy chain variable region comprising a CDR1 ce GYYMH, a CDR2 sequence WINPNSGGTNYAQKFQG and a CDR3 sequence DHGSRHFWSYWGFDY or a variant f comprising a vative substitution of 1, 2, or 3 amino acids in the CDRs, and wherein said heavy chain variable region comprises a common light chain.
19. The composition of any one of claims 1-18 - wherein the variable domain that binds to an extracellular part of EGFR comprises a heavy chain variable region comprising a CDR1 sequence NYAMN, a CDR2 sequence WINANTGDPTYAQGFTG and a CDR3 sequence ERFLEWLHFDY or a variant thereof sing a conservative tution of 1, 2, or 3 amino acids in the CDRs, and wherein said heavy chain variable region comprises a common light chain; - wherein the variable domain that binds to an ellular part of HER2 comprises a heavy chain variable region comprising a CDR1 ce SYGMH, a CDR2 sequence VISYDGSNKYYADSVKG and a CDR3 ce DYYRRTARAGFDY or a variant thereof comprising a conservative substitution of 1, 2, or 3 amino acids in the CDRs, and wherein said heavy chain variable region comprises a common light chain; and - wherein the variable domain that binds to an extracellular part of HER3 comprises a heavy chain variable region comprising a CDR1 sequence GYYMH, a CDR2 sequence WINPNSGGTNYAQKFQG and a CDR3 sequence DHGSRHFWSYWGFDY or a variant thereof comprising a conservative substitution of 1, 2, or 3 amino acids in the CDRs, and wherein said heavy chain variable region comprises a common light chain.
20. The composition of any one of claims 16-19, wherein said common light chain comprises a light chain variable region sing an LCDR1, LCDR2 and LCDR3 amino acid sequence.
21. The composition of any one of claims 16-20, wherein said common light chain comprises the CDR1, CDR2 and CDR3 sequences from the light chain sequence of SEQ ID NO: 10, 11 or 12.
22. The composition of any one of claims 16-21, n said common light chain comprises a light chain le region comprising an LCDR1 comprising the amino acid sequence QSISSY, an LCDR2 comprising the amino acid sequence AAS, and an LCDR3 comprising the amino acid sequence QQSYSTP.
NZ779076A 2020-02-13 Combinations of binding moieties that bind egfr, her2 and her3. NZ779076B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP19157302 2019-02-14
EP19178564 2019-06-05
PCT/NL2020/050081 WO2020167123A1 (en) 2019-02-14 2020-02-13 Combinations of binding moieties that bind egfr, her2 and her3.

Publications (2)

Publication Number Publication Date
NZ779076A NZ779076A (en) 2025-06-27
NZ779076B2 true NZ779076B2 (en) 2025-09-30

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