IP Library › Granted Patent US 12,365,896
Granted Patent B2
US 12,365,896 · App. 17/721,530 · Granted Jul 22, 2025

Complement component C3 iRNA compositions and methods of use thereof

Inventors: Mark Keating (Weston, MA); James D. McIninch (Burlington, MA); Elane Fishilevich (Rochester, MA); Kristina Yucius (Burlington, MA); Sarah Solomon (Cambridge, MA); Mark K. Schlegel (Boston, MA); Adam Castoreno (Framingham, MA); Charalambos Kaittanis (Cambridge, MA)
Assignee: Alnylam Pharmaceuticals, Inc.
C12N15/113C12N15/66C12N2310/3125C12N2310/315C12N2310/321
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,365,896
App. No.
17/721,530
Granted
Jul 22, 2025
Kind
B2
Abstract

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the complement component C3 gene (C3). The invention also relates to methods of using such RNAi agents to inhibit expression of a C3 gene and to methods of preventing and treating a C3-associated disorder, e.g., cold agglutinin disease (CAD), warm autoimmune hemolytic anemia, and paroxysmal nocturnal hemoglobinuria (PNH), lupis nephritis (LN), bullous pemphigoid, Pemphigus, e.g., Pemphigus vulgaris (PV) and Pemphigus foliaceus (PF), and C3 glomerulopathy.

Claims (64)

1. A method of inhibiting expression of a complement component C3 gene in a cell, the method comprising contacting the cell with a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of complement component C3 in a cell, or a pharmaceutically acceptable salt thereof,

wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, comprises a sense strand differing by no more than 4 bases from the nucleotide sequence 5′-gsasgccgUfuCfUfCfuacaauuacu-3′ of SEQ ID NO:4188 and an antisense strand differing by no more than 4 bases from the nucleotide sequence 5′-asGfsuaaUfuGfUfagagAfaCfggcucsgsg-3′ of SEQ ID NO:4367,

wherein a, g, c and u are 2′-O-methyl (2′-OMe) A, G, C, and U, respectively; Af, Gf, Cf, and Uf are 2′-fluoro A, G, C and U, respectively; and s is a phosphorothioate linkage,

thereby inhibiting expression of the complement component C3 gene in the cell.

2. The method of claim 1 , wherein the cell is within a subject.

3. The method of claim 2 , wherein the subject is a human.

4. The method of claim 1 , wherein contacting the cell with the dsRNA agent, or a pharmaceutically acceptable salt thereof, inhibits the expression of complement component C3 by at least 50%, 60%, 70%, 80%, 90%, or 95%.

5. The method of claim 1 , wherein inhibiting expression of complement component C3 decreases complement component C3 protein level in serum of the subject by at least 50%, 60%, 70%, 80%, 90%, or 95%.

6. The method of claim 1 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, comprises a sense strand differing by no more than 3 bases from the nucleotide sequence 5′-gsasgccgUfuCfUfCfuacaauuacu-3′ of SEQ ID NO:4188 and an antisense strand differing by no more than 3 bases from the nucleotide sequence 5′-asGfsuaaUfuGfUfagagAfaCfggcucsgsg-3′ of SEQ ID NO:4367.

7. The method of claim 1 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, comprises a sense strand differing by no more than 2 bases from the nucleotide sequence 5′-gsasgccgUfuCfUfCfuacaauuacu-3′ of SEQ ID NO:4188 and an antisense strand differing by no more than 2 bases from the nucleotide sequence 5′-asGfsuaaUfuGfUfagagAfaCfggcucsgsg-3′ of SEQ ID NO:4367.

8. The method of claim 1 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, comprises a sense strand differing by no more than 1 base from the nucleotide sequence 5′-gsasgccgUfuCfUfCfuacaauuacu-3′ of SEQ ID NO:4188 and an antisense strand differing by no more than 1 base from the nucleotide sequence 5′-asGfsuaaUfuGfUfagagAfaCfggcucsgsg-3′ of SEQ ID NO:4367.

