US 12,311,032 B2
Anti-Ror2 antibodies, antibody fragments, their immunoconjugates and uses thereof
Jay M. Short, Jackson, WY (US); Hwai Wen Chang, San Marcos, CA (US); and Gerhard Frey, San Diego, CA (US)
Assigned to BioAlta, Inc., San Diego, CA (US)
Filed by BioAtla, Inc., San Diego, CA (US)
Filed on Aug. 29, 2023, as Appl. No. 18/457,861.
Application 18/457,861 is a continuation of application No. 17/533,852, filed on Nov. 23, 2021, granted, now 11,879,011.
Application 17/533,852 is a continuation of application No. 16/088,769, granted, now 11,254,742, issued on Feb. 22, 2022, previously published as PCT/US2017/032357, filed on May 12, 2017.
Claims priority of provisional application 62/447,218, filed on Jan. 17, 2017.
Claims priority of provisional application 62/335,719, filed on May 13, 2016.
Prior Publication US 2024/0092901 A1, Mar. 21, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/395 (2006.01); A61K 38/07 (2006.01); A61K 47/68 (2017.01); A61P 35/00 (2006.01); C07K 16/28 (2006.01); A61K 39/00 (2006.01)
CPC A61K 47/6849 (2017.08) [A61K 38/07 (2013.01); A61K 39/3955 (2013.01); A61K 47/6803 (2017.08); A61K 47/68031 (2023.08); A61K 47/6811 (2017.08); A61P 35/00 (2018.01); C07K 16/28 (2013.01); C07K 16/2803 (2013.01); A61K 2039/505 (2013.01); C07K 2317/24 (2013.01); C07K 2317/33 (2013.01)] 24 Claims
OG exemplary drawing
 
1. A method of treating cancer comprising administering to a subject in need of such treatment,
(i) an antibody or antigen-binding fragment thereof that specifically binds to ROR2 protein, said antibody or antigen-binding fragment thereof comprising:
a heavy chain variable region including three complementarity determining regions, said regions having H1, H2, and H3 sequences, wherein:
the H1 sequence is GYTX1TEX2X3X4H (SEQ ID NO: 1);
the H2 sequence is X5X6X7X8NNGGTGYNQKFKG (SEQ ID NO: 2); and
the H3 sequence is X9X10X11SX12YX13YX14X15SYFX16X17X18 (SEQ ID NO: 3);
wherein
X1 is F or E,
X2 is Y or D,
X3 is T or C,
X4 is M or D or E or Y,
X5 is G or S,
X6 is I or E,
X7 is N or C or L or V,
X8 is T or D or E,
X9 is A or M or T,
X10 is R or H,
X11 is G,
X12 is L or F,
X13 is S,
X14 is G,
X15 is N or E,
X16 is D or L,
X17 is Y or T, and
X18 is W or L; and
a light chain variable region including three complementarity determining regions, said regions having L1, L2, and L3 sequences, wherein:
the L1 sequence is SATSSX19X20X21MX22 (SEQ ID NO: 7);
the L2 sequence is X23TSNLAS (SEQ ID NO: 8); and
the L3 sequence is QX24X25SX26YPFX27X28 (SEQ ID NO: 9);
wherein
X19 is V or E,
X20 is S or D,
X21 is Y or C or D,
X22 is H or G or L,
X23 is G or C or H or P,
X24 is Q or E,
X25 is R or H,
X26 is S or G or I or Q,
X27 is T or D, and
X28 is F or D or E,
wherein the antibody or antigen-binding fragment thereof has a total of one or two mutations in the heavy chain and light chain complementarity determining regions H1, H2, H3, L1, L2, and L3, and the one or two mutations are determined in comparison with the complementarity determining regions H1, H2, H3, L1, L2, and L3 of the parental antibody or antigen-binding fragment thereof in which X1 to X28 are F, Y, T, M, G, I, N, T, A, R, G, L, S, G, N, D, Y, W, V, S, Y, H, G, Q, R, S, T, and F, respectively; and
wherein the antibody or antigen-binding fragment thereof has a ratio of binding affinity to the ROR2 protein at pH 6.0 to binding affinity to the ROR2 protein at pH 7.4 of at least 1.5; and
(ii) at least one of external beam radiotherapy and brachytherapy.