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NZ773949B2 - Anti-PDL1 antibodies, activatable anti-PDL1 antibodies, and methods of use thereof - Google Patents
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NZ773949B2 - Anti-PDL1 antibodies, activatable anti-PDL1 antibodies, and methods of use thereof - Google Patents

Anti-PDL1 antibodies, activatable anti-PDL1 antibodies, and methods of use thereof Download PDF

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Publication number
NZ773949B2
NZ773949B2 NZ773949A NZ77394916A NZ773949B2 NZ 773949 B2 NZ773949 B2 NZ 773949B2 NZ 773949 A NZ773949 A NZ 773949A NZ 77394916 A NZ77394916 A NZ 77394916A NZ 773949 B2 NZ773949 B2 NZ 773949B2
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NZ
New Zealand
Prior art keywords
seq
amino acid
acid sequence
activatable antibody
region
Prior art date
Application number
NZ773949A
Other versions
NZ773949A (en
Inventor
Daniel Hostetter
Li Mei
Stephen James Moore
Margaret Nguyen
Jason Sagert
Jonathan Terrett
Olga Vasiljeva
James William West
Original Assignee
Cytomx Therapeutics Inc
Filing date
Publication date
Application filed by Cytomx Therapeutics Inc filed Critical Cytomx Therapeutics Inc
Publication of NZ773949A publication Critical patent/NZ773949A/en
Publication of NZ773949B2 publication Critical patent/NZ773949B2/en

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    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
    • A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
    • A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
    • A61K49/0041—Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
    • A61K49/0058—Antibodies
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • C07K16/2827—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 B7 molecules, e.g. CD80, CD86
    • 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
    • C07K2317/50—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
    • 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
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • 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
    • 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
    • C07K2317/70—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 relates generally to antibodies that bind programmed death ligand 1 (PDL1), activatable antibodies that specifically bind to PDL1 and methods of making and using these anti-PDL1 antibodies and anti-PDL1 activatable antibodies in a variety of therapeutic, diagnostic and prophylactic indications. A particular embodiment includes the isolated nucleic acid molecules encoding an antibody that comprise the following heavy chain CDRs: SYAMS (CDR1, SEQ ID NO: 212), SSIWRNGIVTVYADS (CDR2, SEQ ID NO: 246) and WSAAFDY (CDR3, SEQ ID NO: 235); and comprise the following light chain CDRs: RASQSISSYLN (CDR1, SEQ ID NO: 209), AASSLQS (CDR2, SEQ ID NO: 215) or DGAGFDY (CDR2, SEQ ID NO: 222), and DNGYPST (CDR3, SEQ ID NO: 228). In a particular embodiment this activatable antibody comprises a masking moiety (MM) a cleavable moiety (CM).

Claims (26)

