1. A method of treating a solid tumor; melanoma; renal cell carcinoma; non small-cell lung cancer; bladder cancer; Hodgkin’s lymphoma; or gastric cancer 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;
wherein the antibody or antibody fragment that specifically binds to human PD-L1 comprises 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; and
wherein said human comprises:
(i) 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; and
(ii) a PD-L1 nucleotide sequence comprising said selected variation.
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 humanPD-L1 comprises an IGHG1*01 human heavy chain constant region.
5. The method of claim 1, comprising, before said administering, selecting a human comprising said PD-L1 nucleotide sequence of (ii), wherein the human is the human of claim 1.
6. The method of claim 1, wherein the human has been determined to comprise said PD-L1 nucleotide sequence of (ii).
7. The method of claim 1, comprising the step of determining that the human comprises said PD-L1 nucleotide sequence of (ii), optionally, wherein the determining step is performed before administration of the antibody or antibody fragment that specifically binds to human PD-L1 to the human.
8. The method of claim 7, wherein the step of determining comprises assaying a biological sample from the human for a PD-L1 nucleotide sequence comprising said selected variation.
9. The method of claim 8, 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; andor
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.
10. 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 andor wherein the assaying is performed in a multiplex format.
11. The method of claim 1, wherein said human is or has been further determined to be substantially resistant a PD-L1 or PD-1 treatment.
12. 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.
13. The method of claim 8, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine andor saliva of said human.
14. 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 andor is comprised in an injectable preparation.
15. 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.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
What is claimed is:
1. A maskant used in aluminiding a surface of a metallic substrate, the metallic substrate having a substrate surface composition comprising nickel, a substrate aluminum content, and other alloying elements, the maskant including
a plurality of maskant particles, each maskant particle having a maskant particle composition comprising a maskant metal selected from the group consisting of nickel, cobalt, titanium, chromium, iron, and combinations thereof, and a maskant aluminum content.
2. The maskant of claim 1, wherein the maskant aluminum content is about the same as the substrate aluminum content.
3. The maskant of claim 1, wherein the particle composition is substantially the same as the substrate surface composition.
4. The maskant of claim 1, wherein the plurality of maskant particles are distributed substantially uniformly throughout the maskant.
5. The maskant of claim 1, wherein the maskant has a first surface and a second surface, and wherein the plurality of maskant particles are distributed nonuniformly throughout the maskant such that there are more maskant particles adjacent to the first surface than to the second surface.
6. The maskant of claim 1, further including
a plurality of nickel particles, each nickel particle having a nickel composition comprising nickel and substantially no aluminum.
7. The maskant of claim 1, wherein the maskant further comprises a binder in which the maskant particles are distributed.
8. The maskant of claim 1, wherein the maskant comprises
a maskant particle layer comprising the maskant particles overlying and contacting the surface, and
a maskant layer overlying the particle layer, the maskant layer comprising other metallic particles.
9. The maskant of claim 1, wherein the maskant aluminum content is from about 0.3 to about 30 percent by weight of the maskant particles.
10. The maskant of claim 1, wherein the maskant aluminum content is from about 5 to about 7 percent by weight of the maskant particles.
11. A method for aluminiding a surface comprising the steps of
providing a metallic substrate having a substrate surface, the metallic substrate having a substrate surface composition comprising nickel, a substrate aluminum content, and other alloying elements;
applying a maskant overlying a protected region of the substrate surface to produce a masked substrate surface having an exposed region and the protected region, the maskant comprising a plurality of maskant particles, each particle having a maskant particle composition comprising a maskant metal selected from the group consisting of nickel, cobalt, titanium, chromium, iron, and combinations thereof, and a maskant aluminum content; and
contacting a source of aluminum to the masked substrate surface, whereby aluminum deposits on the exposed region and does not deposit on the protected region.
12. The method of claim 11, wherein the maskant aluminum content is about the same as the substrate aluminum content.
13. The method of claim 11, wherein the particle composition is substantially the same as the substrate surface composition.
14. The method of claim 11, wherein the plurality of maskant particles are distributed substantially uniformly throughout the maskant.
15. The method of claim 11, wherein the maskant has a first surface and a second surface, and wherein the plurality of maskant particles are distributed nonuniformly throughout the maskant such that there are more maskant particles adjacent to the first surface than to the second surface.
16. The method of claim 11, further including
a plurality of nickel particles, each nickel particle having a nickel composition comprising nickel and substantially no aluminum.
17. The method of claim 1, wherein the maskant further comprises a binder in which the maskant particles are distributed.
18. The method of claim 11, wherein the maskant comprises
a maskant particle sublayer comprising the maskant particles overlying and contacting the substrate surface, and
a maskant sublayer overlying the particle layer, the maskant layer comprising other metallic particles.
19. The method of claim 11, wherein the source of aluminum comprises an aluminum-containing gas.