9. The method of claim 1 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, comprises a sense strand comprising the nucleotide sequence 5′-gsasgccgUfuCfUfCfuacaauuacu-3′ of SEQ ID NO:4188 and an antisense strand comprising the nucleotide sequence 5′-asGfsuaaUfuGfUfagagAfaCfggcucsgsg-3′ of SEQ ID NO: 4367.

10. The method of claim 1 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, comprises a sense strand consisting of the nucleotide sequence 5′-gsasgccgUfuCfUfCfuacaauuacu-3′ of SEQ ID NO:4188 and an antisense strand consisting of the nucleotide sequence 5′-asGfsuaaUfuGfUfagagAfaCfggcucsgsg-3′ of SEQ ID NO: 4367.

11. The method of claim 1 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, further comprises a ligand.

12. The method of claim 11 , wherein the ligand is conjugated to the 3′ end of the sense strand of the dsRNA agent, or a pharmaceutically acceptable salt thereof.

13. The method of claim 11 , wherein the ligand is an N-acetylgalactosamine (GalNAc) derivative.

14. The method of claim 13 , wherein the ligand is one or more GalNAc derivatives attached through a monovalent, bivalent, or trivalent linker.

15. The method of claim 14 , wherein the ligand is

16. The method of claim 15 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, is conjugated to the ligand as shown in the following schematic

wherein X is O or S.

17. The method of claim 16 , wherein X is O.

18. The method of claim 1 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, is present in a pharmaceutical composition.

19. A method of treating a subject having a complement component C3-associated disorder selected from the group consisting of cold agglutinin disease (CAD), warm autoimmune hemolytic anemia, and paroxysmal nocturnal hemoglobinuria (PNH), lupus nephritis (LN), bullous pemphigoid, Pemphigus, Pemphigus vulgaris (PV), Pemphigus foliaceus (PF), and C3 glomerulopathy, comprising administering to the subject a therapeutically effective amount of a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of complement component C3 in a cell, or a pharmaceutically acceptable salt thereof,

wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, comprises a sense strand differing by no more than 4 bases from the nucleotide sequence 5′-gsasgccgUfuCfUfCfuacaauuacu-3′ of SEQ ID NO:4188 and an antisense strand differing by no more than 4 bases from the nucleotide sequence 5′-asGfsuaaUfuGfUfagagAfaCfggcucsgsg-3′ of SEQ ID NO:4367,

wherein a, g, c and u are 2′-O-methyl (2′-OMe) A, G, C, and U, respectively; Af, Gf, Cf, and Uf are 2′-fluoro A, G, C and U, respectively; and s is a phosphorothioate linkage,

thereby treating the subject having the complement component C3-associated disorder.

20. The method of claim 19 , wherein the complement component C3-associated disorder is cold agglutinin disease (CAD).

21. The method of claim 19 , wherein the subject is human.

22. The method of claim 19 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, is administered to the subject subcutaneously.

23. The method of claim 19 , further comprising administering to the subject an additional therapeutic agent for treatment of hemolysis.

24. The method of claim 19 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, comprises a sense strand differing by no more than 3 bases from the nucleotide sequence 5′-gsasgccgUfuCfUfCfuacaauuacu-3′ of SEQ ID NO:4188 and an antisense strand differing by no more than 3 bases from the nucleotide sequence 5′-asGfsuaaUfuGfUfagagAfaCfggcucsgsg-3′ of SEQ ID NO:4367.

25. The method of claim 19 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, comprises a sense strand differing by no more than 2 bases from the nucleotide sequence 5′-gsasgccgUfuCfUfCfuacaauuacu-3′ of SEQ ID NO:4188 and an antisense strand differing by no more than 2 bases from the nucleotide sequence 5′-asGfsuaaUfuGfUfagagAfaCfggcucsgsg-3′ of SEQ ID NO:4367.

