IP Library › Granted Patent US 12,110,521

Granted Patent B2

US 12,110,521 · App. 17/749,034 · Granted Oct 8, 2024

Engineered methionine gamma lyase variants

Inventors: Kierra Aleece Franklin (Dolton, IL); Stephanie Sue Galanie (Knoxville, TN); Gjalt W. Huisman (Redwood City, CA); Nikki D. Kruse (San Carlos, CA); Kerryn McCluskie (Pacifica, CA); Vesna Mitchell (Santa Clara, CA); Leann Quertinmont Teadt (Redwood City, CA); Kristen Jean Vallieu (Las Vegas, NV)

Assignee: SYNTIS BIO, INC.

C12N9/88 A61K38/51 A61P3/00 C12N1/205 C12N15/70 C12Y404/01011 C12N2800/101 C12R2001/19

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Quick Facts

Patent No.: US 12,110,521
App. No.: 17/749,034
Filed: May 19, 2022
Granted: Oct 8, 2024
Kind: B2
Examiner: SELWANES, JOHN PAUL
Art Unit: 1657
USPC: 424/94.1

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present invention provides engineered methionine gamma lyase polypeptides and compositions thereof. The engineered methionine gamma lyase polypeptides have been optimized to provide improved thermostability, protease stability, and stability under a range of pH conditions, including acidic (pH<7) conditions. The present invention also relates to the use of the compositions comprising the engineered methionine gamma lyase polypeptides for therapeutic purposes.

Claims (25)

1. A recombinant methionine gamma lyase comprising a polypeptide sequence comprising at least 85% sequence identity to the reference sequence of SEQ ID NO: 1488, wherein the polypeptide sequence comprises at least a substitution 189I/L/M/P/S, 69I/R/W, 237K/A/G/H/L/R/T/Y, 236A/C/R, or 341F, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 2.

2. The recombinant methionine gamma lyase of claim 1 , comprising a polypeptide sequence comprising at least 90%, 91%, 92%, 93%, or 94% sequence identity to the reference sequence of SEQ ID NO: 1488.

3. The recombinant methionine gamma lyase of claim 1 , comprising a polypeptide sequence comprising at least 95%, 96%, 97%, or 98% sequence identity to the reference sequence of SEQ ID NO: 1488.

4. The recombinant methionine gamma lyase of claim 1 , comprising a polypeptide sequence comprising at least 99%, sequence identity to the reference sequence of SEQ ID NO: 1488.

5. The recombinant methionine gamma lyase of claim 1 , wherein the polypeptide sequence of the recombinant methionine gamma lyase comprises at least the substitution 189I/L/M/P/S.

6. The recombinant methionine gamma lyase of claim 1 , wherein the polypeptide sequence of the recombinant methionine gamma lyase comprises at least the substitution 69I/R/W.

7. The recombinant methionine gamma lyase of claim 1 , wherein the polypeptide sequence of the recombinant methionine gamma lyase comprises at least the substitution 237K/A/G/H/L/R/T/Y.

8. The recombinant methionine gamma lyase of claim 7 wherein the polypeptide sequence of the recombinant methionine gamma lyase comprises at least the substitution 237K.

9. The recombinant methionine gamma lyase of claim 1 , wherein the polypeptide sequence of the recombinant methionine gamma lyase comprises at least the substitution 236A/C/R.

10. The recombinant methionine gamma lyase of claim 1 , wherein the polypeptide sequence of the recombinant methionine gamma lyase comprises at least the substitution 341F.

11. The recombinant methionine gamma lyase of claim 1 , wherein the polypeptide sequence of the recombinant methionine gamma lyase comprises at least the substitution 189I/L, 69I/R/W, 237K, 236R, or 341F, or 57Y, or combinations thereof.

12. The recombinant methionine gamma lyase of claim 1 , wherein the polypeptide sequence of the recombinant methionine gamma lyase further comprises at least a substitution at position 8, 11, 23, 55, 141, 165, 173, 219, 223, 263, 267, 276, 279, 283, 290, 298, 304, 334, 344, 366, or 368, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 2.

13. The recombinant methionine gamma lyase of claim 1 , wherein the polypeptide sequence of the recombinant methionine gamma lyase further comprises at least a substitution 8S, 11M, 23K, 55K/S, 141E, 165R, 173V, 219VL, 223I, 263G, 267E, 276I, 279F, 283H, 290A/Q, 298S, 304R, 334L, 344T, 366E, or 368D, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 2.

