US 11,938,192 B2
Dosage regimes for the administration of an anti-CD19 ADC
Jay Marshall Feingold, Murray Hill, NJ (US); and David Rodney Ungar, Murray Hill, NJ (US)
Assigned to MEDIMMUNE LIMITED, Cambridge (GB); and ADC THERAPEUTICS SA, Epalinges (CH)
Filed by ADC THERAPEUTICS SA, Epalinges (CH); and MEDIMMUNE LIMITED, Cambridge (GB)
Filed on Mar. 18, 2022, as Appl. No. 17/699,065.
Application 17/699,065 is a continuation of application No. 16/622,649, granted, now 11,318,211, previously published as PCT/EP2018/065873, filed on Jun. 14, 2018.
Claims priority of application No. 1709440 (GB), filed on Jun. 14, 2017; application No. 1709444 (GB), filed on Jun. 14, 2017; application No. 1710494 (GB), filed on Jun. 30, 2017; application No. 1710495 (GB), filed on Jun. 30, 2017; application No. 1720542 (GB), filed on Dec. 8, 2017; application No. 1720543 (GB), filed on Dec. 8, 2017; application No. 1802679 (GB), filed on Feb. 20, 2018; and application No. 1808473 (GB), filed on May 23, 2018.
Prior Publication US 2022/0280651 A1, Sep. 8, 2022
Int. Cl. A61K 47/68 (2017.01); A61K 31/5517 (2006.01); A61P 35/02 (2006.01); C07K 16/28 (2006.01); A61K 9/00 (2006.01); A61K 31/519 (2006.01); A61K 31/573 (2006.01); A61K 31/7068 (2006.01); A61K 39/00 (2006.01)
CPC A61K 47/6803 (2017.08) [A61K 31/5517 (2013.01); A61K 47/6849 (2017.08); A61K 47/6867 (2017.08); A61P 35/02 (2018.01); C07K 16/2827 (2013.01); A61K 9/0019 (2013.01); A61K 9/0053 (2013.01); A61K 31/519 (2013.01); A61K 31/573 (2013.01); A61K 31/7068 (2013.01); A61K 2039/505 (2013.01); A61K 2039/542 (2013.01); A61K 2039/545 (2013.01); C07K 16/2887 (2013.01)] 19 Claims
 
1. A method of treating a subject suffering from a proliferative disease, said method comprising:
administering to a subject suffering from a proliferative disease an effective amount of a CD19-antibody drug conjugate (ADC),
wherein (i) the CD19-ADC comprises as the a pyrrolobenzodiazepine (PBD) dimer, linked to an antibody that binds to CD19; and (ii) the CD19-ADC has a drug to antibody ratio (DAR) of between 1 and 8,
wherein (i) the CD19-ADC is administered to the subject in a dosage regime comprising at least two treatment cycles; and (ii) the dose of CD19-ADC is reduced following the second treatment cycle; and
wherein (i) the proliferative disease is a CD19+ cancer or a CD19+ autoimmune disease; and (ii) the PBD dimer is of formula I:

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wherein
(a) RL1′ is a linker for connection to Ab, wherein RL1′ is

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wherein the wavy line indicates the point of attachment to the Ab and the asterisk indicates the point of attachment to the nitrogen in Formula (I);
(b) (i) R20 and R21 either together form a double bond between the nitrogen and carbon atoms to which they are bound; or (ii) R20 is a capping group RC, and R21 is OH;
(c) m is 0 or 1; and
(d) when there is a double bond between C2 and C3, R2 is methyl;

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when there is a single bond between C2 and C3, R2 is either H or
when there is a double bond between C2′ and C3′, R12 is methyl;
when there is a single bond between C2′ and C3′, R12 is H or

OG Complex Work Unit Chemistry