26. The method of claim 19 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, comprises a sense strand differing by no more than 1 base from the nucleotide sequence 5′-gsasgccgUfuCfUfCfuacaauuacu-3′ of SEQ ID NO:4188 and an antisense strand differing by no more than 1 base from the nucleotide sequence 5′-asGfsuaaUfuGfUfagagAfaCfggcucsgsg-3′ of SEQ ID NO:4367.

27. The method of claim 19 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, comprises a sense strand comprising the nucleotide sequence 5′-gsasgccgUfuCfUfCfuacaauuacu-3′ of SEQ ID NO:4188 and an antisense strand comprising the nucleotide sequence 5′-asGfsuaaUfuGfUfagagAfaCfggcucsgsg-3′ of SEQ ID NO: 4367.

28. The method of claim 19 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, comprises a sense strand consisting of the nucleotide sequence 5′-gsasgccgUfuCfUfCfuacaauuacu-3′ of SEQ ID NO:4188 and an antisense strand consisting of the nucleotide sequence 5′-asGfsuaaUfuGfUfagagAfaCfggcucsgsg-3′ of SEQ ID NO: 4367.

29. The method of claim 19 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, further comprises a ligand.

30. The method of claim 29 , wherein the ligand is conjugated to the 3′ end of the sense strand of the dsRNA agent, or a pharmaceutically acceptable salt thereof.

31. The method of claim 29 , wherein the ligand is an N-acetylgalactosamine (GalNAc) derivative.

32. The method of claim 31 , wherein the ligand is one or more GalNAc derivatives attached through a monovalent, bivalent, or trivalent linker.

33. The method of claim 32 , wherein the ligand is

34. The method of claim 33 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, is conjugated to the ligand as shown in the following schematic

wherein X is O or S.

35. The method of claim 34 , wherein X is O.

36. The method of claim 19 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, is present in a pharmaceutical composition.

37. A method of treating a subject having a complement component C3-associated disorder selected from the group consisting of cold agglutinin disease (CAD), warm autoimmune hemolytic anemia, and paroxysmal nocturnal hemoglobinuria (PNH), lupus nephritis (LN), bullous pemphigoid, Pemphigus, Pemphigus vulgaris (PV), Pemphigus foliaceus (PF), and C3 glomerulopathy, comprising administering to the subject a therapeutically effective amount of a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of complement component C3 in a cell, or a pharmaceutically acceptable salt thereof, comprising a sense strand consisting of the nucleotide sequence 5′-gsasgccgUfuCfUfCfuacaauuacu-3′ of SEQ ID NO:4188 and an antisense strand comprising the nucleotide sequence 5′-asGfsuaaUfuGfUfagagAfaCfggcucsgsg-3′ of SEQ ID NO:4367, wherein a, g, c and u are 2′-O-methyl (2′-OMe) A, G, C, and U, respectively; Af, Gf, Cf, and Uf are 2′-fluoro A, G, C and U, respectively; and s is a phosphorothioate linkage,

wherein the 3′-end of the sense strand of the dsRNA agent, or a pharmaceutically acceptable salt thereof, is conjugated to a ligand as shown in the following schematic

wherein X is O, thereby treating the subject having the complement component C3-associated disorder.

38. The method of claim 37 , wherein the complement component C3-associated disorder is cold agglutinin disease (CAD).

39. The method of claim 37 , wherein the subject is human.

40. The method of claim 37 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, is administered to the subject subcutaneously.

41. The method of claim 37 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, is present in a pharmaceutical composition.