Claims
1. An isolated nucleic acid molecule encoding an antibody or an antigen g fragment thereof (AB) comprising: (a) a heavy chain variable region (VH) comprising: (i) a variable heavy chain complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SEQ ID NO: 212; (ii) a variable heavy chain complementarity determining region 2 (VH CDR2) comprising the amino acid sequence of SEQ ID NO: 246; and (iii) a variable heavy chain complementarity determining region 3 (VH CDR3) comprising the amino acid sequence of SEQ ID NO: 235; and (b) a light chain le region (VL) comprising: (i) a variable light chain complementarity region 1 (VL CDR1) comprising the amino acid sequence of SEQ ID NO: 209; (ii) a variable light chain complementarity region 2 (VL CDR2) comprising the amino acid ce of SEQ ID NO: 215 or 227; and (iii) a variable light chain complementarity region 3 (VL CDR3) comprising the amino acid ce of SEQ ID NO: 228; wherein the AB specifically binds mammalian PDL1.
2. An ed nucleic acid molecule encoding an activatable dy comprising: (a) an antibody or antigen binding fragment thereof (AB) that specifically binds to mammalian PDL1, n the AB comprises: (i) a heavy chain variable region (VH) comprising: a variable heavy chain complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SEQ ID NO: 212; a variable heavy chain complementarity determining region 2 (VH CDR2) comprising the amino acid sequence of SEQ ID NO: 246; and a variable heavy chain complementarity determining region 3 (VH CDR3) comprising the amino acid sequence of SEQ ID NO: 235; and (ii) a light chain variable region (VL) comprising: a light chain variable complementarity region 1 (VL CDR1) comprising the amino acid sequence of SEQ ID NO: 209; a light chain variable complementarity region 2 (VL CDR2) comprising the amino acid sequence of SEQ ID NO: 215 or 227; and a light chain variable complementarity region 3 (VL CDR3) comprising the amino acid sequence of SEQ ID NO: 228; and (b) a masking moiety (MM) comprising the amino acid sequence of SEQ ID NO: 63; and (c) a cleavable moiety (CM) comprising the amino acid sequence of SEQ ID NO: 377.
3. The isolated nucleic acid of claim 2, wherein the MM does not interfere or compete with the AB for binding to PDL1 when the activatable antibody is in a cleaved state.
4. The isolated nucleic acid of claim 2, wherein the CM is a substrate for a protease that is active in diseased tissue.
5. The ed c acid of claim 2, n the MM is linked to the CM such that the activatable antibody in an uncleaved state comprises the structural ement from N-terminus to C-terminus as follows: MM-CM-AB or AB-CM-MM.
6. The isolated nucleic acid of claim 5, wherein the activatable antibody comprises a linking peptide between the MM and the CM.
7. The ed c acid of claim 5, wherein the activatable antibody comprises a linking peptide between the CM and the AB.
8. The isolated nucleic acid of claim 5, n the activatable antibody comprises a first linking peptide (LP1) and a second linking peptide (LP2), and wherein the activatable antibody in the uncleaved state has the structural arrangement from N-terminus to C-terminus as follows: MMLP1-CM-LP2-AB or AB-LP2-CM-LP1-MM.
9. The isolated nucleic acid of claim 8, wherein the two linking peptides are not identical to each other.
10. The ed c acid of any one of claims 1 - 9, n the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 215.
11. The isolated nucleic acid of any one of claims 1 - 9, wherein the AB comprises a VH comprising the amino acid sequence of SEQ ID NO: 46 and a VL comprising the amino acid sequence of SEQ ID NO: 12.
12. The isolated nucleic acid of any one of claims 1 - 9, wherein the AB comprises a VH comprising the comprising the amino acid sequence of SEQ ID NO: 46 and a VL comprising the amino acid sequence of SEQ ID NO: 58.
13. The isolated nucleic acid of any one of claims 1 - 9, wherein the activatable antibody comprises a VL comprising the amino acid sequence of SEQ ID NO: 137 and a VH sing the amino acid sequence of SEQ ID NO: 46.
14. The isolated nucleic acid of any one of claims 1 - 9, wherein the activatable antibody comprises a VL comprising the amino acid sequence of SEQ ID NO: 985 and a VH comprising the amino acid sequence of SEQ ID NO: 46.
15. The ed nucleic acid of any one of claims 1 - 9, wherein the activatable antibody comprises a VL comprising the amino acid sequence of SEQ ID NO: 428 and a VH comprising the amino acid sequence of SEQ ID NO: 432.
16. The ed nucleic acid of any one of claims 1 - 9, wherein the activatable antibody comprises a VL comprising the amino acid sequence of SEQ ID NO: 1008 and a VH comprising the amino acid sequence of SEQ ID NO: 432.
