IP Library › Granted Patent US 12,358,982
Granted Patent B2
US 12,358,982 · App. 17/402,325 · Granted Jul 15, 2025

Multifunctional molecules that bind to T cell related cancer cells and uses thereof

Inventors: Andreas Loew (Boston, MA); Nidhi Malhotra (Boston, MA); Madan Katragadda (Acton, MA); Seng-Lai Tan (Sudbury, MA); Jonathan Hsu (Waltham, MA); Brian Edward Vash (Cambridge, MA); Stephanie J. Maiocco (Arlington, MA); Peter Marek (Hudson, MA); Gurkan Guntas (Newton, MA)
Assignee: Marengo Therapeutics, Inc.
C07K16/28A61K39/3955A61P35/00C07K16/2809C07K16/2827A61K2039/505C07K2317/31C07K2317/52C07K2317/55C07K2317/56C07K2317/565C07K2317/622C07K2317/732C07K2317/92
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Quick Facts
Patent No.
US 12,358,982
App. No.
17/402,325
Granted
Jul 15, 2025
Kind
B2
Abstract

Multifunctional molecules that include i) an antigen binding domain that binds to a T cell receptor beta chain constant domain 1 or T cell receptor beta chain constant domain 2; and one, two or all of: (ii) an immune cell engager (e.g., chosen from an NK cell engager, a T cell engager, a B cell engager, a dendritic cell engager, or a macrophage cell engager); (iii) a cytokine molecule or cytokine inhibitor molecule; (iv) a death receptor signal enhancer; and/or (v) a stromal modifying moiety are disclosed. Additionally disclosed are nucleic acids encoding the same, methods of producing the aforesaid molecules, and methods of treating a cancer using the aforesaid molecules.

Claims (110)

1. A multifunctional molecule, comprising:

(a) a first antigen binding domain that selectively binds to T cell receptor beta chain constant domain 1 (TRBC1); wherein the first antigen binding domain comprises:

(i) a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (VHCDR1), a heavy chain complementarity determining region 2 (VHCDR2), and a heavy chain complementarity determining region 3 (VHCDR3) of SEQ ID NO: 7346, SEQ ID NO: 7355, and SEQ ID NO: 202, respectively; and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (VLCDR1), a light chain complementarity determining region 2 (VLCDR2), and a light chain complementarity determining region 3 (VLCDR3) of: SEQ ID NO: 223, SEQ ID NO: 224, and SEQ ID NO: 225, respectively;

(ii) a VH comprising a VHCDR1, a VHCDR2, and a VHCDR3 of SEQ ID NO: 200, SEQ ID NO: 7355, and SEQ ID NO: 202, respectively; and a VL comprising a VLCDR1, a VLCDR2, and a VLCDR3 of SEQ ID NO: 223, SEQ ID NO: 224, and SEQ ID NO: 225, respectively;

(iii) a VH comprising a VHCDR1, a VHCDR2, and a VHCDR3 of SEQ ID NO: 200, SEQ ID NO: 201, and SEQ ID NO: 202, respectively; and a VL comprising a VLCDR1, a VLCDR2, and a VLCDR3 of SEQ ID NO: 223, SEQ ID NO: 224, and SEQ ID NO: 225, respectively;

(iv) a VH comprising a VHCDR1, a VHCDR2, and a VHCDR3 of SEQ ID NO: 7346, SEQ ID NO: 201, and SEQ ID NO: 202, respectively; and a VL comprising a VLCDR1, a VLCDR2, and a VLCDR3 of SEQ ID NO: 223, SEQ ID NO: 224, and SEQ ID NO: 225, respectively;

(v) a VH comprising a VHCDR1, a VHCDR2, and a VHCDR3 of SEQ ID NO: 7354, SEQ ID NO: 201, and SEQ ID NO: 202, respectively; and a VL comprising a VLCDR1, a VLCDR2, and a VLCDR3 of SEQ ID NO: 7367, SEQ ID NO: 224, and SEQ ID NO: 225, respectively;

(vi) a VH comprising a VHCDR1, a VHCDR2, and a VHCDR3 of SEQ ID NO: 7346, SEQ ID NO: 7355, and SEQ ID NO: 202, respectively; and a VL comprising a VLCDR1, a VLCDR2, and a VLCDR3 of SEQ ID NO: 223, SEQ ID NO: 7368, and SEQ ID NO: 225, respectively; or

(vii) a VH comprising a VHCDR1, a VHCDR2, and a VHCDR3 of SEQ ID NO: 7354, SEQ ID NO: 7355, and SEQ ID NO: 202, respectively; and a VL comprising a VLCDR1, a VLCDR2, and a VLCDR3 of SEQ ID NO: 7367, SEQ ID NO: 7368, and SEQ ID NO: 739, respectively; and

(b) a second antigen binding domain that selectively binds to NKp30; wherein the second antigen binding domain comprises:

(i) a VH comprising a VHCDR1, a VHCDR2, and a VHCDR3 of SEQ ID NO: 7313, SEQ ID NO: 6001, and SEQ ID NO: 7315, respectively; and a VL comprising a VLCDR1, a VLCDR2, and a VLCDR3 of SEQ ID NO: 7326, SEQ ID NO: 7327, and SEQ ID NO: 7329, respectively;

(ii) a VH comprising a VHCDR1, a VHCDR2, and a VHCDR3 of SEQ ID NO: 7313, SEQ ID NO: 6001, and SEQ ID NO: 6002, respectively; and a VL comprising a VLCDR1, a VLCDR2, and a VLCDR3 of SEQ ID NO: 7326, SEQ ID NO: 7327, and SEQ ID NO: 7329, respectively;

