	US 12,258,393 B2
	Method of treating inflammatory bowel disease with a combination therapy of antibodies to IL-23 and TNF alpha
Matthew Germinaro, Philadelphia, PA (US); Christopher O'Brien, Lafayette Hill, PA (US); Jacqueline Perrigoue, Oreland, PA (US); and Marion Vetter, Spring House, PA (US)
Assigned to Janssen Biotech, Inc., Horsham, PA (US)
Filed by Janssen Biotech, Inc., Horsham, PA (US)
Filed on May 20, 2021, as Appl. No. 17/325,743.
Claims priority of provisional application 63/116,383, filed on Nov. 20, 2020.
Claims priority of provisional application 63/028,219, filed on May 21, 2020.
Prior Publication US 2021/0363234 A1, Nov. 25, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/00 (2006.01); A61P 1/04 (2006.01); A61P 37/02 (2006.01); C07K 16/24 (2006.01)

CPC C07K 16/244 (2013.01) [A61P 1/04 (2018.01); A61P 37/02 (2018.01); C07K 16/241 (2013.01); A61K 2039/505 (2013.01); C07K 2317/565 (2013.01)]

7 Claims

1. A method comprising:

a) administering to a group of patients with ulcerative colitis a first co-therapeutically effective amount of an anti-IL-23p19 antibody comprising (i) the heavy chain complementarity determining region (CDR) amino acid sequences of SEQ ID NOS: 1-3 and the light chain CDR amino acid sequences of SEQ ID NOS: 4-6, (ii) the heavy chain variable region amino acid sequence of SEQ ID NO: 7 and the light chain variable region amino acid sequence of SEQ ID NO: 8, or (iii) the heavy chain amino acid sequence of SEQ ID NO: 9 and the light chain amino acid sequence of SEQ ID NO: 10;

b) administering to the group of patients with ulcerative colitis a second co-therapeutically effective amount of anti-TNF-α antibody comprising (i) the heavy chain CDR amino acid sequences of SEQ ID NOS: 11-13 and the light chain CDR amino acid sequences of SEQ ID NOS: 14-16, (ii) the heavy chain variable region amino acid sequence of SEQ ID NO: 17 and the light chain variable region amino acid sequence of SEQ ID NO: 18, or (iii) the heavy chain amino acid sequence of SEQ ID NO: 19 and the light chain amino acid sequence of SEQ ID NO: 20,

wherein the anti-TNF-α antibody and the anti-IL-23p19 antibody are administered in a ratio of from 1:2 to 2:1 (w/w); and

c) achieving one or more of the following clinical endpoints at week 12:

i. greater than 83 % of patients are in clinical response defined as a decrease from baseline in the Mayo score %≥30% and ≥3 points with either decrease form baseline in the rectal bleeding subscore (RBS) of ≥1 or a RBS of 0 or 1;

ii. greater that 36% of patients are in clinical remission defined as the Mayo score≤2 with no individual subscore>1;

iii. greater than 49% of patients have endoscopic healing defined as an endoscopy score of 0 or 1;

iv. greater than 80 % of patients have a modified Mayo response defined as a decrease form baseline in the modified Mayo score of ≥2 and ≥30%, plus a decrease in rectal bleeding subscore of ≥1 or an absolute rectal bleeding subscore of ≤1, wherein the modified Mayo score is calculated as the sub of the stool frequency, rectal bleeding, and endoscopy subscores; and

v. greater than 46% of patients are in clinical remission by health authority definition defined as a stool frequency subscore of 0 or 1, rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from baseline.