	US 12,070,460 B2
	Methods of treating skin cancer with Carboxypeptidase Vitellogenic Like (CPVL) inhibitors
Xinyuan Zhang, Tarrytown, NY (US); Julie Horowitz, Tarrytown, NY (US); Stefan Semrau, Tarrytown, NY (US); Goncalo Abecasis, Tarrytown, NY (US); Gavin Thurston, Tarrytown, NY (US); Eric Jorgenson, Tarrytown, NY (US); and Aris Baras, Tarrytown, NY (US)
Assigned to Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed by Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed on Jul. 5, 2022, as Appl. No. 17/857,625.
Claims priority of provisional application 63/219,464, filed on Jul. 8, 2021.
Prior Publication US 2023/0037524 A1, Feb. 9, 2023
Int. Cl. A61K 31/506 (2006.01); A61K 31/713 (2006.01); C07K 16/28 (2006.01)

CPC A61K 31/506 (2013.01) [A61K 31/713 (2013.01); C07K 16/2896 (2013.01)]

8 Claims

1. A method of treating a subject having skin cancer, wherein the subject is heterozygous for a Carboxypeptidase Vitellogenic Like (CPVL) variant genomic nucleic acid molecule, the method comprising administering a Carboxypeptidase Vitellogenic Like (CPVL) inhibitor to the subject;

wherein the CPVL variant genomic nucleic acid molecule comprises 7:29096102:C:T, 7:28995873:G:A, 7:29030645:C:CT, 7:29096125:A:T, 7:29066109: GT:G, 7:29064221:T:TG, 7:29120891:A:C, 7:29071905:C:CT, 7:29071905:C:G, 7:29064060:C:T, 7:29064167:AC: A, 7:29086513: T: A, 7:29064132:C:CA, 7:29066026:G:T, 7:28995813:G:A, 7:29092703:C:T, 7:29195076:C:T, 7:29120892:C:A, 7:29066070:G:A, 7:29064236:T:C, 7:29095143:C:T, 7:29095143: CT:C, 7:29071879: AG:A, 7:29064077: AT: A, 7:29064100:TG:T, 7:29030600:GGA:G, 7:29066069:TG:T, 7:29064120:G:A, 7:28995858:TA:T, 7:29096218:C:T, 7:29120903: CT:C, 7:29112720:C:T, 7:29195076:C:A, 7:29030581: TGGAA:T, 7:29096219:T:C, 7:29096142:CAA:C, 7:29071905:C:T, 7:29121003: CAG:C, 7:29096102:C:G, 7:29064120:G:GC, 7:29071772:C:A, 7:29120995:GC: G, 7:29066060:G:GT, 7:29030645:CT:C, 7:29064060:C:A, 7:29066032:CA:C, 7:29112740:G:T, 7:29120989:G:GA, 7:29112702:A:G, 7:29030604:GT:G, 7:29064150:TAA:T, 7:29064087: A:AG, 7:29064093: GC:G, 7:29112740:G:C, 7:29064060:CCTTAT:C, 7:28995830; GCT:G, 7:29064221: TG:T, 7:29086483:C:T, 7:29030760:C:CTGAAA, 7:29096207:T:TCTGG, 7:29066114:TC:T, 7:29072425:T:A, 7:29112817:C:A, 7:29064115:TTC:T, 7:29086488:C:T, 7:29095087:A:T, 7:28995863:C:T, 7:29092645:C:A, 7:29096130:G:A, 7:29112766:C:T, 7:29112757:T:C, 7:29096177:C:T, 7:28995863:C:A, 7:29066115:C:A, 7:29030726:C:T, 7:29030584: A:T, 7:29072407:T:C, 7:29064135:C:G, 7:29030749:T:C, 7:29095089: T:G, 7:29030710:G:C, 7:28995876:T: A, 7:29066063: A:T, 7:29064068: T:A, 7:29112774:C:T, 7:29071894:C:T, 7:29096198:G:A, 7:29112810:C:T, 7:29120923:G:C, 7:29086539:T:C, 7:29072410:T:C 7:29120922:G:C, 7:28995851:G:C, 7:29030642:A:T, 7:29096199:G:C, 7:29096169:C:T, 7:29030738:G:C, 7:29064134: A:G, 7:29064173: A:G, 7:28995809: A:C, 7:29096199:G:A, 7:29096150:C:A, 7:29030599:C:T, 7:29072321:C:T, 7:29030737: A:C, 7:29030578:T:C, 7:29096172:G:A, 7:29092663: A:G, 7:29030682:C:A, 7:29095097:T:C, 7:29086497:T:G, 7:29092632:T:A, 7:29030611:G:A, 7:28995872:C:T, 7:28995816:T:G, 7:29092666:C:T, 7:29066097:C:T, 7:28995859: A:T, 7:29086486:C:G, 7:29086549:C:T, 7:29072416:G:A, 7:29096136:G:C, 7:29095103: A:G, 7:29092638:G:A, 7:29092660:C:T, 7:29066058:C.G, 7:29072329:A:G, 7:29030727:G:C, 7:29095088:T:A, 7:29064125:T:C, 7:29086515:T.C, 7:29064122: A:G, 7:29064090: A:G, 7:29096171:G:A, 7:29086548:G:T, 7:28995873:G:C, 7:29066117:A:G, 7:29064101:G:A, 7:29030740:T:C, 7:29095089: T:C, 7:29064164:C:T, 7:29071803:G:C, 7:29064168:C:T, 7:28995864:C:T, 7:29096144: A:G, 7:29096172:G:T, 7:29071780:G:C, 7:29112725:G:T, 7:29092680:G:A, 7:29066071:G:C, 7:29096184:G:C 7:29096112:T: A, 7:29072423: A:G, 7:29030722:G:A, 7:29064098: A:C, 7:28995852:G:A, 7:28995846:C:T, 7:29030609:C:A, 7:29112754:C:T, 7:29092683: A:C, 7:29112732:T:C, 7:29096139:C:T, 7:29096136:G:A, 7:29112719:C:A, 7:29072347:T:G, 7:29086548:G:A, 7:29064092:G:T, 7:29112750:T:C, 7:29112735:C:G, 7:29096121:C:A, 7:28995814: A:T, 7:29066108: A:G, 7:29092693:C:T, 7:29096169:C:G, 7:29095101:G:A, 7:29064212:T:C, 7:29120929:G: A, 7:29030705:G: A, 7:29095086:G:T, 7:28995812:C:T, 7:29096143: A:C, 7:29030577:C:G, 7:28995822:T:C, 7:29096174:C:G, 7:29072380: T:C, 7:29066105: A:G, 7:29064213: A:T, 7:29096138:T:C, 7:29064174:T:C, 7:29086498: A:G, 7:29064152: A:G, 7:29096159:G: A, 7:29096160: A:G, 7:29030750: A:G, 7:29071781:C:T, 7:29072339:C:T, 7:29030600:G:A, and/or 7:29096120:A:G; and

wherein the CPVL inhibitor comprises:

i) an inhibitory nucleic acid molecule that hybridizes to a CPVL nucleic acid molecule;

ii) hydroxymethyl(N-methyliminodiacetic acid)boronate (hydroxymethyl(MIDA)boronate), azidomethyl(N-methyliminodiacetic acid)boronate (azidomethyl(MIDA)boronate), or an α-functionalized alkyl(MIDA)boronate compound;

iii) a compound selected from the group consisting of

iv) an immune checkpoint inhibitor.