(iii) a VH comprising a VHCDR1, a VHCDR2, and a VHCDR3 of SEQ ID NO: 7313, SEQ ID NO: 6001, and SEQ ID NO: 6002, respectively; and a VL comprising a VLCDR1, a VLCDR2, and a VLCDR3 of SEQ ID NO: 6063, SEQ ID NO: 6064, and SEQ ID NO: 7293, respectively;

(iv) a VH comprising a VHCDR1, a VHCDR2, and a VHCDR3 of SEQ ID NO: 7313, SEQ ID NO: 6008, and SEQ ID NO: 6009, respectively; and a VL comprising a VLCDR1, a VLCDR2, and a VLCDR3 of SEQ ID NO: 6070, SEQ ID NO: 6071, and SEQ ID NO: 6072, respectively;

(v) a VH comprising a VHCDR1, a VHCDR2, and a VHCDR3 of SEQ ID NO: 7313, SEQ ID NO: 7385, and SEQ ID NO: 7315, respectively; and a VL comprising a VLCDR1, a VLCDR2, and a VLCDR3 of SEQ ID NO: 6070, SEQ ID NO: 6064, and SEQ ID NO: 7321, respectively; or

(vi) a VH comprising a VHCDR1, a VHCDR2, and a VHCDR3 of SEQ ID NO: 7313, SEQ ID NO: 7318, and SEQ ID NO: 6009, respectively; and a VL comprising a VLCDR1, a VLCDR2, and a VLCDR3 of SEQ ID NO: 6070, SEQ ID NO: 6064, and SEQ ID NO: 7321, respectively.

2. The multifunctional molecule of claim 1 , wherein the first antigen binding domain comprises:

(a) the VH comprising

(i) the VHCDR1 amino acid sequence of SEQ ID NO: 7346,

(ii) the VHCDR2 amino acid sequence of SEQ ID NO: 7355 or SEQ ID NO: 201, and

(iii) the VHCDR3 amino acid sequence of SEQ ID NO: 202; and

(b) the VL comprising

(i) the VLCDR1 amino acid sequence of SEQ ID NO: 223,

(ii) the VLCDR2 amino acid sequence of SEQ ID NO: 224, and

(iii) the VLCDR3 amino acid sequence of SEQ ID NO: 225.

3. The multifunctional molecule of claim 2 , wherein the first antigen binding domain comprises:

(a) the VH comprising:

(i) a heavy chain framework region 1 (VHFWR1) amino acid sequence with at least 90% sequence identity to SEQ ID NO: 203,

(ii) a VHFWR2 amino acid sequence with at least 90% sequence identity to SEQ ID NO: 204,

(iii) a VHFWR3 amino acid sequence with at least 90% sequence identity to SEQ ID NO: 205, and

(iv) a VHFWR4 amino acid sequence with at least 90% sequence identity to SEQ ID NO: 206; and/or

(b) the VL comprising:

(i) a light chain framework region 1 (VLFWR1) amino acid sequence with at least 90% sequence identity to SEQ ID NO: 226,

(ii) a VLFWR2 amino acid sequence with at least 90% sequence identity to SEQ ID NO: 227,

(iii) a VLFWR3 amino acid sequence with at least 90% sequence identity to SEQ ID NO: 228, and

(iv) a VLFWR4 amino acid sequence with at least 90% sequence identity to SEQ ID NO: 229.

4. The multifunctional molecule of claim 1 , wherein the first antigen binding domain comprises:

(a) the VH comprising an amino acid sequence with at least 75% sequence identity to any one of SEQ ID NOs: 250-254, 7343, 7344, and 7350-7352; and

(b) the VL comprising an amino acid sequence with at least 75% sequence identity to any one of SEQ ID NOs: 255-260 and 7357-7360.

5. The multifunctional molecule of claim 2 , wherein the first antigen binding domain comprises:

(a) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7351 or SEQ ID NO: 253; and

(b) the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 258.

6. The multifunctional molecule of claim 1 , wherein the first antigen binding domain comprises:

(a) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7351 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 258;

(b) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 250 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 255;

(c) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 251 and a VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 256;

(d) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 252 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 257;

(e) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 253 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 258;

(f) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 254 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 259;

(g) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7343 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 260;

(h) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7344 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7357;

(i) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7350 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7358;

(j) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7351 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7359; or

(k) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7352 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO:7360.

7. The multifunctional molecule of claim 1 , wherein the first antigen binding domain comprises:

(a) a heavy chain comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7382 or SEQ ID NO: 7379;

(b) a light chain comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NOs: 7380; or

(c) any combination thereof.

8. The multifunctional molecule of claim 1 , wherein the first antigen binding domain has a higher affinity for a T cell receptor comprising TRBC1 than for a T cell receptor comprising TRBC2.

9. The multifunctional molecule of claim 1 , wherein the second antigen binding domain comprises:

(a) the VH comprising:

(i) the VHCDR1 amino acid sequence of SEQ ID NO: 7313,

(ii) the VHCDR2 amino acid sequence of SEQ ID NO: 6001, and

(iii) the VHCDR3 amino acid sequence of SEQ ID NO: 7315; and

(b) the VL comprising:

(i) the VLCDR1 amino acid sequence of SEQ ID NO: 7326,

(ii) the VLCDR2 amino acid sequence of SEQ ID NO: 7327, and

(iii) the VLCDR3 amino acid sequence of SEQ ID NO: 7329.

