US 12,403,202 B2
Dosage of claudin-6 conjugates for cancer treatment
Dennis Slamon, Los Angeles, CA (US); and Neil A. O'Brien, Los Angeles, CA (US)
Assigned to The Regents of the University of California, Oakland, CA (US)
Filed by The Regents of the University of California, Oakland, CA (US)
Filed on May 24, 2024, as Appl. No. 18/674,612.
Claims priority of provisional application 63/468,817, filed on May 25, 2023.
Prior Publication US 2024/0390511 A1, Nov. 28, 2024
Int. Cl. A61K 47/68 (2017.01); A61P 35/00 (2006.01)
CPC A61K 47/6849 (2017.08) [A61P 35/00 (2018.01)] 27 Claims
 
1. A method for inhibiting a solid tumor expressing claudin-6 (CLDN6) in a human subject, comprising administering to the human subject an effective amount of a composition comprising conjugates of a CLDN6-specific antigen-binding protein covalently bound to heterologous moieties of structural formula (II):

OG Complex Work Unit Chemistry
wherein

OG Complex Work Unit Chemistry
is a bond and a sulfur atom of the CLDN6-specific antigen-binding protein;
the CLDN6-specific antigen-binding protein comprises an antibody that binds CLDN6 or antigen-binding fragment thereof comprising:
(i) HC CDR1 having a sequence GFTFSNYW (SEQ ID NO: 23);
(ii) HC CDR2 having a sequence IRLKSDNYAT (SEQ ID NO: 24),
(iii) HC CDR3 having a sequence NDGPPSGS (SEQ ID NO: 457),
(iv) LC CDR1 having a sequence ENIYSY (SEQ ID NO: 20),
(v) LC CDR2 having a sequence NAK, and
(vi) LC CDR3 having a sequence QHHYTVPWT (SEQ ID NO: 22);
a first plurality of the conjugates are bound to four heterologous moieties of structural formula (II);
at least about 95% of the first plurality of conjugates are structurally homogenous;
the average number of heterologous moieties per CLDN6-specific antigen-binding protein in the composition is about 3.5 to about 4;
the effective amount is in a range of about 2.4 mg/kg to 4.0 mg/kg; and
a dose normalized Cmax value for unbound circulating monomethyl auristatin E (MMAE) is less than about 35 μg/mL per mg of the conjugate after administration of the composition, thereby minimizing toxicity in the subject and inhibiting the solid tumor.