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NZ741686B2 - Combination therapy using inhibitors of human growth and differentiation factor 15 (gdf-15) and immune checkpoint blockers - Google Patents
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NZ741686B2 - Combination therapy using inhibitors of human growth and differentiation factor 15 (gdf-15) and immune checkpoint blockers - Google Patents

Combination therapy using inhibitors of human growth and differentiation factor 15 (gdf-15) and immune checkpoint blockers

Info

Publication number
NZ741686B2
NZ741686B2 NZ741686A NZ74168616A NZ741686B2 NZ 741686 B2 NZ741686 B2 NZ 741686B2 NZ 741686 A NZ741686 A NZ 741686A NZ 74168616 A NZ74168616 A NZ 74168616A NZ 741686 B2 NZ741686 B2 NZ 741686B2
Authority
NZ
New Zealand
Prior art keywords
cancer
hgdf
inhibitor
cells
immune checkpoint
Prior art date
Application number
NZ741686A
Other versions
NZ741686A (en
Inventor
Reinhard Dummer
Markus Haake
Matthias Mehling
Tina Schafer
Martina Selle
Jorg Wischhusen
Original Assignee
Julius Maximilians Universität Würzburg
Filing date
Publication date
Priority claimed from GBGB1517531.8A external-priority patent/GB201517531D0/en
Priority claimed from GBGB1607801.6A external-priority patent/GB201607801D0/en
Application filed by Julius Maximilians Universität Würzburg filed Critical Julius Maximilians Universität Würzburg
Priority to NZ776574A priority Critical patent/NZ776574B2/en
Priority claimed from PCT/EP2016/073520 external-priority patent/WO2017055613A2/en
Publication of NZ741686A publication Critical patent/NZ741686A/en
Publication of NZ741686B2 publication Critical patent/NZ741686B2/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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • 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
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • C07K16/22—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
    • C07K16/28—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
    • C07K16/2818—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 CD28 or CD152
    • 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
    • C07K16/2878—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-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • 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
    • C07K2317/70—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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/10—Screening for compounds of potential therapeutic value involving cells
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5047—Cells of the immune system
    • G01N33/505—Cells of the immune system involving T-cells
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5064—Endothelial cells
    • G01N33/574—

Abstract

The present invention relates to uses of inhibitors of human Growth and Differentiation Factor 15 (GDF-15), particularly anti-hGDF-15 antibodies, and to combined uses of such inhibitors with immune checkpoint blockers, particularly anti-PD-1 or anti-PD-L1 antibodies, in the treatment of solid cancers.

Claims (16)