10. The multifunctional molecule of claim 1 , wherein the second antigen binding domain comprises:

(a) the VH comprising an amino acid sequence with at least 75% sequence identity to any one of SEQ ID NOs: 6121-6134, 7295, 7297, 7298, and 7300-7304; and

(b) the VL comprising an amino acid sequence with at least 75% sequence identity to any one of SEQ ID NOs: 6136-6147, 7294, 7296, 7299, and 7305-7309.

11. The multifunctional molecule of claim 9 , wherein the second antigen binding domain comprises:

(a) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7302; and

(b) the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7309.

12. The multifunctional molecule of claim 4 , wherein the second antigen binding domain comprises:

(a) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7302 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7309;

(b) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6121 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7294;

(c) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6122 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6136;

(d) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6123 and the a VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6137;

(e) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6124 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6138;

(f) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6125 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6139;

(g) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6126 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6140;

(h) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6127 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6141;

(i) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6129 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6142;

(j) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6130 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6143;

(k) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6131 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6144;

(l) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6132 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6145;

(m) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6133 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6146;

(n) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6134 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 6147;

(o) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7295 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7296;

(p) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7298 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7299;

(q) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7300 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7305;

(r) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7301 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7306;

(s) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7302 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7307;

(t) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7303 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7308; or

(u) the VH comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7304 and the VL comprising an amino acid sequence with at least 75% sequence identity to SEQ ID NO: 7309.

13. The multifunctional molecule of claim 1 , wherein the second antigen binding domain comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 7383.

14. The multifunctional molecule of claim 1 , wherein the multifunctional molecule further comprises a cytokine molecule.

15. The multifunctional molecule of claim 14 , wherein the cytokine molecule is interleukin-2 (IL-2), interleukin-7 (IL-7), interleukin-12 (IL-12), interleukin-15 (IL-15), interleukin-18 (IL-18), interleukin-21 (IL-21), or interferon gamma.

16. The multifunctional molecule of claim 1 , wherein the multifunctional molecule further comprises a TGF-beta inhibitor.

17. The multifunctional molecule of claim 16 , wherein the TGF-beta inhibitor comprises the extracellular domain of a TGF-beta receptor.

18. The multifunctional molecule of claim 1 , comprising:

(a) the first antigen binding domain that comprises the VH and the VL of claim 2 ,

(b) the second antigen binding domain that comprises the VH and the VL of claim 9 , and

(c) a cytokine molecule that is IL-2.

19. The multifunctional molecule of claim 18 , wherein the multifunctional molecule comprises an immunoglobulin constant domain.

20. A pharmaceutical composition comprising the multifunctional molecule of claim 1 ; and a pharmaceutically acceptable carrier, excipient, or stabilizer.

