主权项 |
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(l-hydroxymethylethylene hydroxymethyl-formal) (PHF):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 <5 kDa, and thebetween 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 Xa and 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 m5 is an integer from 1 to about 10. |