IP Library › Granted Patent US 12,188,065
Granted Patent B2
US 12,188,065 · App. 17/042,682 · Granted Jan 7, 2025

Peptides and conjugates

Inventor: Anthony Hollander (Liverpool, GB)
Assignee: THE UNIVERSITY OF LIVERPOOL
C12N9/6491A61K47/50C07K14/47C12Y304/24024
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Quick Facts
Patent No.
US 12,188,065
App. No.
17/042,682
Granted
Jan 7, 2025
Kind
B2
Abstract

Provided are peptides, and conjugates comprising targeting peptides and payloads. The peptides comprise a plurality of modules corresponding to at least one of module 1, module 2, or module 3 of the collagen binding domain of a gelatinase, or a gelatin-binding fragment or variant thereof. The gelatinase may be MMP-2. The conjugates may be therapeutic or non-therapeutic. Medical uses of the peptides or therapeutic conjugates, and pharmaceutical compositions comprising these, are also provided, as are nucleic acids encoding the peptides.

Claims (21)

1. A peptide comprising a plurality of modules corresponding to module 1 of the collagen binding domain of MMP-2, a plurality of modules corresponding to module 2 of the collagen binding domain of MMP-2, or a plurality of modules corresponding to module 3 of the collagen binding domain of MMP-2, wherein module 1 comprises the amino acid sequence set out in SEQ ID NO: 6 or a sequence with at least 90% sequence identity thereto, wherein module 2 comprises the amino acid sequence set out in SEQ ID NO: 11 or a sequence with at least 90% sequence identity thereto, and wherein module 3 comprises the amino acid sequence set out in SEQ ID NO: 17 or a sequence with at least 90% sequence identity thereto.

2. A peptide according to claim 1 , comprising a plurality of modules corresponding to module 2 of the collagen binding domain of MMP-2, wherein module 2 comprises the amino acid sequence set out in SEQ ID NO: 11 or a sequence with at least 90% sequence identity thereto.

3. A peptide according to claim 1 , comprising a total of three modules corresponding to module 2 of the collagen binding domain of MMP-2.

4. A peptide according to claim 1 , comprising a plurality of modules corresponding to module 1 of the collagen binding domain of MMP-2, wherein module 1 comprises the amino acid sequence set out in SEQ ID NO: 6 or a sequence with at least 90% sequence identity thereto.

5. A peptide according to claim 1 , comprising at least one linker sequence flanking at least one module of the collagen binding domain of MMP-2.

6. A peptide according to claim 5 , wherein the at least one linker sequence is selected from the group consisting of: SEQ ID NO: 29, SEQ ID NO: 32, linker sequence 2 consisting of amino acid residues HEA, and linker sequence 3 consisting of amino acid residues ETA.

7. A peptide according to claim 6 , comprising all of said linker sequences.

8. A peptide according to claim 1 , comprising a variant of module 2 of the collagen binding domain of MMP-2 having the amino acid sequence set out in SEQ ID NO: 14.

9. A peptide according to claim 1 , comprising a variant of module 2 of the collagen binding domain of MMP-2 wherein the variant has

at least one amino acid corresponding to residues 19 or 51 of SEQ ID NO: 14 is modified as compared to the corresponding residue of SEQ ID NO: 14.

10. A peptide according to claim 9 comprising a plurality of modules corresponding to module 2 of the collagen binding domain of MMP-2, comprising a sequence set out in SEQ ID NO: 13, or comprising a plurality of modules corresponding to module 2 of the collagen binding domain of MMP-2, comprising a sequence set out in SEQ ID NO: 14, or both.

11. A peptide according claim 1 , wherein the peptide has a binding affinity for type II collagen gelatin that is at least 10-fold higher than the binding affinity of the native CBD of MMP-2.

12. A peptide according to claim 1 , comprising the amino acid sequence set out in SEQ ID NO: 25.

13. A peptide according to claim 12 , consisting of the amino acid sequence set out in SEQ ID NO: 25.

14. A conjugate comprising a targeting peptide and a payload, wherein the targeting peptide comprises a plurality of module 1 of the collagen binding domain of MMP-2, a plurality of module 2 of the collagen binding domain of MMP-2, or a plurality of module 3 of the collagen binding domain of a MMP-2, wherein module 1 comprises the amino acid sequence set out in SEQ ID NO: 6 or a sequence with at least 90% sequence identity thereto, wherein module 2 comprises the amino acid sequence set out in SEQ ID NO: 11 or a sequence with at least 90% sequence identity thereto, and wherein module 3 comprises the amino acid sequence set out in SEQ ID NO: 17 or a sequence with at least 90% sequence identity thereto.

15. A conjugate according to claim 14 , wherein the targeting peptide comprises the amino acid sequence of SEQ ID NO: 25.