21. A polynucleotide comprising a sequence encoding the multifunctional molecule of claim 1 .

22. A host cell comprising the polynucleotide of claim 21 .

23. A method of making the multifunctional molecule of claim 1 , comprising culturing the host cell of claim 22 under suitable conditions for gene expression and/or homo- or heterodimerization.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 9, 2021
From: LOEW, ANDREAS; MALHOTRA, NIDHI; KATRAGADDA, MADAN; TAN, SENG-LAI; HSU, JONATHAN; VASH, BRIAN EDWARD; MAIOCCO, STEPHANIE J.; MAREK, PETER; GUNTAS, GURKAN
To: ELSTAR THERAPEUTICS, INC.
Reel/Frame 057429/0138 →
CHANGE OF NAME Recorded Sep 9, 2021
From: ELSTAR THERAPEUTICS, INC.
To: MARENGO THERAPEUTICS, INC.
Reel/Frame 057453/0803 →
Continuity (3)
Continuation PCTUS2020019291 · Feb 21, 2020
Provisional Application 62808646 · Feb 21, 2019
Related Publication 20210380682A1 · Dec 9, 2021
References Cited (400)
US 861745A · Maxwell · 1907 [cited by applicant]
US 4433059A · Chang et al. · 1984 [cited by applicant]
US 4439196A · Higuchi · 1984 [cited by applicant]
US 4444878A · Paulus · 1984 [cited by applicant]
US 4447224A · DeCant, Jr. et al. · 1984 [cited by applicant]
US 4447233A · Mayfield · 1984 [cited by applicant]
US 4475196A · La Zor · 1984 [cited by applicant]
US 4486194A · Ferrara · 1984 [cited by applicant]
US 4487603A · Harris · 1984 [cited by applicant]
US 4522811A · Eppstein et al. · 1985 [cited by applicant]
US 4596556A · Morrow et al. · 1986 [cited by applicant]
US 4676980A · Segal et al. · 1987 [cited by applicant]
US 4737456A · Weng et al. · 1988 [cited by applicant]
US 4790824A · Morrow et al. · 1988 [cited by applicant]
US 4816567A · Cabilly et al. · 1989 [cited by applicant]
US 4941880A · Burns · 1990 [cited by applicant]
US 5057423A · Hiserodt et al. · 1991 [cited by applicant]
US 5064413A · McKinnon et al. · 1991 [cited by applicant]
US 5116615A · Gokcen et al. · 1992 [cited by applicant]
US 5208020A · Chari et al. · 1993 [cited by applicant]
US 5223409A · Ladner et al. · 1993 [cited by applicant]
US 5225539A · Winter · 1993 [cited by applicant]
US 5273743A · Ahlem et al. · 1993 [cited by applicant]
US 5312335A · McKinnon et al. · 1994 [cited by applicant]
US 5374548A · Caras · 1994 [cited by applicant]
US 5383851A · McKinnon, Jr. et al. · 1995 [cited by applicant]
US 5391377A · Barnwell · 1995 [cited by applicant]
US 5399163A · Peterson et al. · 1995 [cited by applicant]
US 5399331A · Loughrey et al. · 1995 [cited by applicant]
US 5416016A · Low et al. · 1995 [cited by applicant]
US 5416064A · Chari et al. · 1995 [cited by applicant]
US 5500362A · Robinson et al. · 1996 [cited by applicant]
US 5534254A · Huston et al. · 1996 [cited by applicant]
US 5571894A · Wels et al. · 1996 [cited by applicant]
US 5582996A · Curtis · 1996 [cited by applicant]
US 5585089A · Queen et al. · 1996 [cited by applicant]
US 5587458A · King et al. · 1996 [cited by applicant]
US 5591828A · Bosslet et al. · 1997 [cited by applicant]
US 5624821A · Winter et al. · 1997 [cited by applicant]
US 5626561A · Butler et al. · 1997 [cited by applicant]
US 5635483A · Pettit et al. · 1997 [cited by applicant]
US 5635602A · Cantor et al. · 1997 [cited by applicant]
US 5637481A · Ledbetter et al. · 1997 [cited by applicant]
US 5641870A · Rinderknecht et al. · 1997 [cited by applicant]
US 5648237A · Carter · 1997 [cited by applicant]
US 5648260A · Winter et al. · 1997 [cited by applicant]
US 5693761A · Queen et al. · 1997 [cited by applicant]
US 5693762A · Queen et al. · 1997 [cited by applicant]
US 5712374A · Kuntsmann et al. · 1998 [cited by applicant]
US 5714586A · Kunstmann et al. · 1998 [cited by applicant]
US 5731116A · Matsuo et al. · 1998 [cited by applicant]
US 5731168A · Carter et al. · 1998 [cited by applicant]
US 5739116A · Hamann et al. · 1998 [cited by applicant]
US 5747036A · Brenner et al. · 1998 [cited by applicant]
US 5750373A · Garrard et al. · 1998 [cited by applicant]
US 5766947A · Rittershaus et al. · 1998 [cited by applicant]
US 5767285A · Hamann et al. · 1998 [cited by applicant]
US 5770429A · Lonberg et al. · 1998 [cited by applicant]
US 5770701A · McGahren et al. · 1998 [cited by applicant]
US 5770710A · McGahren et al. · 1998 [cited by applicant]
US 5773001A · Hamann et al. · 1998 [cited by applicant]
US 5780588A · Pettit et al. · 1998 [cited by applicant]
US 5787900A · Butler et al. · 1998 [cited by applicant]
US 5789199A · Joly et al. · 1998 [cited by applicant]
US 5811097A · Allison et al. · 1998 [cited by applicant]
US 5821337A · Carter et al. · 1998 [cited by applicant]
US 5831012A · Nilsson et al. · 1998 [cited by applicant]
US 5837242A · Holliger et al. · 1998 [cited by applicant]
US 5837821A · Wu · 1998 [cited by applicant]
US 5840523A · Simmons et al. · 1998 [cited by applicant]
US 5843069A · Butler et al. · 1998 [cited by applicant]