42. A method of treating a subject having a complement component C3-associated disorder selected from the group consisting of cold agglutinin disease (CAD), warm autoimmune hemolytic anemia, and paroxysmal nocturnal hemoglobinuria (PNH), lupus nephritis (LN), bullous pemphigoid, Pemphigus, Pemphigus vulgaris (PV), Pemphigus foliaceus (PF), and C3 glomerulopathy, comprising administering to the subject a therapeutically effective amount of a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of complement component C3 in a cell, or a pharmaceutically acceptable salt thereof, consisting of a sense strand consisting of the nucleotide sequence 5′-gsasgccgUfuCfUfCfuacaauuacu-3′ of SEQ ID NO:4188 and an antisense strand consisting of the nucleotide sequence 5′-asGfsuaaUfuGfUfagagAfaCfggcucsgsg-3′ of SEQ ID NO:4367, wherein a, g, c and u are 2′-O-methyl (2′-OMe) A, G, C, and U, respectively; Af, Gf, Cf, and Uf are 2′-fluoro A, G, C and U, respectively; and s is a phosphorothioate linkage,

wherein the 3′-end of the sense strand of the dsRNA agent, or a pharmaceutically acceptable salt thereof, is conjugated to a ligand as shown in the following schematic

wherein X is O, thereby treating the subject having the complement component C3-associated disorder.

43. The method of claim 42 , wherein the complement component C3-associated disorder is cold agglutinin disease (CAD).

44. The method of claim 42 , wherein the subject is human.

45. The method of claim 42 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, is administered to the subject subcutaneously.

46. The method of claim 42 , wherein the dsRNA agent, or a pharmaceutically acceptable salt thereof, is present in a pharmaceutical composition.