16. A conjugate according to claim 14 , wherein the payload comprises a therapeutic payload and the conjugate is a therapeutic conjugate.

17. A therapeutic conjugate according to claim 16 , wherein the therapeutic payload is selected from the group consisting of: a therapeutic cell; a therapeutic drug molecule; and a therapeutic growth factor.

18. A conjugate according to claim 14 , wherein the payload comprises a non-therapeutic payload, and the conjugate is a non-therapeutic conjugate.

19. A non-therapeutic conjugate according to claim 18 , wherein the payload comprises an imaging agent.

20. A method of treating a disorder associated with generation or accumulation of gelatin, comprising administering a peptide according to claim 1 , or conjugate comprising a peptide according to claim 1 and a payload.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 13, 2021
From: HOLLANDER, ANTHONY
To: THE UNIVERSITY OF LIVERPOOL
Reel/Frame 055901/0389 →
Priority Claims (2)
GB 1805306 · Mar 29, 2018 · national
GB 1817486 · Oct 26, 2018 · national
Continuity (1)
Related Publication 20210123036A1 · Apr 29, 2021
References Cited (23)
US 6184021B1 · Senior · 2001 [cited by applicant]
US 10000554B2 · Sekiguchi · 2018 [cited by examiner]
GB 2468757A · 2010 [cited by applicant]
WO WO2007144781A2 · 2007 [cited by examiner]
WO 2003002729A1 · 2009 [cited by applicant]
WO 2012112690A2 · 2012 [cited by applicant]
WO 2017210598A1 · 2017 [cited by applicant]
WO 2019186190A1 · 2019 [cited by applicant]
Obermaier, C., Griebel, A., Westermeier, R. (2015). Principles of Protein Labeling Techniques. In: Posch, A. (eds) Proteomic Profiling. Methods in Molecular Biology, vol. 1295. Humana Press, New York, NY. doi.org/10.100… [cited by examiner]
Xu et al., “Contributions of the MMP-2 collagen binding domain to gelatin cleavage substrate binding via the collagen binding domain is required for hydrolysis of gelatin but not short peptides”, Matrix Biology 23: 171-… [cited by examiner]
Xu et al., NMR Mapping and Functional Confirmation of the Collagen Binding Sites of MMP-2, Biochemistry, 2009, vol. 48(25), pp. 1-21. [cited by applicant]
Trexler et al., Peptide Ligands for the FN2 Modules of Matrix Metalloproteinase 2 (MMP-2), , Journal of Cell Biology, 2002. [cited by applicant]
Briknarova et al., The second type II module from human matrix metalloproteinase 2: structure, function and dynamics, Structure, 1999, vol. 7(10), pp. 1235-1245. [cited by applicant]
Gehrmann et al., Modular Autonomy, Ligand Specificity, and Functional Cooperativity of the Three In-tandem Fibronectin Type II Repeats from Human Matrix Metalloproteinase 2, The Journal of Biological Chemistry, 2004, vo… [cited by applicant]
Gehrmann et al., The Col-1 Module of Human Matrix Metalloproteinase-2 (MMP-2): Structural/Functional Relatedness between Gelatin-Binding Fibronectin Type II Modules and Lysine-Binding Kringle Domains, Biol. Chem., 2002,… [cited by applicant]
GB Search Report for GB1805306.6 dated Nov. 28, 2018, 2 pages. [cited by applicant]
Xu et al., Functional basis for the overlap in ligand interactions and substrate specificities of matrix metalloproteinases-9 and -2, Biochem, J., 2005, vol. 392, pp. 127-134. [cited by applicant]
Steffensen et al., Extracellular Matrix Binding Properties of Recombinant Fibronectin Type II-like Modules of Human 72-kDa Gelatinase/Type IV Collagenase, 1995, vol. 270(19), pp. 11555-11566. [cited by applicant]
International Search Report and Written Opinion for PCT/GB2019/050917 dated Jul. 23, 2019, 17 pages. [cited by applicant]
Mikhailova et al., Identification of collagen binding domain residues that govern catalytic activities of matrix metalloproteinase-2 (MMP-2), Matrix Biology, 2012, vol. 31(7-8), pp. 380-388. [cited by applicant]
Steffensen et al., Human fibronectin and MMP-2 collagen binding domains compete for collagen binding sites and modify cellular activation of MMP-2, Matrix Biology, 2002, vol. 21(5) pp. 399-414. [cited by applicant]
Hollander et al., Damage to type II collagen in aging and osteoarthritis starts at the articular surface, originates around chondrocytes, and extends into the cartilage with progressive degeneration, The Journal of Clin… [cited by applicant]
Zwolanek et al., β1 Integrins Mediate Attachment of Mesenchymal Stem Cells to Cartilge Lesions, BioResearch Open Access, 2015, vol. 4(1), pp. 39-53. [cited by applicant]