US 5844094A · Hudson et al. · 1998 [cited by applicant]
US 5849500A · Breitling et al. · 1998 [cited by applicant]
US 5849589A · Tedder et al. · 1998 [cited by applicant]
US 5861155A · Lin · 1999 [cited by applicant]
US 5864019A · King et al. · 1999 [cited by applicant]
US 5869046A · Presta et al. · 1999 [cited by applicant]
US 5869620A · Whitlow et al. · 1999 [cited by applicant]
US 5877296A · Hamann et al. · 1999 [cited by applicant]
US 5902745A · Butler et al. · 1999 [cited by applicant]
US 5910573A · Plueckthun et al. · 1999 [cited by applicant]
US 5913998A · Butler et al. · 1999 [cited by applicant]
US 5932448A · Tso et al. · 1999 [cited by applicant]
US 5959083A · Bosslet et al. · 1999 [cited by applicant]
US 5959177A · Hein et al. · 1999 [cited by applicant]
US 5968753A · Tseng-Law et al. · 1999 [cited by applicant]
US 5980889A · Butler et al. · 1999 [cited by applicant]
US 5989830A · Davis et al. · 1999 [cited by applicant]
US 6005079A · Casterman et al. · 1999 [cited by applicant]
US 6040498A · Stomp et al. · 2000 [cited by applicant]
US 6075181A · Kucherlapati et al. · 2000 [cited by applicant]
US 6120766A · Hale et al. · 2000 [cited by applicant]
US 6150584A · Kucherlapati et al. · 2000 [cited by applicant]
US 6171586B1 · Lam et al. · 2001 [cited by applicant]
US 6172197B1 · McCafferty et al. · 2001 [cited by applicant]
US 6194551B1 · Idusogie et al. · 2001 [cited by applicant]
US 6239259B1 · Davis et al. · 2001 [cited by applicant]
US 6248516B1 · Winter et al. · 2001 [cited by applicant]
US 6267958B1 · Andya et al. · 2001 [cited by applicant]
US 6291158B1 · Winter et al. · 2001 [cited by applicant]
US 6294353B1 · Pack et al. · 2001 [cited by applicant]
US 6333396B1 · Filpula et al. · 2001 [cited by applicant]
US 6352694B1 · June et al. · 2002 [cited by applicant]
US 6417429B1 · Hein et al. · 2002 [cited by applicant]
US 6420548B1 · Vezina et al. · 2002 [cited by applicant]
US 6476198B1 · Kang · 2002 [cited by applicant]
US 6511663B1 · King et al. · 2003 [cited by applicant]
US 6534055B1 · June et al. · 2003 [cited by applicant]
US 6582915B1 · Griffiths et al. · 2003 [cited by applicant]
US 6593081B1 · Griffiths et al. · 2003 [cited by applicant]
US 6602684B1 · Umana et al. · 2003 [cited by applicant]
US 6630579B2 · Chari et al. · 2003 [cited by applicant]
US 6632427B1 · Finiels et al. · 2003 [cited by applicant]
US 6670453B2 · Frenken et al. · 2003 [cited by applicant]
US 6696245B2 · Winter et al. · 2004 [cited by applicant]
US 6703199B1 · Koide · 2004 [cited by applicant]
US 6737056B1 · Presta · 2004 [cited by applicant]
US 6743896B2 · Filpula et al. · 2004 [cited by applicant]
US 6756523B1 · Kahn et al. · 2004 [cited by applicant]
US 6765087B1 · Casterman et al. · 2004 [cited by applicant]
US 6809185B1 · Schoonjans et al. · 2004 [cited by applicant]
US 6818418B1 · Lipovsek et al. · 2004 [cited by applicant]
US 6833441B2 · Wang et al. · 2004 [cited by applicant]
US 6838254B1 · Hamers et al. · 2005 [cited by applicant]
US 6905680B2 · June et al. · 2005 [cited by applicant]
US 6979546B2 · Moretta et al. · 2005 [cited by applicant]
US 6982321B2 · Winter · 2006 [cited by applicant]
US 7041870B2 · Tomizuka et al. · 2006 [cited by applicant]
US 7083785B2 · Browning et al. · 2006 [cited by applicant]
US 7087409B2 · Barbas, III et al. · 2006 [cited by applicant]
US 7105149B1 · Dalla-Favera · 2006 [cited by applicant]
US 7125978B1 · Vezina et al. · 2006 [cited by applicant]
US 7129330B1 · Little et al. · 2006 [cited by applicant]
US 7183076B2 · Arathoon et al. · 2007 [cited by applicant]
US 7186804B2 · Gillies et al. · 2007 [cited by applicant]
US 7189826B2 · Rodman · 2007 [cited by applicant]
US 7250297B1 · Beste et al. · 2007 [cited by applicant]
US 7276241B2 · Schneider et al. · 2007 [cited by applicant]
US 7332581B2 · Presta · 2008 [cited by applicant]
US 7361360B2 · Kitabwalla et al. · 2008 [cited by applicant]
US 7371826B2 · Presta · 2008 [cited by applicant]
US 7402314B2 · Sherman · 2008 [cited by applicant]
US 7431380B1 · Buresh · 2008 [cited by applicant]
US 7476724B2 · Dennis et al. · 2009 [cited by applicant]
US 7498298B2 · Doronina et al. · 2009 [cited by applicant]
US 7501121B2 · Tchistiakova et al. · 2009 [cited by applicant]
US 7517966B2 · Moretta et al. · 2009 [cited by applicant]
US 7521056B2 · Chang et al. · 2009 [cited by applicant]
US 7521541B2 · Eigenbrot et al. · 2009 [cited by applicant]
US 7527787B2 · Chang et al. · 2009 [cited by applicant]
US 7527791B2 · Adams et al. · 2009 [cited by applicant]
US 7534866B2 · Chang et al. · 2009 [cited by applicant]
US 7563441B2 · Graus et al. · 2009 [cited by applicant]
US 7601803B1 · Fiedler et al. · 2009 [cited by applicant]
US 7612181B2 · Wu et al. · 2009 [cited by applicant]
US 7642228B2 · Carter et al. · 2010 [cited by applicant]
US 7700739B2 · Lacy et al. · 2010 [cited by applicant]
