NZ755446B2 - Early detection of glial cell activation in neurodegenerative or neuroinflammatory diseases - Google Patents

Early detection of glial cell activation in neurodegenerative or neuroinflammatory diseases

Info

Publication number
NZ755446B2
NZ755446B2 NZ755446A NZ75544618A NZ755446B2 NZ 755446 B2 NZ755446 B2 NZ 755446B2 NZ 755446 A NZ755446 A NZ 755446A NZ 75544618 A NZ75544618 A NZ 75544618A NZ 755446 B2 NZ755446 B2 NZ 755446B2
Authority
NZ
New Zealand
Prior art keywords
seq
subject
medicament
amino acid
sema4d
Prior art date
Application number
NZ755446A
Other versions
NZ755446A (en
Inventor
Maurice Zauderer
Original Assignee
Vaccinex Inc
Filing date
Publication date
Application filed by Vaccinex Inc filed Critical Vaccinex Inc
Priority claimed from PCT/US2018/018794 external-priority patent/WO2018156509A1/en
Publication of NZ755446A publication Critical patent/NZ755446A/en
Publication of NZ755446B2 publication Critical patent/NZ755446B2/en

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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
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • 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
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], 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
    • 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
    • C07K2317/76—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
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/28—Neurological disorders
    • G01N2800/2814—Dementia; Cognitive disorders
    • G01N2800/2821—Alzheimer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/28—Neurological disorders
    • G01N2800/2835—Movement disorders, e.g. Parkinson, Huntington, Tourette
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
    • 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
    • G01N33/66—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood sugars, e.g. galactose
    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6854—Immunoglobulins
    • G01N33/6857—Antibody fragments
    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G01N33/6896—Neurological disorders, e.g. Alzheimer's disease

Abstract

The disclosure provides a method for determining the efficacy of treatment with a SEMA4D antagonist, e.g., a SEMA4D antagonist antibody in the treatment of a neuroinflammatory or neurodegenerative disease, disorder, or injury, where the method provides differential measurement of glucose uptake in the brain, e.g., by FDG-PET imaging.

Claims (20)

WHAT IS CLAIMED IS:
1. Use of a semaphorin 4D (SEMA4D) antagonist antibody or antigen-binding fragment thereof for the preparation of a medicament for treating a subject having, suspected of having, or at risk of developing a neurodegenerative or neuroinflammatory disease, disorder, or injury, wherein the SEMA4D antagonist antibody comprises a VH and a VL, wherein the VH comprises three complementarity determining regions (CDRs) HCDR1, HCDR2, and HCDR3, wherein the VL comprises three CDRs LCDR1, LCDR2, and LCDR3, and wherein the CDRs comprise the amino acid sequences SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8, respectively; and wherein the medicament is characterized in that: i. the medicament is to be used such that administration of the medicament is to be continued if as compared to baseline of glucose uptake in the subject’s brain measured prior to administration of the medicament, an increase in glucose uptake in the subject’s brain measured after administration of the medicament over said baseline is detected; or ii. the medicament is to be used such that administration of the medicament is to be discontinued if as compared to baseline of glucose uptake in the subject’s brain measured prior to administration of the medicament, no change or a decrease in glucose uptake in the subject’s brain measured after administration of the medicament is detected.
2. The use of claim 1, wherein the SEMA4D antagonist antibody or fragment thereof inhibits SEMA4D interaction with its receptor.
3. The use of claim 2, wherein the receptor is Plexin-B1, Plexin-B2, or CD72.
4. The use of any one of claims 1-3, wherein the SEMA4D antagonist antibody or fragment thereof inhibits SEMA4D-mediated Plexin-B1 signal transduction.
5. The use of any one of claims 1-4, wherein the SEMA4D antagonist antibody or fragment thereof competitively inhibits a reference antibody, wherein the reference antibody comprises a variable heavy chain region (VH) comprising the amino acid sequence SEQ ID NO: 1 and a variable light chain region (VL) comprising the amino acid sequence SEQ ID NO: 5 from binding to SEMA4D.
6. The use of any one of claims 1 to 5, wherein the SEMA4D antagonist antibody or fragment thereof binds to the same SEMA4D epitope as a reference antibody wherein the reference antibody comprises a VH comprising the amino acid sequence SEQ ID NO: 1 and a VL comprising the amino acid sequence SEQ ID NO: 5.
7. The use of any one of claims 1 to 6, wherein the CDRs comprise the amino acid sequences SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8, respectively.
8. The use of any one of claims 1 to 7, wherein the VH comprises an amino acid sequence at least 90% identical to SEQ ID NO: 1 and the VL comprises an amino acid sequence at least 90% identical to SEQ ID NO: 5.
9. The use of claim 1, wherein the VH comprises the amino acid sequence SEQ ID NO: 1 and the VL comprises the amino acid sequence SEQ ID NO: 5.
10. The use of claim 1, wherein the baseline measurement of glucose uptake is measured just prior to administration of a first dose of the SEMA4D antagonist antibody.
11. The use of claim 10 wherein the change in glucose uptake relative to baseline is measured at least one week after the first dose, at least two weeks after the first dose, at least one month after the first dose, at least two months after the first dose, at least three months after the first dose, at least four months after the first dose, at least five months after the first dose, at least six months after the first dose, or any combination thereof.
12. The use of any one of claims 1 to 11, wherein glucose uptake in the subject’s brain is measured by 18F- Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) imaging.
13. The use of any one of claims 1 to 12, wherein the neurodegenerative or neuroinflammatory disease, disorder or injury is Alzheimer's disease, Parkinson's disease, Huntington's disease, Down syndrome, ataxia, amyotrophic lateral sclerosis (ALS), multiple sclerosis, (MS), epilepsy, meningitis, brain edema, spinal cord injury, traumatic brain injury, frontotemporal dementia (FTD), HIV-related cognitive impairment, CNS Lupus, mild cognitive impairment, or a combination thereof.
14. The use of claim 13 wherein the neurodegenerative or neuroinflammatory disease, disorder or injury is Huntington’s disease (HD).
15. The use of claim 14, wherein the subject is at risk of developing HD due to familial history of HD or genetic testing.
16. The use of claim 15, wherein genetic testing reveals 36 or more CAG repeats in the subject’s HTT gene.
17. The use of any one of claims 14 to 16, wherein the subject is suspected of having HD due to mild motor dysfunction, mild cognitive impairment, or mild neuropsychiatric features.
18. The use of any one of claims 14 to 17, wherein the subject is diagnosed as having HD due to brain atrophy, an elevated Uniform Huntington’s Disease Rating Scale score (UHDRS), an increased Huntington’s Disease Cognitive Assessment Battery (HD-CAB) score, an increased Huntington’s Disease Quantitative Motor Assessment score or a combination thereof.
19. The use of claim 19, wherein the subject is in the presymptomatic, early prodromal, late prodromal, early manifest, moderate manifest, or advanced manifest stage of HD.
20. The use according to any one of claims 1 to 19, substantially as herein described and with reference to any example thereof and with reference to the figures.
NZ755446A 2018-02-20 Early detection of glial cell activation in neurodegenerative or neuroinflammatory diseases NZ755446B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201762461945P 2017-02-22 2017-02-22
PCT/US2018/018794 WO2018156509A1 (en) 2017-02-22 2018-02-20 Early detection of glial cell activation in neurodegenerative or neuroinflammatory diseases

Publications (2)

Publication Number Publication Date
NZ755446A NZ755446A (en) 2025-06-27
NZ755446B2 true NZ755446B2 (en) 2025-09-30

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