14. The recombinant methionine gamma lyase of claim 1 , wherein the polypeptide sequence of the recombinant methionine gamma lyase comprises at least a substitution set:

8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233S/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/362E/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233M/236R/237K/263G/267E/276I/279F/283H/290Q/298N/304R/341F/362E/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298N/304R/341F/362E/366E/368D/384G, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D/398G, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298R/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/230V/233Q/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D/384G/395R/398G, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/230V/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/362E/366E/368D/395R, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/230V/233Q/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/308K/341F/366E/368D/384G/395R, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/230V/233M/236R/237K/263G/267E/276I/279F/283H/290Q/298N/301S/304R/341F/366E/368D/395R, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/230V/233M/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D/384G/395R, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233Q/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D/384G/395R, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233S/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D/384G/395R, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233M/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/362E/366E/368D/395R/398G, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/230V/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/230V/233Q/236R/237K/263G/267E/276I/279F/281V/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189M/219L/223I/230V/233S/236R/237K/263G/267E/276I/279F/283H/290Q/298N/304R/341F/366E/368D/395R/398G, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/230V/233Q/236R/237K/263G/267E/276I/279F/283H/290Q/298N/304R/341F/362E/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/230V/233M/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/362E/366E/368D/395R, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233M/236R/237K/263G/267E/276I/279F/283H/290Q/298N/304R/308K/341F/366E/368D/384G/395R, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233S/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/362E/366E/368D/395R, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298Y/301S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233M/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D/384G/398G, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D/395R/398G, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298N/301S/304R/308K/341F/366E/368D/384G, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233Q/236R/237K/263G/267E/276I/279F/283H/290Q/298R/304R/341F/362E/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/230V/233Q/236R/237K/263G/267E/276I/279F/283H/290Q/298R/301S/304R/341F/362E/366E/368D/384G/395R, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/230V/233S/236R/237K/263G/267E/276I/279F/283H/290Q/298N/301S/304R/341F/362E/366E/368D/384G/395R, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/362E/366E/368D/384G, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233Q/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233G/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D/395R, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233Q/236R/237K/263G/267E/276I/279F/283H/290Q/298N/301S/304R/341F/362E/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/230V/233Q/236R/237K/263G/267E/276I/279F/283H/290Q/298R/301S/304R/341F/366E/368D/395R, or 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/230V/233Q/236R/237K/263G/267E/276I/279F/283H/290Q/298N/301S/304R/341F/366E/368D/395R, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 2.

15. The recombinant methionine gamma lyase of claim 1 , wherein the polypeptide sequence of the recombinant methionine gamma lyase comprises at least a substitution set 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/220I/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189P/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/93L/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189S/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/221G/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/155F/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/230V/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/63G/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/284V/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/308K/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/284E/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/229G/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/284S/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/199W/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/362E/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/308S/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/301G/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/300R/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298R/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D/395R, 8S/11M/23K/55S/57Y/69I/126R/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69V/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D/395A, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233Q/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D/384G, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233V/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/323S/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D/396Q, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298G/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/282Q/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/254A/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/175V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/365R/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D/396R, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/308L/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D/398G, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298C/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141V/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/253G/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 6P/8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233G/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D/384Q, 8S/11M/23K/55S/57Y/69I/82C/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233S/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304K/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/233M/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/9R/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/301S/304R/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304V/341F/366E/368D, 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298N/304R/341F/366E/368D, or 8S/11M/23K/55S/57Y/69I/141E/165R/173V/189L/219L/223I/236R/237K/263G/267E/276I/279F/283H/290Q/298S/304R/341F/366E/368D/384A, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 2.

