US 12,215,143 B2
Anti-polyubiquitin multispecific antibodies
Vishva Dixit, Los Altos, CA (US); Marissa Matsumoto, Foster City, CA (US); and Erick Castellanos, South San Francisco, CA (US)
Assigned to Genentech, Inc., South San Francisco, CA (US)
Filed by Genentech, Inc., South San Francisco, CA (US)
Filed on Jan. 14, 2022, as Appl. No. 17/576,344.
Application 17/576,344 is a division of application No. 16/211,669, filed on Dec. 6, 2018, granted, now 11,274,145.
Application 16/211,669 is a continuation of application No. PCT/US2017/038940, filed on Jun. 23, 2017.
Claims priority of provisional application 62/354,305, filed on Jun. 24, 2016.
Prior Publication US 2022/0242938 A1, Aug. 4, 2022
Int. Cl. C07K 16/18 (2006.01); C12N 15/62 (2006.01); G01N 33/68 (2006.01)
CPC C07K 16/18 (2013.01) [C12N 15/62 (2013.01); G01N 33/68 (2013.01); G01N 33/6857 (2013.01); C07K 2317/31 (2013.01); C07K 2317/41 (2013.01); C07K 2317/52 (2013.01); C07K 2317/526 (2013.01); C07K 2317/565 (2013.01); C07K 2317/626 (2013.01); G01N 2440/36 (2013.01)] 15 Claims
 
1. A nucleic acid encoding a multispecific antibody that binds a mixed-topology polyubiquitin comprising a first linkage and a second linkage, the antibody comprising a first VH/VL unit specific for the first linkage, and a second VH/VL unit specific for the second linkage, wherein the first linkage and the second linkage are a K11 linkage, and a K48 linkage, or a K48 linkage and a K11 linkage, respectively, wherein the multispecific-antibody comprises first and second half antibodies, wherein,
a) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 10,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 11,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 12,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 13, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 14, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 23,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 24,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 25,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 26,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 27, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 28;
b) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 10,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 11,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 12,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 13, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 14, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 37,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 38,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 39,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 40,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 41, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 42;
c) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 9,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 10,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 11,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 12,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 13, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 14, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 51,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 52,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 53,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 54,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 55, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 56;
d) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 23,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 24,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 25,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 26,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 27, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 28, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 37,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 38,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 39,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 40,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 41, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 42;
e) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 23,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 24,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 25,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 26,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 27, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 28, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 51,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 52,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 53,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 54,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 55, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 56; or
f) one of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 37,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 38,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 39,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 40,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 41, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 42, and
the other of the first and second half antibodies comprises
(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 51,
(ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 52,
(iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 53,
(iv) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 54,
(v) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 55, and
(vi) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 56.