US 7741446B2 · Pardridge et al. · 2010 [cited by applicant]
US 7750128B2 · Gegg et al. · 2010 [cited by applicant]
US 7767429B2 · Bookbinder et al. · 2010 [cited by applicant]
US 7799902B2 · Browning et al. · 2010 [cited by applicant]
US 7803376B2 · Velardi et al. · 2010 [cited by applicant]
US 7807160B2 · Presta et al. · 2010 [cited by applicant]
US 7829289B2 · Lantz et al. · 2010 [cited by applicant]
US 7855275B2 · Eigenbrot et al. · 2010 [cited by applicant]
US 7858759B2 · Brandt et al. · 2010 [cited by applicant]
US 7906118B2 · Chang et al. · 2011 [cited by applicant]
US 7919257B2 · Hoogenboom et al. · 2011 [cited by applicant]
US 7943743B2 · Korman et al. · 2011 [cited by applicant]
US 7999077B2 · Pastan et al. · 2011 [cited by applicant]
US 8003774B2 · Stavenhagen et al. · 2011 [cited by applicant]
US 8008449B2 · Korman et al. · 2011 [cited by applicant]
US 8012465B2 · Elias et al. · 2011 [cited by applicant]
US 8034326B2 · Hjorth et al. · 2011 [cited by applicant]
US 8202517B2 · Bookbinder et al. · 2012 [cited by applicant]
US 8216805B2 · Carter et al. · 2012 [cited by applicant]
US 8227577B2 · Klein et al. · 2012 [cited by applicant]
US 8299220B2 · Dalla-Favera · 2012 [cited by applicant]
US 8354509B2 · Carven et al. · 2013 [cited by applicant]
US 8362213B2 · Elkins et al. · 2013 [cited by applicant]
US 8450470B2 · Bookbinder et al. · 2013 [cited by applicant]
US 8466260B2 · Elkins et al. · 2013 [cited by applicant]
US 8552156B2 · Takayanagi et al. · 2013 [cited by applicant]
US 8580252B2 · Bookbinder et al. · 2013 [cited by applicant]
US 8586713B2 · Davis et al. · 2013 [cited by applicant]
US 8592562B2 · Kannan et al. · 2013 [cited by applicant]
US 8609089B2 · Langermann et al. · 2013 [cited by applicant]
US 8617545B2 · Hsu et al. · 2013 [cited by applicant]
US 8617559B2 · Elkins et al. · 2013 [cited by applicant]
US 8658135B2 · O'Connor-McCourt et al. · 2014 [cited by applicant]
US 8703132B2 · Imhof-Jung et al. · 2014 [cited by applicant]
US 8772246B2 · Bookbinder et al. · 2014 [cited by applicant]
US 8790895B2 · Fiedler et al. · 2014 [cited by applicant]
US 8821883B2 · Ambrose et al. · 2014 [cited by applicant]
US 8846042B2 · Zhou · 2014 [cited by applicant]
US 8871912B2 · Davis et al. · 2014 [cited by applicant]
US 8920776B2 · Gaiger et al. · 2014 [cited by applicant]
US 8945571B2 · Mössner et al. · 2015 [cited by applicant]
US 8993524B2 · Bedi et al. · 2015 [cited by applicant]
US 9000130B2 · Bhakta et al. · 2015 [cited by applicant]
US 9034324B2 · Kalled et al. · 2015 [cited by applicant]
US 9056905B2 · Olson et al. · 2015 [cited by applicant]
US 9145588B2 · Throsby et al. · 2015 [cited by applicant]
US 9200060B2 · Kannan et al. · 2015 [cited by applicant]
US 9243058B2 · Armitage et al. · 2016 [cited by applicant]
US 9309311B2 · Gurney et al. · 2016 [cited by applicant]
US 9340621B2 · Kufer et al. · 2016 [cited by applicant]
US 9358286B2 · De et al. · 2016 [cited by applicant]
US 9359437B2 · Davis et al. · 2016 [cited by applicant]
US 9382323B2 · Brinkmann et al. · 2016 [cited by applicant]
US 9387237B2 · Kalled et al. · 2016 [cited by applicant]
US 9416187B2 · Tedder et al. · 2016 [cited by applicant]
US 9447159B2 · Ast et al. · 2016 [cited by applicant]
US 9447185B2 · Romagne et al. · 2016 [cited by applicant]
US 9545086B2 · MacKay et al. · 2017 [cited by applicant]
US 9593376B2 · Zitvogel et al. · 2017 [cited by applicant]
US 9663577B2 · Pierres et al. · 2017 [cited by applicant]
US 9676863B2 · Lo · 2017 [cited by applicant]
US 9833476B2 · Zhang et al. · 2017 [cited by applicant]
US 10150816B2 · Abbot et al. · 2018 [cited by applicant]
US 10294300B2 · Raum et al. · 2019 [cited by applicant]
US 10308721B2 · Williams et al. · 2019 [cited by applicant]
US 10478509B2 · Torgov et al. · 2019 [cited by applicant]
US 10610571B2 · Ptacin et al. · 2020 [cited by applicant]
US 10676516B2 · Viney et al. · 2020 [cited by applicant]
US 10730942B2 · Pule et al. · 2020 [cited by applicant]
US 10815311B2 · Wesche et al. · 2020 [cited by applicant]
US 11033634B2 · Stull et al. · 2021 [cited by applicant]
US 11291721B2 · Loew et al. · 2022 [cited by applicant]
US 11292838B2 · Schendel et al. · 2022 [cited by applicant]
US 11673953B2 · Zhang et al. · 2023 [cited by applicant]
US 11692031B2 · Dahlhoff et al. · 2023 [cited by applicant]
US 11845797B2 · Tan et al. · 2023 [cited by applicant]
US 11965025B2 · Tan et al. · 2024 [cited by applicant]
US 12152073B2 · Loew et al. · 2024 [cited by applicant]
US 20020004587A1 · Miller et al. · 2002 [cited by applicant]
US 20020041865A1 · Austin et al. · 2002 [cited by applicant]
US 20020062010A1 · Arathoon et al. · 2002 [cited by applicant]
US 20020076406A1 · Leung · 2002 [cited by applicant]
US 20020103345A1 · Zhu · 2002 [cited by applicant]
US 20020164328A1 · Shinkawa et al. · 2002 [cited by applicant]
