	US 12,030,934 B2
	Modified immunoglobulins for targeting amyloid deposits
Jonathan S. Wall, Knoxville, TN (US); James S. Foster, Knoxville, TN (US); and Spencer Guthrie, San Francisco, CA (US)
Assigned to Attralus, Inc., Burlingame, CA (US); and UNIVERSITY OF TENNESSEE RESEARCH FOUNDATION, Knoxville, TN (US)
Filed by Attralus, Inc., San Francisco, CA (US); and UNIVERSITY OF TENNESSEE RESEARCH FOUNDATION, Knoxville, TN (US)
Filed on Mar. 9, 2023, as Appl. No. 18/181,489.
Application 18/181,489 is a continuation of application No. 17/776,827, previously published as PCT/US2020/060596, filed on Nov. 13, 2020.
Claims priority of provisional application 63/074,912, filed on Sep. 4, 2020.
Claims priority of provisional application 62/936,002, filed on Nov. 15, 2019.
Prior Publication US 2023/0265178 A1, Aug. 24, 2023
Int. Cl. C07K 16/18 (2006.01); A61K 47/68 (2017.01); A61P 25/28 (2006.01); C12N 15/85 (2006.01); A61K 39/00 (2006.01)

CPC C07K 16/18 (2013.01) [A61K 47/6843 (2017.08); A61P 25/28 (2018.01); C12N 15/85 (2013.01); A61K 2039/505 (2013.01); C07K 2317/24 (2013.01); C07K 2317/52 (2013.01); C07K 2317/55 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C07K 2317/92 (2013.01); C07K 2317/94 (2013.01); C07K 2319/00 (2013.01); C07K 2319/01 (2013.01)]

30 Claims

1. A modified immunoglobulin, comprising:

(i) an amyloid-reactive peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:1-14; and

(ii) an Ig antibody or functional fragment thereof that binds to human amyloid fibrils, wherein the Ig antibody or functional fragment thereof comprises a light chain comprising a light chain variable region (VL) and a heavy chain comprising a heavy chain variable region (VH), wherein:

a) the VL comprises a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs:64-70, a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:21, and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:22, and the VH comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:17, a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:18, and a CDR-H3 comprising the amino acid sequence LDY;

b) the VL comprises a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:20; a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:21, and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:22, and the VH comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:17, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs:71-81; and a CDR-H3 comprising the amino acid sequence LDY; or

c) the VL comprises a CDR-L1 comprising the amino acid sequence set forth in any one of SEQ ID NOs:64-70, a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:21, and a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:22, and the VH comprises a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:17, a CDR-H2 comprising the amino acid sequence set forth in any one of SEQ ID NOs:71-81; and a CDR-H3 comprising the amino acid sequence LDY; and

wherein the modified immunoglobulin is a fusion protein comprising the Ig antibody or functional fragment thereof joined to the amyloid-reactive peptide.