WE CLAIM:
1. Use of an hGDF-15 inhibitor in the manufacture of a medicament for increasing the percentage of CD8 T-cells in a solid cancer in a human patient, wherein the medicament is for the treatment of cancer, wherein the hGDF-15 inhibitor is to be administered with a cancer immunotherapy, wherein the hGDF-15 inhibitor is a monoclonal antibody capable of binding to hGDF-15, or an antigen-binding portion thereof, and wherein the cancer immunotherapy is one or more immune checkpoint blocker selected from the group consisting of: i) an inhibitor of human PD-1, the inhibitor being a monoclonal antibody capable of binding to human PD-1, or an antigen-binding portion thereof; ii) an inhibitor of human PD-L1, the inhibitor being a monoclonal antibody capable of binding to human PD-L1, or an antigen-binding portion thereof.
2. The use according to claim 1, wherein the patient is a patient who has a hGDF-15 serum level of at least 1.2 ng/ml prior to the start of administration of the hGDF-15 inhibitor, wherein the patient is preferably a patient who has a hGDF-15 serum level of at least 1.5 ng/ml prior to the start of administration of the hGDF-15 inhibitor, and wherein the patient is more preferably a patient who has a hGDF-15 serum level of at least 1.8 ng/ml prior to the start of administration of the hGDF-15 inhibitor; and/or wherein the cancer is selected from the group consisting of melanoma, colorectal cancer, prostate cancer, head and neck cancer, urothelial cancer, stomach cancer, pancreatic cancer, liver cancer, testis cancer, ovarian cancer, endometrial cancer, cervical cancer, brain cancer, breast cancer, gastric cancer, renal cell carcinoma, Ewing’s sarcoma, non-small cell lung cancer and small cell lung cancer, wherein the cancer is preferably selected from the group consisting of melanoma, colorectal cancer, prostate cancer, head and neck cancer, urothelial cancer, stomach cancer, pancreatic cancer, liver cancer, testis cancer, ovarian cancer, endometrial cancer and cervical cancer, and wherein the cancer is more preferably selected from the group consisting of melanoma, colorectal cancer, prostate cancer, head and neck cancer, urothelial cancer and stomach cancer; and/or wherein the cancer is selected from the group consisting of melanoma, oral squamous cell carcinoma, colorectal cancer and prostate cancer.
3. The use according to any one of the preceding claims, wherein (i) the binding to hGDF-15 is binding to a conformational or discontinuous epitope on hGDF-15, and wherein the conformational or discontinuous epitope comprises the amino acid sequences of SEQ ID No: 25 and SEQ ID No: 26, and/or wherein (ii) the antibody or antigen-binding portion thereof comprises a heavy chain variable domain which comprises a CDR1 region comprising the amino acid sequence of SEQ ID NO: 3, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 4 and a CDR3 region comprising the amino acid sequence of SEQ ID NO: 5, and wherein the antibody or antigen-binding portion thereof comprises a light chain variable domain which comprises a CDR1 region comprising the amino acid sequence of SEQ ID NO: 6, a CDR2 region comprising the amino acid sequence ser-ala-ser and a CDR3 region comprising the amino acid sequence of SEQ ID NO: 7.
4. The use according to any one of the preceding claims, wherein the treatment of the solid cancer is a treatment of cancer metastases, and/or wherein the hGDF-15 inhibitor increases the percentage of CD8 T-cells in the cancer by increasing the adhesion of CD8 T-cells to endothelial cells and thereby increasing entry of the CD8 T-cells from the blood stream into the cancer.
5. Use of a composition comprising an hGDF-15 inhibitor and an immune checkpoint blocker in the manufacture of a medicament, wherein the hGDF-15 inhibitor is as defined in claim 1, and wherein the immune checkpoint blocker is as defined in claim 1.
6. Use of a kit comprising an hGDF-15 inhibitor and at least one immune checkpoint blocker in the manufacture of a medicament, wherein the hGDF-15 inhibitor is as defined in claim 1, and wherein the immune checkpoint blocker is as defined in claim 1.
7. The use according to claim 6, wherein the hGDF-15 inhibitor and one or more or all of the immune checkpoint blockers are contained in separate containers or in a single container.
8. Use according to any one of claims 5 to 7, wherein the medicament is a medicament for treating a solid cancer, wherein the medicament is for cancer immunotherapy and wherein the cancer is preferably as defined in claim 2.
9. Use of an hGDF-15 inhibitor in the manufacture of a medicament for treating a solid cancer in combination with an immune checkpoint blocker in a human patient, wherein the hGDF-15 inhibitor is to be administered with the immune checkpoint blocker, wherein the hGDF-15 inhibitor is as defined in claim 1, and wherein the immune checkpoint blocker is as defined in claim 1.
10. The use according to claim 9, wherein the patient is as defined in claim 2, and/or wherein the cancer is as defined in claim 2, and/or wherein the hGDF-15 inhibitor increases the percentage of CD8 T-cells in the cancer, preferably by increasing the adhesion of CD8 T-cells to endothelial cells or the rolling of CD8 T cells on endothelial cells and thereby increasing entry of the CD8 T- cells from the blood stream into the cancer.
11. Use of a combination of an hGDF-15 inhibitor and an immune checkpoint blocker in the manufacture of a medicament for treating a solid cancer in a human patient, wherein the hGDF-15 inhibitor is as defined in claim 1, and wherein the immune checkpoint blocker is as defined in claim 1.
12. The use according to claim 11, wherein the patient is as defined in claim 2, and/or wherein the cancer is as defined in claim 2, and/or wherein the hGDF-15 inhibitor increases the percentage of CD8 T-cells in the cancer, preferably by increasing the adhesion of CD8 T-cells to endothelial cells, thereby increasing entry of the CD8 T-cells from the blood stream into the solid cancer, and wherein preferably, said increase in adhesion of CD8 T-cells to endothelial cells increases the rolling of CD8 T cells on endothelial cells such that said entry of the CD8 T-cells from the blood stream into the solid cancer is increased.
13. The use according to any one of claims 1-4, wherein the medicament is to be administered in combination with polyinosinic:polycytidylic acid, or the use according to any one of claims 11-12, wherein the combination is a combination with polyinosinic:polycytidylic acid.
14. The use according to any one of claims 1-4 and 13, wherein the medicament is to be administered in combination with an anti-human CD40 antibody, preferably a monoclonal anti-human CD40 antibody, or the use according to any one of claims 11-13, wherein the combination is a combination with an anti-human CD40 antibody, preferably a monoclonal anti-human CD40 antibody.
15. The use according to any one of claims 1-4, wherein the hGDF-15 inhibitor and the immune checkpoint blocker are to be administered together.
16. The use according to any one of claims 1-4, wherein the hGDF-15 inhibitor and the immune checkpoint blocker are to be administered separately.
NZ741686A 2016-09-30 Combination therapy using inhibitors of human growth and differentiation factor 15 (gdf-15) and immune checkpoint blockers NZ741686B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
NZ776574A NZ776574B2 (en) 2016-09-30 Combination therapy using inhibitors of human growth and differentiation factor 15 (GDF-15) and immune checkpoint blockers

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB1517531.8A GB201517531D0 (en) 2015-10-02 2015-10-02 Combination therapy using inhibitors of human growth and differentiation factor 15 (GDF-15) and immune checkpoint blockers
GBGB1607801.6A GB201607801D0 (en) 2016-04-29 2016-04-29 Combination therapy using inhibitors of human Growth and Differentiation Factor 15 (GDF-15) and immune checkpoint blockers
PCT/EP2016/073520 WO2017055613A2 (en) 2015-10-02 2016-09-30 Combination therapy using inhibitors of human growth and differentiation factor 15 (gdf-15) and immune checkpoint blockers

Publications (2)

Publication Number Publication Date
NZ741686A NZ741686A (en) 2025-03-28
NZ741686B2 true NZ741686B2 (en) 2025-07-01

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