US 11,753,464 B2
Methods and compositions for targeting polyubiquitin
Robert F. Kelley, San Bruno, CA (US); and Marissa L. Matsumoto, Foster City, CA (US)
Assigned to Genentech, Inc., South San Francisco, CA (US)
Filed by Genentech, Inc., South San Francisco, CA (US)
Filed on Sep. 16, 2020, as Appl. No. 17/22,387.
Application 17/022,387 is a division of application No. 16/021,248, filed on Jun. 28, 2018, granted, now 10,808,028.
Application 16/021,248 is a division of application No. 15/153,644, filed on May 12, 2016, granted, now 10,035,849, issued on Jul. 31, 2018.
Application 15/153,644 is a division of application No. 14/732,243, filed on Jun. 5, 2015, granted, now 9,365,642, issued on Jun. 14, 2016.
Application 13/361,093 is a division of application No. 12/355,531, filed on Jan. 16, 2009, granted, now 8,133,488, issued on Mar. 13, 2012.
Application 14/732,243 is a continuation of application No. 13/361,093, filed on Jan. 30, 2012, granted, now 9,081,015, issued on Jul. 14, 2015.
Claims priority of provisional application 61/127,862, filed on May 16, 2008.
Claims priority of provisional application 61/011,577, filed on Jan. 18, 2008.
Prior Publication US 2021/0115120 A1, Apr. 22, 2021
Int. Cl. A61K 39/00 (2006.01); C07K 16/18 (2006.01); G01N 33/68 (2006.01); C07K 14/47 (2006.01)
CPC C07K 16/18 (2013.01) [C07K 14/47 (2013.01); G01N 33/68 (2013.01); C07K 2317/14 (2013.01); C07K 2317/21 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/35 (2013.01); C07K 2317/51 (2013.01); C07K 2317/515 (2013.01); C07K 2317/55 (2013.01); C07K 2317/56 (2013.01); C07K 2317/565 (2013.01); C07K 2317/92 (2013.01); G01N 2333/47 (2013.01); G01N 2440/36 (2013.01)] 19 Claims
 
1. An isolated antibody or antigen-binding fragment thereof that specifically binds to K63-linked polyubiquitin, comprising: the HVR-L1 sequence of SEQ ID NO: 3; the HVR-L2 sequence of SEQ ID NO: 16, optionally having a substitution of an F at position 1 and an A at position 2, or one substitution selected from the following:
(i) an A at position 2,
(ii) a V at position 4, or
(iii) an S at position 4;
the HVR-L3 sequence of SEQ ID NO: 4;
the HVR-H1 sequence of SEQ ID NO: 5;
the HVR-H2 sequence of SEQ ID NO: 68, wherein
(a) if HVR-L2 is unsubstituted SEQ ID NO: 16, then HVR-H2 is unsubstituted SEQ ID NO: 68,
(b) if HVR-L2 is SEQ ID NO: 16 substituted with an F at position 1 and an A at position 2, then HVR-H2 has a substitution of an S at position 8 of SEQ ID NO: 68,
(c) if HVR-L2 is SEQ ID NO: 16 substituted with an A at position 2, then HVR-H2 is SEQ ID NO: 68 substituted with an S at position 8, or with a V and S at positions 3 and 8, respectively, or with a D, S, and S at positions 1, 3, and 8, respectively,
(d) if HVR-L2 is SEQ ID NO: 16 substituted with a V at position 4, then HVR-H2 is SEQ ID NO: 68 substituted with a Y and S at positions 3 and 8 of SEQ ID NO: 68, respectively, or with a T and S at positions 3 and 8 of SEQ ID NO: 68, respectively, and
(e) if HVR-L2 is SEQ ID NO: 16 substituted with an S at position 4, then HVR-H2 is SEQ ID NO: 68 substituted with an S at position 8 of SEQ ID NO: 68 or with a T and F at positions 3 and 8 of SEQ ID NO: 68, respectively, and
the HVR-H3 sequence of SEQ ID NO: 6.