	US 12,281,153 B2
	Combination therapy with targeted 4-1BB (CD137) agonists
Christina Claus, Ennetbaden (CH); Claudia Ferrara Koller, Zug (CH); Christian Klein, Bonstetten (CH); Johannes Sam, Baden (CH); and Pablo Umana, Wollerau (CH)
Assigned to Hoffmann-La Roche Inc., Little Falls, NJ (US)
Filed by Hoffmann-La Roche Inc., Little Falls, NJ (US)
Filed on Sep. 11, 2020, as Appl. No. 17/017,942.
Application 17/017,942 is a continuation of application No. PCT/EP2019/056067, filed on Mar. 12, 2019.
Claims priority of application No. 18161340 (EP), filed on Mar. 13, 2018.
Prior Publication US 2021/0095002 A1, Apr. 1, 2021
Int. Cl. C07K 14/705 (2006.01); A61K 39/00 (2006.01); A61K 39/395 (2006.01); A61P 35/00 (2006.01); C07K 16/28 (2006.01); C07K 16/30 (2006.01); C07K 16/32 (2006.01); C07K 16/40 (2006.01)

CPC C07K 14/70575 (2013.01) [A61K 39/39541 (2013.01); A61K 39/39558 (2013.01); A61P 35/00 (2018.01); C07K 16/2878 (2013.01); C07K 16/3007 (2013.01); C07K 16/32 (2013.01); C07K 16/40 (2013.01); A61K 2039/507 (2013.01); C07K 2317/31 (2013.01); C07K 2319/30 (2013.01); C07K 2319/33 (2013.01)]

24 Claims

1. A method for treating or delaying progression of a HER2-positive cancer in a subject comprising administering to the subject an effective amount of a 4-1BB agonist and an effective amount of a HER-2 targeting agent, wherein the HER-2 targeting agent is trastuzumab, pertuzumab, and/or trastuzumab emtansine, wherein the 4-1BB agonist is an antigen binding molecule comprising at least one antigen binding domain capable of specific binding to a tumor-associated antigen,

wherein the 4-1BB agonist is a molecule comprising three ectodomains of 4-1BBL or 4-1BB-binding fragments thereof and wherein the ectodomains of 4-1BBL comprise the amino acid sequence of SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO: 6, SEQ ID NO:7 or SEQ ID NO:8 and an IgG1 Fc domain comprising the amino acid substitutions L234A, L235A and P329G, as numbered according to EU numbering.