16. The recombinant methionine gamma lyase of claim 1 , wherein the polypeptide sequence of the recombinant methionine gamma lyase comprises SEQ ID NO: 4, 6, 8, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 34, 36, 38, 40, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 94, 96, 158, 208, 210, 212, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 234, 236, 238, 240, 242, 244, 246, 248, 250, 252, 254, 256, 258, 260, 262, 264, 266, 268, 270, 272, 274, 276, 278, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, 302, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 326, 328, 330, 332, 334, 336, 338, 340, 342, 344, 346, 348, 350, 352, 354, 356, 358, 360, 362, 364, 366, 368, 370, 372, 374, 376, 378, 380, 382, 384, 386, 388, 390, 392, 394, 396, 398, 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456, 458, 460, 462, 464, 466, 470, 468, 472, 474, 476, 478, 480, 482, 484, 486, 488, 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, 556, 558, 560, 562, 564, 566, 568, 570, 572, 574, 576, 578, 580, 582, 584, 586, 588, 590, 592, 594, 596, 598, 600, 602, 604, 606, 608, 610, 612, 614, 616, 618, 620, 622, 624, 626, 628, 630, 632, 634, 636, 638, 640, 642, 644, 648, 650, 652, 654, 658, 660, 662, 664, 666, 668, 670, 672, 674, 676, 678, 680, 682, 684, 686, 688, 690, 692, 694, 696, 698, 700, 702, 704, 706, 708, 710, 712, 714, 716, 718, 720, 722, 724, 726, 728, 730, 732, 734, 736, 738, 740, 742, 744, 746, 748, 750, 752, 754, 756, 758, 760, 762, 764, 766, 768, 770, 772, 774, 776, 778, 780, 782, 784, 786, 788, 790, 792, 794, 796, 798, 800, 802, 804, 806, 808, 810, 812, 814, 816, 818, 820, 822, 824, 826, 828, 830, 832, 834, 836, 838, 840, 842, 844, 846, 848, 850, 852, 854, 856, 858, 860, 862, 864, 866, 868, 870, 872, 874, 876, or 878.

17. The recombinant methionine gamma lyase of claim 1 , wherein the polypeptide sequence of the recombinant methionine gamma lyase comprises SEQ ID NO: 880, 882, 884, 886, 888, 890, 892, 894, 896, 898, 900, 902, 904, 906, 908, 910, 912, 914, 916, 918, 920, 922, 924, 926, 928, 930, 932, 934, 936, 938, 940, 942, 944, 946, 948, 950, 952, 954, 956, 958, 960, 962, 964, 966, 968, 970, 972, 974, 976, 978, 980, 982, 984, 986, 988, 990, 992, 994, 996, 998, 900, 902, 904, 906, 908, 910, 912, 914, 916, 918, 920, 922, 924, 926, 928, 930, 932, 934, 936, 938, 940, 942, 944, 946, 948, 950, 952, 954, 956, 958, 960, 962, 964, 966, 968, 970, 972, 974, 976, 978, 980, 982, 984, 986, 988, 990, 992, 994, 996, 998, 1000, 1002, 1004, 1006, 1008, 1010, 1012, 1014, 1016, 1018, 1020, 1022, 1024, 1026, 1028, 1030, 1032, 1034, 1036, 1038, 1040, 1042, 1044, 1046, 1048, 1050, 1052, 1054, 1056, 1058, 1060, 1062, 1064, 1066, 1068, 1070, 1072, 1074, 1076, 1078, 1080, 1082, 1084, 1086, 1088, 1090, 1092, 1094, 1096, 1098, 1100, 1102, 1104, 1106, 1108, 1110, 1112, 1114, 1116, 1118, 1120, 1122, 1124, 1126, 1128, 1130, 1132, 1134, 1136, 1138, 1140, 1142, 1144, 1146, 1148, 1150, 1152, 1154, 1156, 1158, 1160, 1162, 1164, 1166, 1168, 1170, 1172, 1174, 1176, 1178, 1180, 1182, 1184, 1186, 1188, 1190, 1192, 1194, 1196, 1198, 1200, 1202, 1204, 1206, 1208, 1210, 1212, 1214, 1216, 1218, 1220, 1222, 1224, 1226, 1228, 1230, 1232, 1234, 1236, 1238, 1240, 1242, 1244, 1246, 1248, 1250, 1252, 1254, 1256, 1258, 1260, 1262, 1264, 1266, 1268, 1270, 1272, 1274, 1276, 1278, 1280, 1282, 1284, or 1286.

