Methods for treating neurodegenerative diseases using anti-PD-L1 antibodies
First Claim
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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-L1 antibody or antibody fragment that specifically binds to a human PD-L1 that is expressed by a PD-L1 nucleotide sequence comprising a variation selected from the group consisting of:
- rs1411262;
rs4143815;
8923C;
rs150439231;
rs138261640;
rs142983488;
rs76741468;
rs822336;
rs183400620;
rs187252832;
rs146143976;
rs139023765;
rs73641615;
rs17718883;
rs139709512;
rs140045210;
rs141978642;
rs146495642;
rs370800260;
rs143235887;
rs373692552;
rs140304675;
rs12551333;
rs376993991;
rs367921713;
rs41280721;
rs61752860;
rs148141792;
rs369350813;
rs10481593;
rs2282055;
rs2297135;
rs2297136;
rs2297137;
rs3780395;
rs7023227;
rs1411262;
rs34028061;
rs7041009;
rs148170925;
rs10114060;
rs1536926; and
rs7042084;
wherein the antibody or antibody fragment that specifically binds to human PD-L1 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-1 heavy chain constant region that comprises an amino acid selected from the group consisting of;
an Glu corresponding to position 204 of SEQ ID NO;
42 and a Met corresponding to position 206 of SEQ ID NO;
42;
or(iii) 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 an Arg corresponding to position 289 of SEQ ID NO;
73; and
wherein the antibody or antibody fragment comprises the variable domains of an antibody selected from the group consisting of;
durvalumab, atezolizumab, STI-A1014, avelumab, and BMS-936559; and
wherein said human comprises;
(iv) 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(v) an IGHG1*03 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 (ii), when the antibody or fragment is according to clause (ii);
or(vi) 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 (iii), when the antibody or fragment is according to clause (iii); and
wherein said human comprises;
(vii) a PD-L1 nucleotide sequence comprising said selected variation,wherein the neurodegenerative disease is selected from the group consisting of Alzheimer'"'"'s disease, Parkinson'"'"'s disease, and Huntington'"'"'s disease.
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Abstract
The invention relates to human targets of interest (TOI), anti-TOI ligands, kits compositions and method.
158 Citations
21 Claims
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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-L1 antibody or antibody fragment that specifically binds to a human PD-L1 that is expressed by a PD-L1 nucleotide sequence comprising a variation selected from the group consisting of:
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rs1411262;
rs4143815;
8923C;
rs150439231;
rs138261640;
rs142983488;
rs76741468;
rs822336;
rs183400620;
rs187252832;
rs146143976;
rs139023765;
rs73641615;
rs17718883;
rs139709512;
rs140045210;
rs141978642;
rs146495642;
rs370800260;
rs143235887;
rs373692552;
rs140304675;
rs12551333;
rs376993991;
rs367921713;
rs41280721;
rs61752860;
rs148141792;
rs369350813;
rs10481593;
rs2282055;
rs2297135;
rs2297136;
rs2297137;
rs3780395;
rs7023227;
rs1411262;
rs34028061;
rs7041009;
rs148170925;
rs10114060;
rs1536926; and
rs7042084;wherein the antibody or antibody fragment that specifically binds to human PD-L1 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-1 heavy chain constant region that comprises an amino acid selected from the group consisting of; an Glu corresponding to position 204 of SEQ ID NO;
42 and a Met corresponding to position 206 of SEQ ID NO;
42;
or(iii) 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 an Arg corresponding to position 289 of SEQ ID NO;
73; andwherein the antibody or antibody fragment comprises the variable domains of an antibody selected from the group consisting of; durvalumab, atezolizumab, STI-A1014, avelumab, and BMS-936559; and wherein said human comprises; (iv) 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(v) an IGHG1*03 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 (ii), when the antibody or fragment is according to clause (ii);
or(vi) 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 (iii), when the antibody or fragment is according to clause (iii); and wherein said human comprises; (vii) a PD-L1 nucleotide sequence comprising said selected variation, wherein the neurodegenerative disease is selected from the group consisting of Alzheimer'"'"'s disease, Parkinson'"'"'s disease, and Huntington'"'"'s disease. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)
(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-L1 nucleotide sequence comprising said selected variation.
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12. 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.
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13. The method of claim 9, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.
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14. 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.
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15. 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.
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16. The method of claim 1, wherein said antibody or antibody fragment that specifically binds to human PD-L1 is administered by intravenous or subcutaneous injection and/or is comprised in an injectable preparation.
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17. The method of claim 1, wherein the antibody or antibody fragment that specifically binds to human PD-L1 is a human antibody or antibody fragment.
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18. The method of claim 1, wherein the antibody is atezolizumab or an antibody fragment thereof that specifically binds to a human PD-L1.
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19. The method of claim 1, wherein the antibody is durvalumab or an antibody fragment thereof that specifically binds to a human PD-L1.
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20. The method of claim 2, wherein the antibody is atezolizumab or an antibody fragment thereof that specifically binds to a human PD-L1.
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21. The method of claim 2, wherein the antibody is durvalumab or an antibody fragment thereof that specifically binds to a human PD-L1.
Specification