US 12,215,164 B2
Immunotoxins with albumin binding domain
Ira H. Pastan, Chevy Chase, MD (US); Junxia Wei, Rockville, MD (US); Masanori Onda, Germantown, MD (US); Tapan Bera, Frederick, MD (US); and Mitchell Ho, Urbana, MD (US)
Assigned to The United States of America, as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US)
Filed by The United States of America,as represented by the Secretary,Department of Health and Human Services, Bethesda, MD (US)
Filed on Sep. 20, 2023, as Appl. No. 18/471,137.
Application 18/471,137 is a division of application No. 16/648,369, granted, now 11,795,235, previously published as PCT/US2018/051418, filed on Sep. 18, 2018.
Claims priority of provisional application 62/559,926, filed on Sep. 18, 2017.
Prior Publication US 2024/0132619 A1, Apr. 25, 2024
Prior Publication US 2024/0228657 A9, Jul. 11, 2024
Int. Cl. C07K 16/30 (2006.01); C07K 14/21 (2006.01); C07K 16/28 (2006.01)
CPC C07K 16/30 (2013.01) [C07K 14/21 (2013.01); C07K 16/2803 (2013.01); C07K 16/2866 (2013.01); C07K 16/2878 (2013.01); C07K 2317/31 (2013.01); C07K 2317/569 (2013.01); C07K 2317/624 (2013.01); C07K 2317/73 (2013.01); C07K 2317/94 (2013.01); C07K 2319/33 (2013.01); C07K 2319/50 (2013.01); C07K 2319/55 (2013.01); C07K 2319/70 (2013.01)] 23 Claims
 
1. A nucleic acid comprising a nucleotide sequence encoding a molecule, the molecule comprising:
(a) a first domain, which comprises a targeting moiety, wherein the targeting moiety is not an affibody;
(b) a second domain, which comprises an albumin binding domain (ABD) and comprises the amino acid sequence of SEQ ID NO: 2,
(c) a third domain, which comprises a furin cleavage sequence (FCS) which FCS is cleavable by furin; and
(d) a fourth domain, which comprises a Domain III from Pseudomonas exotoxin A (PE) or a Domain III from Pseudomonas exotoxin A (PE) comprising a substitution of one or more amino acid residues;
wherein the second domain is positioned between the first domain and the third domain;
wherein the third domain is positioned between the second domain and the fourth domain; and
wherein the molecule optionally has (i) a substitution of one or more amino acid residues within one or more T-cell epitopes, (ii) a substitution of one or more amino acid residues within one or more B cell epitopes, (iii) a deletion of one or more contiguous amino acid residues of residues 1-273 and 285-394 as defined by SEQ ID NO: 1; or (iv) a combination of any of (i)-(iii).