18. The recombinant methionine gamma lyase of claim 1 , wherein the polypeptide sequence of the recombinant methionine gamma lyase comprises SEQ ID NO: 1288, 1290, 1292, 1294, 1296, 1298, 1310, 1312, 1314, 1316, 1318, 1320, 1322, 1324, 1326, 1328, 1330, 1332, 1334, 1336, 1338, 1340, 1342, 1344, 1346, 1348, 1350, 1352, 1354, 1356, 1358, 1360, 1362, 1364, 1366, 1368, 1370, 1372, 1374, 1376, 1378, 1380, 1382, 1384, 1386, 1388, 1390, 1392, 1394, 1396, 1398, 1400, 1402, 1404, 1406, 1408, 1410, 1412, 1414, 1416, 1418, 1420, 1422, 1424, 1426, 1428, 1430, 1432, 1434, 1436, 1438, 1440, 1442, 1444, 1446, 1448, 1450, 1452, 1454, 1456, 1458, 1460, 1462, 1464, 1466, 1468, 1470, 1472, 1474, 1476, 1478, 1480, 1482, 1484, 1486, 1488, 1490, 1492, 1494, 1496, 1498, 1500, 1502, 1504, 1506, 1508, 1510, 1512, 1514, 1516, 1518, 1520, 1522, 1524, 1526, 1528, 1530, 1532, 1534, 1536, 1538, 1540, 1542, 1544, 1546, 1548, 1550, 1552, 1554, 1556, 1558, 1560, 1562, 1564, 1566, 1568, 1570, 1572, 1574, 1576, 1578, 1580, 1582, 1584, 1586, 1588, 1590, 1592, 1594, 1596, 1598, 1600, 1602, 1604, 1606, 1608, 1610, 1612, 1614, 1616, 1618, 1620, 1622, 1624, 1626, 1628, 1630, 1632, 1634, 1636, 1638, 1640, 1642, 1644, 1646, 1648, 1650, 1652, 1654, 1656, 1658, 1660, 1662, 1664, 1666, 1668, 1670, 1672, 1674, 1676, 1678, 1680, 1682, 1684, 1686, 1688, 1690, 1692, 1694, 1696, 1698, 1700, 1702, 1704, 1706, 1708, 1710, 1712, 1714, 1716, 1718, 1720, 1722, 1724, 1726, 1728, 1730, 1732, or 1734.

19. The recombinant methionine gamma lyase of claim 1 , wherein the recombinant methionine gamma lyase exhibits at least one improved property selected from: i) enhanced catalytic activity; ii) increased tolerance to acid pH; iii) increased thermotolerance; iv) increased tolerance to pH 5.2; v) increased tolerance to at least one protease; and vi) increased activity in the presence of substrate concentration of 0.25 mM methionine; or a combination of any of i), ii), iii), iv), v), and vi), as compared to a reference methionine gamma lyase having the sequence of SEQ ID NO: 2.

20. A composition comprising a recombinant methionine gamma lyase of claim 1 .

21. A pharmaceutical composition comprising a recombinant methionine gamma lyase of claim 1 .

22. The pharmaceutical composition of claim 21 , further comprising a pharmaceutically acceptable carrier and/or excipient.

23. The pharmaceutical composition of claim 21 , wherein the composition is suitable for oral administration to a human.

24. The recombinant methionine gamma lyase of claim 1 , wherein the polypeptide sequence of the recombinant methionine gamma lyase comprises SEQ ID NO: 94, 248, 352, 478, 832, 916, 1172, 1232, 1346, 1488 or 1706.

Assignments (5)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 10, 2025

From: CODEXIS, INC.

To: SYNTIS BIO, INC.

Reel/Frame 073080/0487 →

RELEASE OF SECURITY INTEREST Recorded Aug 21, 2024

From: INNOVATUS LIFE SCIENCES LENDING FUND I, LP, AS COLLATERAL AGENT

To: CODEXIS, INC.

Reel/Frame 068361/0757 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 17, 2024

From: FRANKLIN, KIERRA ALEECE; GALANIE, STEPHANIE SUE; HUISMAN, GJALT W.; KRUSE, NIKKI D.; MCCLUSKIE, KERRYN; MITCHELL, VESNA; TEADT, LEANN QUERTINMONT; VALLIEU, KRISTEN JEAN

To: CODEXIS, INC.

Reel/Frame 067749/0799 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 7, 2024

From: CODEXIS, INC.

To: SYNTIS BIO, INC.

Reel/Frame 067340/0445 →

SECURITY INTEREST Recorded Feb 15, 2024

From: CODEXIS, INC.

To: INNOVATUS LIFE SCIENCES LENDING FUND I, LP, AS COLLATERAL AGENT

Reel/Frame 066600/0650 →

Continuity (3)

Provisional Application 63274349 · Nov 1, 2021

Provisional Application 63191799 · May 21, 2021

Related Publication 20220403362A1 · Dec 22, 2022