US 20030115614A1 · Kanda et al. · 2003 [cited by applicant]
US 20030130496A1 · Winter et al. · 2003 [cited by applicant]
US 20030157108A1 · Presta · 2003 [cited by applicant]
US 20030175884A1 · Umana et al. · 2003 [cited by applicant]
US 20030207346A1 · Arathoon et al. · 2003 [cited by applicant]
US 20030211078A1 · Heavner · 2003 [cited by applicant]
US 20040009530A1 · Wilson et al. · 2004 [cited by applicant]
US 20040093621A1 · Shitara et al. · 2004 [cited by applicant]
US 20040109865A1 · Niwa et al. · 2004 [cited by applicant]
US 20040110282A1 · Kanda et al. · 2004 [cited by applicant]
US 20040110704A1 · Yamane et al. · 2004 [cited by applicant]
US 20040132140A1 · Satoh et al. · 2004 [cited by applicant]
US 20040175756A1 · Kolkman et al. · 2004 [cited by applicant]
US 20040219643A1 · Winter et al. · 2004 [cited by applicant]
US 20040220388A1 · Mertens et al. · 2004 [cited by applicant]
US 20040241817A1 · Umana et al. · 2004 [cited by applicant]
US 20040242847A1 · Fukushima et al. · 2004 [cited by applicant]
US 20050003403A1 · Rossi et al. · 2005 [cited by applicant]
US 20050004352A1 · Kontermann et al. · 2005 [cited by applicant]
US 20050014934A1 · Hinton et al. · 2005 [cited by applicant]
US 20050048512A1 · Kolkman et al. · 2005 [cited by applicant]
US 20050053973A1 · Kolkman et al. · 2005 [cited by applicant]
US 20050069552A1 · Bleck et al. · 2005 [cited by applicant]
US 20050079170A1 · Le Gall et al. · 2005 [cited by applicant]
US 20050079574A1 · Bond · 2005 [cited by applicant]
US 20050090648A1 · Tsurushita et al. · 2005 [cited by applicant]
US 20050100543A1 · Hansen et al. · 2005 [cited by applicant]
US 20050119455A1 · Fuh et al. · 2005 [cited by applicant]
US 20050123546A1 · Umana et al. · 2005 [cited by applicant]
US 20050136049A1 · Ledbetter et al. · 2005 [cited by applicant]
US 20050136051A1 · Scallon · 2005 [cited by applicant]
US 20050163782A1 · Glaser et al. · 2005 [cited by applicant]
US 20050260186A1 · Bookbinder et al. · 2005 [cited by applicant]
US 20050266000A1 · Bond et al. · 2005 [cited by applicant]
US 20050266425A1 · Zauderer et al. · 2005 [cited by applicant]
US 20060008844A1 · Stemmer et al. · 2006 [cited by applicant]
US 20060025576A1 · Miller et al. · 2006 [cited by applicant]
US 20060083747A1 · Winter et al. · 2006 [cited by applicant]
US 20060104968A1 · Bookbinder et al. · 2006 [cited by applicant]
US 20060120960A1 · Deyev et al. · 2006 [cited by applicant]
US 20060141581A1 · Gillies et al. · 2006 [cited by applicant]
US 20060204493A1 · Huang et al. · 2006 [cited by applicant]
US 20060263367A1 · Fey et al. · 2006 [cited by applicant]
US 20070004909A1 · Johnson et al. · 2007 [cited by applicant]
US 20070036783A1 · Humeau et al. · 2007 [cited by applicant]
US 20070061900A1 · Murphy et al. · 2007 [cited by applicant]
US 20070087381A1 · Kojima · 2007 [cited by applicant]
US 20070105105A1 · Clelland et al. · 2007 [cited by applicant]
US 20070117126A1 · Sidhu et al. · 2007 [cited by applicant]
US 20070128150A1 · Norman · 2007 [cited by applicant]
US 20070141049A1 · Bredehorst et al. · 2007 [cited by applicant]
US 20070154901A1 · Thogersen et al. · 2007 [cited by applicant]
US 20070160598A1 · Dennis et al. · 2007 [cited by applicant]
US 20070178106A1 · Romagne · 2007 [cited by applicant]
US 20070184052A1 · Lin et al. · 2007 [cited by applicant]
US 20070231322A1 · Romagne et al. · 2007 [cited by applicant]
US 20070237764A1 · Birtalan et al. · 2007 [cited by applicant]
US 20070274985A1 · Dubel et al. · 2007 [cited by applicant]
US 20070292936A1 · Barthelemy et al. · 2007 [cited by applicant]
US 20080050370A1 · Glaser et al. · 2008 [cited by applicant]
US 20080063717A1 · Romagne et al. · 2008 [cited by applicant]
US 20080069820A1 · Fuh et al. · 2008 [cited by applicant]
US 20080152645A1 · Pardridge et al. · 2008 [cited by applicant]
US 20080171855A1 · Rossi et al. · 2008 [cited by applicant]
US 20080241884A1 · Shitara et al. · 2008 [cited by applicant]
US 20080247944A1 · Graziano et al. · 2008 [cited by applicant]
US 20080254512A1 · Capon · 2008 [cited by applicant]
US 20080260738A1 · Moore et al. · 2008 [cited by applicant]
US 20080299137A1 · Svendsen et al. · 2008 [cited by applicant]
US 20090002360A1 · Chen et al. · 2009 [cited by applicant]
US 20090010843A1 · Spee et al. · 2009 [cited by applicant]
US 20090130106A1 · Christopherson et al. · 2009 [cited by applicant]
US 20090148905A1 · Ashman et al. · 2009 [cited by applicant]
US 20090155275A1 · Wu et al. · 2009 [cited by applicant]
US 20090162359A1 · Klein et al. · 2009 [cited by applicant]
US 20090162360A1 · Klein et al. · 2009 [cited by applicant]
US 20090175851A1 · Klein et al. · 2009 [cited by applicant]
US 20090175867A1 · Thompson et al. · 2009 [cited by applicant]
US 20090214533A1 · Clynes · 2009 [cited by applicant]
US 20090232811A1 · Klein et al. · 2009 [cited by applicant]