17. A method of manufacturing a multispecific activatable antibody, the method comprising (a) ing a cell comprising a nucleic acid construct that encodes the multispecific activatable antibody or antigen binding fragment thereof that specifically binds ian PDL1 under conditions that lead to expression of the pecific activatable antibody or antigen binding nt thereof, wherein the multispecific activatable antibody or antigen binding fragment thereof comprises: (i) a heavy chain variable region (VH) comprising: i. a variable heavy chain complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SEQ ID NO: 212; ii. a variable heavy chain complementarity determining region 2 (VH CDR2) comprising the amino acid sequence of SEQ ID NO: 246; iii. a variable heavy chain complementarity determining region 3 (VH CDR3) comprising the amino acid ce of SEQ ID NO: 235; and (ii) a light chain variable region (VL) comprising: i. a variable light chain complementarity determining region 1 (VL CDR1) comprising the amino acid sequence of SEQ ID NO: 209; ii. a variable light chain complementarity determining region 2 (VL CDR2) comprising an amino acid sequence of SEQ ID NOs: 215 or 227; and iii. a variable light chain mentarity determining region 3 (VL CDR3) comprising the amino acid sequence of SEQ ID NO: 228; and (b) recovering the pecific table antibody.
18. A method of manufacturing a multispecific activatable antibody, the method comprising (a) culturing a cell comprising a nucleic acid construct that encodes the multispecific activatable antibody or antigen binding fragment thereof that specifically binds mammalian PDL1 under conditions that lead to expression of the multispecific activatable antibody or antigen binding nt thereof, n the multispecific activatable antibody or antigen binding fragment thereof comprises: (i) a heavy chain variable region (VH) comprising: i. a variable heavy chain complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SEQ ID NO: 212; ii. a variable heavy chain complementarity determining region 2 (VH CDR2) comprising the amino acid sequence of SEQ ID NO: 246; iii. a variable heavy chain mentarity determining region 3 (VH CDR3) comprising the amino acid sequence of SEQ ID NO: 235; and (ii) a light chain variable region (VL) comprising: i. a variable light chain complementarity determining region 1 (VL CDR1) comprising the amino acid sequence of SEQ ID NO: 209; ii. a le light chain complementarity determining region 2 (VL CDR2) comprising an amino acid sequence of SEQ ID NOs: 215 or 227; and iii. a variable light chain complementarity determining region 3 (VL CDR3) sing the amino acid ce of SEQ ID NO: 228; and (iii) a masking moiety (MM) comprising the amino acid sequence of SEQ ID NO: 63; (iv) a cleavable moiety (CM) comprising the amino acid sequence of SEQ ID NO: 377; (b) recovering the multispecific activatable antibody.
19. The method of claim 17 or 18, wherein the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 215.
20. The method of claim 17 or 18, wherein the AB comprises a VH comprising the amino acid sequence of SEQ ID NO: 46 and a VL comprising the amino acid sequence of SEQ ID NO: 12.
21. The method of claim 17 or 18, wherein the AB comprises a VH comprising the comprising the amino acid sequence of SEQ ID NO: 46 and a VL sing the amino acid sequence of SEQ ID NO: 58.
22. The method of claim 17 or 18, wherein the activatable dy comprises a VL comprising the amino acid sequence of SEQ ID NO: 137 and a VH comprising the amino acid sequence of SEQ ID NO: 46.
23. The method of claim 17 or 18, wherein the activatable antibody comprises a VL comprising the amino acid sequence of SEQ ID NO: 985 and a VH comprising the amino acid sequence of SEQ ID NO: 46.
24. The method of claim 17 or 18, wherein the activatable antibody ses a VL comprising the amino acid sequence of SEQ ID NO: 428 and a VH comprising the amino acid sequence of SEQ ID NO: 432.
25. The method of claim 17 or 18, wherein the activatable antibody comprises a VL sing the amino acid sequence of SEQ ID NO: 1008 and a VH comprising the amino acid sequence of SEQ ID NO: 432.
26. The method of any one of claims 17 - 25, wherein the multispecific activatable dy or antigen binding fragment thereof is a bispecific antibody. CytomX Therapeutics, Inc. By the Attorneys for the Applicant SPRUSON & FERGUSON
NZ773949A 2016-03-14 Anti-PDL1 antibodies, activatable anti-PDL1 antibodies, and methods of use thereof NZ773949B2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201562133231P 2015-03-13 2015-03-13
US201562139596P 2015-03-27 2015-03-27
US201562218883P 2015-09-15 2015-09-15
NZ736142A NZ736142B2 (en) 2015-03-13 2016-03-14 Anti-pdl1 antibodies, activatable anti-pdl1 antibodies, and methods of use thereof

Publications (2)

Publication Number Publication Date
NZ773949A NZ773949A (en) 2024-03-22
NZ773949B2 true NZ773949B2 (en) 2024-06-25

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