US 12,071,476 B2
IL-6 antibodies and fusion constructs and conjugates thereof
Rachel D. Jacobson, Belmont, CA (US); Fernando Corrêa, Hayward, CA (US); Hong Liang, Hillsborough, CA (US); and Daniel Victor Perlroth, Palo Alto, CA (US)
Assigned to KODIAK SCIENCES INC., Palo Alto, CA (US)
Filed by KODIAK SCIENCES INC., Palo Alto, CA (US)
Filed on Mar. 1, 2019, as Appl. No. 16/290,128.
Claims priority of provisional application 62/727,950, filed on Sep. 6, 2018.
Claims priority of provisional application 62/637,575, filed on Mar. 2, 2018.
Prior Publication US 2019/0270806 A1, Sep. 5, 2019
Int. Cl. C07K 16/24 (2006.01); A61K 9/00 (2006.01); A61K 9/08 (2006.01); A61K 47/59 (2017.01); A61K 47/60 (2017.01); A61K 47/68 (2017.01); A61P 3/10 (2006.01); A61P 27/02 (2006.01); C07K 14/705 (2006.01)
CPC C07K 16/248 (2013.01) [A61K 9/0048 (2013.01); A61K 9/08 (2013.01); A61K 47/59 (2017.08); A61K 47/60 (2017.08); A61K 47/6883 (2017.08); A61P 3/10 (2018.01); A61P 27/02 (2018.01); C07K 14/705 (2013.01); C07K 2317/31 (2013.01); C07K 2317/52 (2013.01); C07K 2317/73 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01); C07K 2319/00 (2013.01); C07K 2319/30 (2013.01)] 39 Claims
 
1. A protein construct comprising an antagonist IL-6 antibody fused to a VEGF trap, wherein the antibody comprises a heavy chain and a light chain, wherein
(i) the heavy chain comprises the amino acid sequence of any one of SEQ ID NOs: 19-27, or comprises a heavy chain variable region (VH) comprising the amino acid sequence of any one of SEQ ID NOs: 7-13, 89, 90, 256-262; and the light chain that comprises the amino acid sequence of any one of SEQ ID NOs: 28-30, or comprises a light chain variable region (VL) comprising the amino acid sequence of any one of SEQ ID NOs: 91-93; or
(ii) the heavy chain comprises a heavy chain variable region (VH) comprising 3 complementarity determining regions (CDRs): VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence from the CDR1, CDR2 and CDR3, respectively, in SEQ ID NO: 256; and the light chain comprises a light chain variable region (VL) comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence from the CDR1, CDR2, and CDR3, respectively, in one of SEQ ID NOs: 91-93; or
(iii) the antibody comprises:
a CDRH1 comprising the amino acid sequence in SEQ ID NO: 172;
a CDRH2 comprising the amino acid sequence in SEQ ID NO: 173;
a CDRH3 comprising the amino acid sequence in SEQ ID NO: 174:
a CDRL1 comprising the amino acid sequence in SEQ ID NO: 199;
a CDRL2 comprising the amino acid sequence in SEQ ID NO: 200;
a CDRL3 comprising the amino acid sequence in SEQ ID NO: 201; and
an Fc domain comprising:
at least one of the following mutations (EU numbering): L234A, L235A, and G237A; and/or
at least one of the following mutations (EU numbering): Q347C or L443C,
wherein either:
(a) the VEGF Trap is positioned at the N-terminal end of the heavy chain comprising IL-6 VH; or
(b) the heavy chain comprises a hinge region and a CH1 domain, wherein the VEGF Trap is positioned between the hinge region and the CH1 domain of the heavy chain comprising IL-6 VH.