US 9,808,528 B2
Protein-polymer-drug conjugates and methods of using same
Natalya D. Bodyak, Brookline, MA (US); Timothy B. Lowinger, Carlisle, MA (US); Peter U. Park, Somerville, MA (US); and Aleksandr V. Yurkovetskiy, Littleton, MA (US)
Assigned to Mersana Therapeutics, Inc., Cambridge, MA (US)
Filed by Mersana Therapeutics, Inc., Cambridge, MA (US)
Filed on Jun. 18, 2015, as Appl. No. 14/742,936.
Claims priority of provisional application 62/013,851, filed on Jun. 18, 2014.
Claims priority of provisional application 62/034,518, filed on Aug. 7, 2014.
Claims priority of provisional application 62/147,964, filed on Apr. 15, 2015.
Prior Publication US 2015/0366982 A1, Dec. 24, 2015
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 38/08 (2006.01); A61P 35/00 (2006.01); A61K 39/395 (2006.01); A61K 45/06 (2006.01); A61K 47/48 (2006.01)
CPC A61K 45/06 (2013.01) [A61K 38/08 (2013.01); A61K 39/39558 (2013.01); A61K 47/48192 (2013.01)] 20 Claims
 
1. A method of alleviating a symptom of a cancer in a subject in need thereof, wherein the subject is identified as having low HER2 expression, comprising administering a conjugate to the subject in an amount sufficient to alleviate the symptom of the cancer, wherein the conjugate is of Formula (Ie), comprising a polymeric scaffold comprising a poly(1-hydroxymethylethylene hydroxymethyl-formal) (PHF):

OG Complex Work Unit Drawing
wherein:
the PHF has a molecular weight ranging from about 2 kDa to about 40 kDa;
PBRM is trastuzumab or a biosimilar thereof;
each occurrence of D independently is a therapeutic agent having a molecular weight of ≤5kDa, and the

OG Complex Work Unit Drawing
the between D and the carbonyl group denotes direct or indirect attachment of D to the carbonyl group,
X is CH2, O, or NH;
one of Xa and Xb is H and the other is a water-soluble maleimido blocking moiety, or Xaand Xb, together with the carbon atoms to which they are attached for a carbon-carbon double bond,
m1 is an integer from 1 to about 140,
m7 is an integer from 1 to about 40, wherein the sum of m1 and m7 is about 2 to about 180,
m is an integer from 1 to about 300,
m3a is an integer from 0 to about 17,
m3b is an integer from 1 to about 8, wherein the sum of m3a and m3b is an integer between 1 and about 18,
the sum of m, m1, m7, m3a, and m3b ranges from about 15 to about 300, and
m5is an integer from 1 to about 10.