Methods for treating neurodegenerative disease using anti-PD-1 antibodies

• US 10,618,955 B2
• Filed: 03/29/2018
• Issued: 04/14/2020
• Est. Priority Date: 07/15/2014
• Status: Active Grant

• Current Assignee: Kymab Limited
• Original Assignee: Kymab Limited
• Inventors: Clube, Jasper Rupert
• Primary Examiner(s): Wen, Sharon X
• Application Number:
  US15/939,503
• Publication Number:
  US 20180222977A1
• Time in Patent Office: 747 Days
• Field of Search: None
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/70 containing domain for protein-protein interaction
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

The invention relates to human targets of interest (TOI), anti-TOI ligands, kits compositions and method.

Claims

1. A method of treating or reducing the risk of a neurodegenerative disease in a human, the method comprising administering to said human an anti-PD-1 antibody or antibody fragment that specifically binds to a human PD-1 that is expressed by a PD-1 nucleotide sequence comprising a variation selected from the group consisting of:

rs7568402;

rs28699177;

rs28542728;

rs118117097;

rs28570544;

rs118027315;

rs191919871;

rs6707556;

rs142909968;

rs36084323;

rs10204225;

rs11568821;

rs2227981; and

rs2227982;

wherein the antibody or antibody fragment that specifically binds to human PD-1 comprises;

(i) a human gamma-1 heavy chain constant region that comprises an amino acid selected from the group consisting of;

an Asp corresponding to position 204 of SEQ ID NO;

42 and a Leu corresponding to position 206 of SEQ ID NO;

42;

or

(ii) a human gamma-4 heavy chain constant region that comprises an amino acid selected from the group consisting of;

a Leu corresponding to position 189 of SEQ ID NO;

73 and a Arg corresponding to position 289 of SEQ ID NO;

73; and

wherein the antibody is or antibody fragment comprises the variable domains of an antibody selected from the group consisting of pembrolizumab and nivolumab;

wherein said human comprises;

(iii) an IGHG1*01 human heavy chain constant region gene segment, or the human expresses antibodies comprising human gamma-1 heavy chain constant regions comprising said selected amino acid of clause (i), when the antibody or fragment is according to clause (i);

or

(iv) an IGHG4*01 human heavy chain constant region gene segment, or the human expresses antibodies comprising human gamma-4 heavy chain constant regions comprising said selected amino acid of clause (ii), when the antibody or fragment is according to clause (ii); and

wherein said human comprises;

(v) a PD-1 nucleotide sequence comprising said selected variation; and

wherein the neurodegenerative disease is selected from the group consisting of Alzheimer'"'"'s disease, Parkinson'"'"'s disease, and Huntington'"'"'s disease.

2. The method of claim 1, wherein the selected variation is a nucleotide corresponding to SNP rS1411262, SNP rs4143815, 8923C or 395C.

3. The method of claim 1, wherein said human is homozygous for said variation.

4. The method of claim 1, wherein the antibody or antibody fragment that specifically binds to human PD-1 comprises an IGHG1*01 human heavy chain constant region.

5. The method of claim 1, wherein the antibody or antibody fragment that specifically binds to human PD-1 comprises an IGHG4*01 human heavy chain constant region.

6. The method of claim 1, comprising, before said administering, selecting a human comprising said PD-1 nucleotide sequence of (v), wherein the human is the human of claim 1.

7. The method of claim 1, wherein the human has been determined to comprise said PD-1 nucleotide sequence of (v).

8. The method of claim 1, comprising the step of determining that the human comprises said PD-1 nucleotide sequence of (v), optionally, wherein the determining step is performed before administration of the antibody or antibody fragment that specifically binds to human PD-1 to the human.

9. The method of claim 8, wherein the step of determining comprises assaying a biological sample from the human for a PD-1 nucleotide sequence comprising said selected variation.

10. The method of claim 9, wherein the assaying comprises contacting the biological sample with

a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence comprising said selected variation or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to said selected variation or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence comprising said selected variation is present;

and/or

b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence comprising said selected variation or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises said selected variation thereby forming a complex when the nucleotide sequence comprising said selected variation is present; and

detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises a PD-1 nucleotide sequence comprising said selected variation.

11. The method of claim 9, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.

12. The method of claim 1, wherein said human is or has been further determined to be substantially resistant to a PD-L1 or PD-1 treatment.

13. The method of claim 1, wherein said human is receiving or has received a PD-L1 or PD-1 treatment or has reduced responsiveness to a PD-L1 or PD-1 treatment.

14. The method of claim 9, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.

15. The method of claim 1, wherein said antibody or antibody fragment that specifically binds to human PD-1 is administered by intravenous or subcutaneous injection and/or is comprised in an injectable preparation.

16. The method of claim 1, wherein the antibody or antibody fragment that specifically binds to human PD-1 is a human antibody or antibody fragment.

17. The method of claim 1, wherein the antibody is pembrolizumab or an antibody fragment thereof that specifically binds to a human PD-1.

18. The method of claim 1, wherein the antibody is nivolumab or an antibody fragment thereof that specifically binds to a human PD-1.

19. The method of claim 2, wherein the antibody is pembrolizumab or an antibody fragment thereof that specifically binds to a human PD-1.

20. The method of claim 2, wherein the antibody is nivolumab or an antibody fragment thereof that specifically binds to a human PD-1.