47. The method of claim 19 , wherein the dsRNA agent is in a salt form.

48. The method of claim 47 , wherein the dsRNA agent is in a sodium salt form.

49. The method of claim 37 , wherein the dsRNA agent is in a salt form.

50. The method of claim 49 , wherein the dsRNA agent is in a sodium salt form.

51. The method of claim 42 , wherein the dsRNA agent is in a salt form.

52. The method of claim 51 , wherein the dsRNA agent is in a sodium salt form.

Assignments (2)
SECURITY INTEREST Recorded Oct 1, 2025
From: ALNYLAM PHARMACEUTICALS, INC.; SIRNA THERAPEUTICS, INC.
To: BANK OF AMERICA, N.A.
Reel/Frame 072996/0337 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 3, 2022
From: KEATING, MARK; MCININCH, JAMES D.; FISHILEVICH, ELANE; YUCIUS, KRISTINA; SOLOMON, SARAH; SCHLEGEL, MARK K.; CASTORENO, ADAM; KAITTANIS, CHARALAMBOS
To: ALNYLAM PHARMACEUTICALS, INC.
Reel/Frame 059797/0402 →
Continuity (3)
Continuation PCTUS2020056563 · Oct 21, 2020
Provisional Application 62924210 · Oct 22, 2019
Related Publication 20220364088A1 · Nov 17, 2022
References Cited (82)
US 10465194B2 · Borodovsky et al. · 2019 [cited by applicant]
US 11186842B2 · Borodovsky et al. · 2021 [cited by applicant]
US 20030096775A1 · Graham et al. · 2003 [cited by applicant]
US 20070088154A1 · Khvorova et al. · 2007 [cited by applicant]
US 20070123484A1 · Bhat · 2007 [cited by applicant]
US 20080113351A1 · Naito et al. · 2008 [cited by applicant]
US 20090239814A1 · Manoharan et al. · 2009 [cited by applicant]
US 20090306178A1 · Bhat et al. · 2009 [cited by applicant]
US 20130217756A1 · Cancilla et al. · 2013 [cited by applicant]
US 20130281511A1 · Bettencourt et al. · 2013 [cited by applicant]
US 20160222389A1 · Grossman · 2016 [cited by applicant]
US 20170159055A1 · Prakash et al. · 2017 [cited by applicant]
US 20200263183A1 · Borodovsky et al. · 2020 [cited by applicant]
US 20200339998A1 · Borodovsky et al. · 2020 [cited by applicant]
US 20220364088A1 · Keating et al. · 2022 [cited by applicant]
US 20230257749A1 · McIninch et al. · 2023 [cited by applicant]
US 20230272382A1 · Keating et al. · 2023 [cited by applicant]
US 20240018515A1 · McIninch et al. · 2024 [cited by applicant]
US 20240209369A1 · Keating et al. · 2024 [cited by applicant]
EP 1752536A1 · 2007 [cited by applicant]
WO WO2003066805A2 · 2003 [cited by applicant]
WO WO2006047673A2 · 2006 [cited by applicant]
WO WO2007064846A2 · 2007 [cited by applicant]
WO WO2007089375A2 · 2007 [cited by applicant]
WO WO2008036841A2 · 2008 [cited by applicant]
WO WO2010048352A2 · 2010 [cited by applicant]
WO WO2012037254A1 · 2012 [cited by applicant]
WO WO2013067076A2 · 2013 [cited by applicant]
WO WO2013074974A2 · 2013 [cited by applicant]
WO WO2014107763A1 · 2014 [cited by applicant]
WO WO2015038939A2 · 2015 [cited by applicant]
WO WO2015089368A2 · 2015 [cited by applicant]
WO WO2015168635A2 · 2015 [cited by applicant]
WO WO2017040078A1 · 2017 [cited by applicant]
WO WO2018075373A1 · 2018 [cited by applicant]
WO WO2019027015A1 · 2019 [cited by applicant]
WO WO2019089922A1 · 2019 [cited by applicant]
WO WO2020104669A1 · 2020 [cited by applicant]
WO WO2021081026A1 · 2021 [cited by applicant]
WO WO2021178607A1 · 2021 [cited by applicant]
WO WO2021222549A1 · 2021 [cited by applicant]
WO WO2023044370A2 · 2023 [cited by applicant]
WO WO2023076451A1 · 2023 [cited by applicant]
Bode et al. (“Complement component C3 as a new target to lower albuminuria in hypertensive kidney disease.” British Journal of Pharmacology 180.18 (2023): 2412-2435. [cited by examiner]
Zelek et al. (“Targeting complement in neurodegeneration: challenges, risks, and strategies.” Trends in Pharmacological Sciences 43.8 (2022): 615-628). [cited by examiner]
Smith, Richard JH, et al. (“C3 glomerulopathy—understanding a rare complement-driven renal disease.” Nature reviews nephrology 15.3 (2019): 129-143). [cited by examiner]
Li, Nicholas L. et al. (“Expanding the role of complement therapies: the case for lupus nephritis.” Journal of Clinical Medicine 10.4 (2021): 626). [cited by examiner]
Lindorfer et al. (Blood, Mar. 18, 2010 vol. 115, No. 11 2283-2291). [cited by examiner]
