Back to results
US 12,630,599 B2Granted
CA2 compositions and methods for tunable regulation
AssigneeObsidian Therapeutics, Inc.
InventorsMichelle Lynn Ols, Vipin Suri, Dexue Sun, Dhruv Kam Sethi, Michael Schebesta, Michelle Lois Fleury, Kutlu Goksu Elpek
Life of this patent
Estimating the term…
Abstract
The present disclosure provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities.
Claims27
A polypeptide comprising an effector module, said effector module comprising:
- a. a stimulus response element (SRE), wherein the SRE comprises a drug responsive domain (DRD), said DRD comprising human carbonic anhydrase 2 (CA2;
- SEQ ID NO. 5810) or a region thereof, wherein the region of human CA2 corresponds to amino acids 2 to 260 of SEQ ID NO. 5810;
- and
- wherein the DRD comprises a mutation or set of mutations selected the group consisting of:
- (i) a R27L mutation in the amino acid at position 27 (R27) of SEQ ID NO. 5810, a T87I mutation in the amino acid at position 87 (T87) of SEQ ID NO. 5810, a N252D mutation in the amino acid at position 252 (N252) of SEQ ID NO. 5810, and a H122Y mutation in the amino acid position 122 (H122) of SEQ ID NO:5810;
- (ii) a I59N mutation in the amino acid at position 59 (159) of SEQ ID NO. 5810;
- (iii) a G102R mutation in the amino acid at position 102 (G102) of SEQ ID NO. 5810;
- (iv) a L156H mutation in the amino acid at position 156 (L156) of SEQ ID NO. 5810;
- (v) four mutations relative to SEQ ID NO. 5810, said mutations corresponding to:
- (a) L156H, S172C, F178Y, and E186D, or
- (b) D70N, D74N, D100N, and L156H;
- (vi) one or more mutations relative to SEQ ID NO. 5810, said mutations corresponding to:
- (a) G63D
- (b) G63D and M240L
- G63D, E69V and N231I, or
- T55K, G63N and Q248N;
- and
- (vii) two or more mutations relative to SEQ ID NO. 5810, said two or more mutations corresponding to:
- D72F and V241F, D72F and P249L, D72F and P249F, D72F, V241F and P249L, A77I and P249F, or V241F and P249L;
- and
- b. at least one payload which is operably linked to the SRE, wherein the payload comprises a membrane-associated Interleukin 12 (IL12), wherein the membrane-associated IL 12 is a fusion protein comprising an IL12 subunit beta (p40), an IL12 subunit alpha (p35), at least one linker, and a transmembrane domain,
- wherein the p40 comprises an amino acid sequence selected from SEQ ID NO:
- 4, SEQ ID NO. 5763, or SEQ ID NO. 5774,
- and wherein the p35 comprises an amino acid sequence selected from SEQ ID NO:
- 1, SEQ ID NO. 5777 or SEQ ID NO. 5798.
22 more elements
Dependencies are inferred from the claim text.