US 20090234105A1 · Gervay-Hague et al. · 2009 [cited by applicant]
US 20090263392A1 · Igawa et al. · 2009 [cited by applicant]
US 20090274649A1 · Qu et al. · 2009 [cited by applicant]
US 20090280116A1 · Smith et al. · 2009 [cited by applicant]
US 20090324538A1 · Wong et al. · 2009 [cited by applicant]
US 20100015133A1 · Igawa et al. · 2010 [cited by applicant]
US 20100015153A1 · Moretta et al. · 2010 [cited by applicant]
US 20100028330A1 · Collins et al. · 2010 [cited by applicant]
US 20100047169A1 · Mandelboim et al. · 2010 [cited by applicant]
US 20100168393A1 · Clube et al. · 2010 [cited by applicant]
US 20100260704A1 · Berenguer et al. · 2010 [cited by applicant]
US 20100316645A1 · Imhof-Jung et al. · 2010 [cited by applicant]
US 20110014659A1 · Balazs et al. · 2011 [cited by applicant]
US 20110054151A1 · Lazar et al. · 2011 [cited by applicant]
US 20110091372A1 · Ghayur et al. · 2011 [cited by applicant]
US 20110150892A1 · Thudium et al. · 2011 [cited by applicant]
US 20110177073A1 · Van Berkel et al. · 2011 [cited by applicant]
US 20110177093A1 · Kalled et al. · 2011 [cited by applicant]
US 20110250170A1 · Pedretti et al. · 2011 [cited by applicant]
US 20110287056A1 · Gu et al. · 2011 [cited by applicant]
US 20110293613A1 · Brinkmann et al. · 2011 [cited by applicant]
US 20120034221A1 · Bonvini et al. · 2012 [cited by applicant]
US 20120039906A1 · Olive · 2012 [cited by applicant]
US 20120149876A1 · Von Kreudenstein et al. · 2012 [cited by applicant]
US 20120184716A1 · Fischer et al. · 2012 [cited by applicant]
US 20120201746A1 · Liu et al. · 2012 [cited by applicant]
US 20120213768A1 · Oh et al. · 2012 [cited by applicant]
US 20120294857A1 · Sentman et al. · 2012 [cited by applicant]
US 20130017200A1 · Scheer et al. · 2013 [cited by applicant]
US 20130022601A1 · Brinkmann et al. · 2013 [cited by applicant]
US 20130078249A1 · Ast et al. · 2013 [cited by applicant]
US 20130129723A1 · Blankenship et al. · 2013 [cited by applicant]
US 20130164293A1 · Florio et al. · 2013 [cited by applicant]
US 20130165638A1 · Hsu et al. · 2013 [cited by applicant]
US 20130178605A1 · Blein et al. · 2013 [cited by applicant]
US 20130195849A1 · Spreter Von Kreudenstein et al. · 2013 [cited by applicant]
US 20130243775A1 · Papadopoulos et al. · 2013 [cited by applicant]
US 20130266568A1 · Brinkmann et al. · 2013 [cited by applicant]
US 20130267686A1 · Brinkmann et al. · 2013 [cited by applicant]
US 20130273055A1 · Borges et al. · 2013 [cited by applicant]
US 20130273089A1 · Getts et al. · 2013 [cited by applicant]
US 20130280208A1 · Stepkowski et al. · 2013 [cited by applicant]
US 20130303396A1 · Igawa et al. · 2013 [cited by applicant]
US 20130317200A1 · Elson et al. · 2013 [cited by applicant]
US 20140037621A1 · Tsurushita et al. · 2014 [cited by applicant]
US 20140044728A1 · Takayanagi et al. · 2014 [cited by applicant]
US 20140051833A1 · Fischer et al. · 2014 [cited by applicant]
US 20140051835A1 · Dixit et al. · 2014 [cited by applicant]
US 20140072528A1 · Gerdes et al. · 2014 [cited by applicant]
US 20140072581A1 · Dixit et al. · 2014 [cited by applicant]
US 20140079689A1 · Elliott et al. · 2014 [cited by applicant]
US 20140079691A1 · McConnell · 2014 [cited by examiner]
US 20140099254A1 · Chang et al. · 2014 [cited by applicant]
US 20140154254A1 · Kannan et al. · 2014 [cited by applicant]
US 20140199294A1 · Mimoto et al. · 2014 [cited by applicant]
US 20140200331A1 · Corper et al. · 2014 [cited by applicant]
US 20140227265A1 · Wu et al. · 2014 [cited by applicant]
US 20140242075A1 · Parren et al. · 2014 [cited by applicant]
US 20140242077A1 · Choi et al. · 2014 [cited by applicant]
US 20140256916A1 · Kruip et al. · 2014 [cited by applicant]
US 20140308285A1 · Yan et al. · 2014 [cited by applicant]
US 20140322212A1 · Brogdon et al. · 2014 [cited by applicant]
US 20140322221A1 · Miller et al. · 2014 [cited by applicant]
US 20140348839A1 · Chowdhury et al. · 2014 [cited by applicant]
US 20140363426A1 · Moore et al. · 2014 [cited by applicant]
US 20140377269A1 · Mabry et al. · 2014 [cited by applicant]
US 20150017187A1 · Thanos et al. · 2015 [cited by applicant]
US 20150018529A1 · Humphreys et al. · 2015 [cited by applicant]
US 20150056199A1 · Kumar et al. · 2015 [cited by applicant]
US 20150098900A1 · Ebens et al. · 2015 [cited by applicant]
US 20150133638A1 · Wranik et al. · 2015 [cited by applicant]
US 20150166661A1 · Chen et al. · 2015 [cited by applicant]
US 20150166670A1 · Castoldi et al. · 2015 [cited by applicant]
US 20150175707A1 · De Jong et al. · 2015 [cited by applicant]
US 20150203591A1 · Yancopoulos et al. · 2015 [cited by applicant]
US 20150211001A1 · Ohrn et al. · 2015 [cited by applicant]
US 20150218260A1 · Klein et al. · 2015 [cited by applicant]
US 20150232560A1 · Heindl et al. · 2015 [cited by applicant]
US 20150315296A1 · Schaefer et al. · 2015 [cited by applicant]