U.S. Appl. No. 15/176,231 U.S. Pat. No. 10,465,194, filed Jun. 8, 2016 Nov. 5, 2018, US 20160298124, Granted. [cited by applicant]
U.S. Appl. No. 16/574,158 U.S. Pat. No. 11,186,842, filed Sep. 18, 2019 Nov. 30, 2021, US 20200263183, Granted. [cited by applicant]
U.S. Appl. No. 16/925,463, filed Jul. 10, 2020, US 20200339998, Abandoned. [cited by applicant]
U.S. Appl. No. 17/405,199, filed Aug. 18, 2021, US 20220213486, Abandoned. [cited by applicant]
U.S. Appl. No. 18/405,281, filed Jan. 5, 2024, N/A, Pending. [cited by applicant]
PCT/US2014/069951, Dec. 12, 2014, WO 2015/089368, Completed. [cited by applicant]
U.S. Appl. No. 16/760,593 U.S. Pat. No. 11,866,701, filed Apr. 30, 2020 Jan. 9, 2024, US 20210261959, Granted. [cited by applicant]
U.S. Appl. No. 18/519,295, filed Nov. 27, 2023, N/A, Pending. [cited by applicant]
PCT/US2018/058705, Nov. 1, 2018, WO 2019/089922, Completed. [cited by applicant]
U.S. Appl. No. 18/594,132, filed Mar. 4, 2024, US 20240209369, Published. [cited by applicant]
PCT/US2020/056563, Oct. 21, 2020, WO 2021/081026, Completed. [cited by applicant]
U.S. Appl. No. 17/974,598, filed Oct. 27, 2022, US 20240018515, Published. [cited by applicant]
PCT/US2021/029872, Apr. 29, 2021, WO 2021/222549, Completed. [cited by applicant]
U.S. Appl. No. 17/900,919, filed Sep. 1, 2022, US 20230272382, Published. [cited by applicant]
PCT/US2021/020777, Mar. 4, 2021, WO 2021/178607, Completed. [cited by applicant]
PCT/US2022/076464, Sep. 15, 2022, WO 2023/044370, Published. [cited by applicant]
U.S. Appl. No. 18/187,741 U.S. Pat. No. 11,965,166, filed Mar. 22, 2023 Apr. 23, 2024, US 20230257749, Granted. [cited by applicant]
U.S. Appl. No. 18/598,006, filed Mar. 7, 2024, N/A, Pending. [cited by applicant]
PCT/US2022/047987, filed Oct. 27, 2022, WO 2023/076451, Completed. [cited by applicant]
Bora et al., Complement activation via alternative pathway is critical in the development of laser-induced choroidal neovascularization: role of factor B and factor H. J Immunol. Aug. 1, 2006;177(3):1872-8. [cited by applicant]
Borodovsky et al., Development of RNAi Therapeutics Targeting the Complement Pathway. Blood. 2013;122(21)2471. [cited by applicant]
Cheng et al., [Effect of C5-siRNA silencing receptor C5 on myocardial ischemia injury in rats]. Nan Fang Yi Ke Da Xue Xue Bao. Jun. 2010;30(6):1486-8. [cited by applicant]
International Search Report and Written Opinion for Application No. PCT/US2014/069951, dated Jul. 6, 2015. [cited by applicant]
Zheng et al., “Preventing Renal Ischemia-Reperfusion Injury Using Small Interfering RNA by Targeting Complement 3 Gene,” American Journal of Transplantation 2006; 6: 2099-2108. [cited by applicant]
Zheng et al., “Protection of Renal Ischemia Injury using Combination Gene Silencing of Complement 3 and Caspase 3 Genes,” [cited by applicant]
Reynolds et al., Rational siRNA design for RNA interference. Nat Biotechnol. Mar. 2004;22(3):326-30. [cited by applicant]
International Search Report and Written Opinion from PCT/US2018/058705, mailed on Mar. 1, 2019. [cited by applicant]
International Search Report and Written Opinion from PCT/US2020/056563, mailed on Mar. 22, 2021. [cited by applicant]
International Search Report and Written Opinion from PCT/US2021/020777, mailed on Aug. 16, 2021. [cited by applicant]
Vickers et al., Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent antisense agents. A comparative analysis. J Biol Chem. Feb. 28, 2003;278(9):7108-18. [cited by applicant]
Watts et al., “Gene silencing by siRNAs and antisense oligonucleotides in the laboratory and the clinic”, J Pathol 2012; 226: 365-379. [cited by applicant]
Wang et al., “Protecting neurons from cerebral ischemia/reperfusion injury via nanoparticle-mediated delivery of an siRNA to inhibit microglial neurotoxicity”, Biomaterials 161 (2018) 95-105. [cited by applicant]
Ricklin et al, “Complement component C3—The “Swiss Army Knife” of innate immunity and host defense”, Immunol Rev. Nov. 2016: 274(1): 33-58. [cited by applicant]
Riihila, et al. “Complement Component C3 and Complement Factor B Promote Growth of Cutaneous Squamous Cell Carcinoma” Am. J. Path. 187(5): 1186-1197, 2017. [cited by applicant]
Cited By (2)
US 12,680,099 US 12,703,865