US2022098311A1PendingUtilityA1

Flt3 binding proteins and methods of use

64
Assignee: HARPOON THERAPEUTICS INCPriority: Feb 21, 2020Filed: Oct 12, 2021Published: Mar 31, 2022
Est. expiryFeb 21, 2040(~13.6 yrs left)· nominal 20-yr term from priority
Inventors:Holger WescheRichard J. Austin
C07K 2317/622C07K 2317/569C07K 16/2863C07K 16/2809C07K 16/18A61K 2039/505C07K 2317/92C07K 2317/73C07K 2317/31A61P 35/00C07K 2317/94C07K 2317/732C07K 2317/22A61P 35/02C07K 2317/565C07K 2317/33C07K 2317/24
64
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Claims

Abstract

Provided herein are FLT3 binding proteins, pharmaceutical compositions comprising such proteins or fragments thereof, as well as nucleic acids, recombinant expression vectors and host cells for making such FLT3 binding proteins. Also disclosed are methods of using the disclosed FLT3 binding proteins in the prevention, and/or treatment of diseases, conditions and disorders.

Claims

exact text as granted — not AI-modified
1 .- 30 . (canceled) 
     
     
         31 . An FLT3 binding domain comprising at least three complementarity determining regions (a CDR1, a CDR2, and a CDR3), wherein
 a) the CDR1 comprises the amino acid sequence of SEQ ID NO: 100, the CDR2 comprises the amino acid sequence of SEQ ID NO: 151, and the CDR3 comprises the amino acid sequence of SEQ ID NO: 186;   b) the CDR1 comprises the amino acid sequence of SEQ ID NO: 89, the CDR2 comprises the amino acid sequence of SEQ ID NO: 393, and the CDR3 comprises the amino acid sequence of SEQ ID NO: 173; or   c) the CDR1 comprises the amino acid sequence of SEQ ID NO: 89, the CDR2 comprises the amino acid sequence of SEQ ID NO: 394, and the CDR3 comprises the amino acid sequence of SEQ ID NO: 195.   
     
     
         32 . The FLT3 binding domain of  claim 31 , comprising an amino acid sequence that is at least 80% identical to a sequence selected from the group consisting of SEQ ID Nos. 73, 389, or 390. 
     
     
         33 . The FLT3 binding domain of  claim 31 , comprising an amino acid sequence selected from the group consisting of SEQ ID Nos. 73, 389, or 390. 
     
     
         34 . The FLT3 binding domain of  claim 33 , wherein the FLT3 binding domain is a single domain antibody (sdAb). 
     
     
         35 . The FLT3 binding domain of  claim 31 , wherein the FLT3 binding domain is part of a bispecific antibody. 
     
     
         36 . The FLT3 binding domain of  claim 34 , wherein the bispecific antibody comprises a CD3 binding domain. 
     
     
         37 . The FLT3 binding domain of  claim 36 , wherein the CD3 binding domain is a single chain variable fragment (scFv). 
     
     
         38 . The FLT3 binding domain of  claim 37 , wherein the CD3 is a human CD3. 
     
     
         39 . The FLT3 binding domain of  claim 31 , wherein the FLT3 binding domain is part of a multispecific antibody. 
     
     
         40 . A multispecific antibody comprising the FLT3 binding domain of  claim 31 , a CD3 binding domain and an albumin binding domain. 
     
     
         41 . The multispecific antibody of  claim 39 , wherein the CD3 binding domain is an scFv. 
     
     
         42 . The multispecific antibody of  claim 40 , wherein the CD3 binding domain comprises the amino acid sequence of SEQ ID No. 373. 
     
     
         43 . The multispecific antibody of  claim 40 , wherein the CD3 is a human CD3. 
     
     
         44 . The multispecific antibody of  claim 40 , wherein the albumin binding domain is a single domain antibody (sdAb). 
     
     
         45 . The multispecific antibody of  claim 40 , wherein the albumin binding domain comprises the amino acid sequence of SEQ ID No. 372. 
     
     
         46 . The multispecific antibody of  claim 40 , wherein the albumin is a human serum albumin. 
     
     
         47 . The multispecific antibody of  claim 40 , wherein the multispecific antibody is a single chain polypeptide and the FLT3 binding domain, the CD3 binding domain, and the albumin binding domain are joined in any order from N-terminus to C-terminus. 
     
     
         48 . The multispecific antibody of  claim 40 , wherein multispecific antibody comprises an amino acid sequence selected from the group consisting of SEQ ID Nos. 269, 391, and 392. 
     
     
         49 . The FLT3 binding domain of  claim 31 , wherein the FLT3 binding domain binds to human FLT3. 
     
     
         50 . An FLT3 targeting trispecific protein comprising (A) a first domain that binds a human CD3; (B) a second domain that binds a human serum albumin protein; and (C) a third domain that binds a human FLT3, wherein the third domain that binds the human FLT3 comprises at least three complementarity determining regions (a CDR1, a CDR2, and a CDR3), wherein
 a) the CDR1 comprises the amino acid sequence of SEQ ID NO: 100, the CDR2 comprises the amino acid sequence of SEQ ID NO: 151, and the CDR3 comprises the amino acid sequence of SEQ ID NO: 186;   b) the CDR1 comprises the amino acid sequence of SEQ ID NO: 89, the CDR2 comprises the amino acid sequence of SEQ ID NO: 393, and the CDR3 comprises the amino acid sequence of SEQ ID NO: 173; or   c) the CDR1 comprises the amino acid sequence of SEQ ID NO: 89, the CDR2 comprises the amino acid sequence of SEQ ID NO: 394, and the CDR3 comprises the amino acid sequence of SEQ ID NO: 195.   
     
     
         51 . The FLT3 targeting trispecific protein of  claim 50 , wherein the first domain is an scFv that comprises a heavy chain comprising HC CDR1, HC CDR2, HC CDR3, and a light chain comprising LC CDR1, LC CDR2, or LC CDR3, wherein the HC CDR1 comprises the amino acid sequence of SEQ ID NO: 397; the HC CDR2 comprises the amino acid sequence of SEQ ID NO: 398; the HC CDR3 comprises the amino acid sequence of SEQ ID NO: 399; the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 400; the LC CDR2 comprises the amino acid sequence of SEQ ID NO: 401; and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 402. 
     
     
         52 . The FLT3 targeting trispecific protein of  claim 51 , wherein the first domain comprises an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID No. 373. 
     
     
         53 . The FLT3 targeting trispecific protein of  claim 50 , wherein the second domain is an sdAb that comprises a CDR1, a CDR2, and a CDR3, wherein the CDR1 comprises the amino acid sequence of SEQ ID NO: 403 the CDR2 comprises the amino acid sequence of SEQ ID NO: 404; and the CDR3 comprises the amino acid sequence of SEQ ID NO: 405. 
     
     
         54 . The FLT3 targeting trispecific protein of  claim 53 , wherein the second domain comprises an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID No. 372. 
     
     
         55 . A method of treating a hematologic malignancy in a subject, the method comprising administering to the subject a FLT3 targeting trispecific protein according to  claim 50 . 
     
     
         56 . The method of  claim 55 , wherein the third domain that binds to a human FLT3 comprises an amino acid sequence that is at least 80% identical to a sequence selected from the group consisting of SEQ ID NO: 73, 389, or 390. 
     
     
         57 . The method of  claim 56 , wherein the trispecific protein comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 269, 391, and 392. 
     
     
         58 . The method of  claim 57 , wherein the hematologic malignancy is an acute myeloid leukemia (AML), a myelodysplastic syndrome, or a chronic myelomonocytic leukemia.

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