	US 12,252,527 B2
	CD4 muteins and methods of using the same
Michael Farzan, Juno Beach, FL (US); Matthew Gardner, Jupiter, FL (US); Ina Fetzer, Palm Beach Gardens, FL (US); Michael Alpert, Jupiter, FL (US); and Charles Bailey, Jupiter, FL (US)
Assigned to UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INCORPORATED, Gainesville, FL (US); and EMMUNE, INC., Juno Beach, FL (US)
Appl. No. 16/982,134
Filed by UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INCORPORATED, Gainesville, FL (US); and Emmune, Inc., Juno Beach, FL (US)
PCT Filed Mar. 21, 2019, PCT No. PCT/US2019/023422 § 371(c)(1), (2) Date Sep. 18, 2020, PCT Pub. No. WO2019/183387, PCT Pub. Date Sep. 26, 2019.
Claims priority of provisional application 62/645,903, filed on Mar. 21, 2018.
Prior Publication US 2023/0159616 A1, May 25, 2023
Int. Cl. C07K 14/73 (2006.01); A61P 31/18 (2006.01); C12N 15/86 (2006.01)

CPC C07K 14/70514 (2013.01) [A61P 31/18 (2018.01); C12N 15/86 (2013.01); C07K 2319/30 (2013.01); C12N 2750/14143 (2013.01)]

23 Claims

1. A protein comprising a human CD4 domain 1 and domain 2 (CD4 D1D2) mutein, wherein the CD4 D1D2 mutein is at least 90% identical to a wild-type human CD4 D1D2 of SEQ ID NO: 1, and comprises at least one substitution in the CD4 domain 1 (D1) and at least one substitution in the CD4 domain 2 (D2), wherein the CD4 D1 corresponds to amino acid residues 1 to 98 of SEQ ID NO: 1 and the CD4 D2 corresponds to amino acid residues 99 to 178 of SEQ ID NO: 1, and wherein each substitution is of

(a) a basic amino acid in wild-type human CD4 D1D2 (SEQ ID NO: 1) by an uncharged amino acid;

(b) a basic amino acid in wild-type human CD4 D1D2 (SEQ ID NO: 1) by an acidic amino acid;

(d) a glycine or an amino acid with a buried hydrophobic side chain in wild-type human CD4 D1D2 (SEQ ID NO: 1) by a hydrophobic amino acid that has a larger volume than the amino acid that is replaced;

wherein the CD4 D1D2 mutein is not identical to a naturally-occurring, wild-type non-human primate protein.