CD71 binding fibronectin type III domains
The present disclosure relates to polypeptides, such as fibronectin type III (FN3) domains that can bind CD71, their conjugates, isolated nucleotides encoding the molecules, vectors, host-cells, as well as methods of making and using the same.
1. A polypeptide comprising the amino acid sequence that is at least 90% identical to the amino acid sequence selected from the group consisting of SEQ ID NOs: 33-39, 41-62, 81-136, 138-186, 188-261, and 263-309, or at least 91% identical to the amino acid sequence selected from the group consisting of SEQ ID NOs: 40, 137, 187, and 262, or any combination thereof.
2. The polypeptide of claim 1 , wherein the polypeptide comprises two amino acid sequences selected from the group consisting of SEQ ID NOs: 33-62 and 81-309.
3. The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 33-62 and or 81-309.
4. The polypeptide of claim 1 , wherein the polypeptide is conjugated to a detectable label, an oligonucleotide, a therapeutic agent, or any combination thereof.
5. The polypeptide of claim 4 , wherein the detectable label is a radioactive isotope, magnetic beads, metallic beads, colloidal particles, a fluorescent dye, an electron-dense reagent, an enzyme, biotin, digoxigenin, or hapten.
6. The polypeptide of claim 4 , wherein the therapeutic agent is auristatin, monomethyl auristatin phenylalanine, dolostatin, a chemotherapeutic agent, a drug, a growth inhibitory agent, a toxin, or a radioactive isotope.
7. The polypeptide of claim 4 , wherein the therapeutic agent is a chemotherapeutic agent, a drug, an antibody, a growth inhibitory agent, a toxin, a radioactive isotope, an anti-tubulin agent, a polynucleotide, a double stranded short interfering ribonucleic acid (siRNA) molecule or a sense or an antisense strand thereof, a double stranded antisense molecule or a strand thereof, a RNA molecule, a deoxyribonucleic acid (DNA) molecule, DNA minor groove binders, DNA replication inhibitors, alkylating agents, antibiotics, antifolates, antimetabolites, chemotherapy sensitizers, topoisomerase inhibitors, or a vinca alkaloid.
8. The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence that is at least 90% identical to SEQ ID NO: 140.
9. The polypeptide of claim 8 , wherein the polypeptide is conjugated to a detectable label, an oligonucleotide, a therapeutic agent, or any combination thereof.
10. The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence that is at least 95% identical to SEQ ID NO: 140.
11. The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence that is at least 90% identical to SEQ ID NO: 146.
12. The polypeptide of claim 11 , wherein the polypeptide is conjugated to a detectable label, an oligonucleotide, a therapeutic agent, or any combination thereof.
13. The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence that is at least 95% identical to SEQ ID NO: 146.
14. The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence that is at least 90% identical to SEQ ID NO: 179.
15. The polypeptide of claim 14 , wherein the polypeptide is conjugated to a detectable label, an oligonucleotide, a therapeutic agent, or any combination thereof.
16. The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence that is at least 95% identical to SEQ ID NO: 179.
17. The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence that is at least 90% identical to SEQ ID NO: 182.
18. The polypeptide of claim 17 , wherein the polypeptide is conjugated to a detectable label, an oligonucleotide, a therapeutic agent, or any combination thereof.
19. The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence that is at least 95% identical to SEQ ID NO: 182.
20. A pharmaceutical composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable carrier.
21. A pharmaceutical composition comprising the polypeptide of claim 8 and a pharmaceutically acceptable carrier.
22. A pharmaceutical composition comprising the polypeptide of claim 10 and a pharmaceutically acceptable carrier.
23. A pharmaceutical composition comprising the polypeptide of claim 11 and a pharmaceutically acceptable carrier.
24. A pharmaceutical composition comprising the polypeptide of claim 13 and a pharmaceutically acceptable carrier.
25. A pharmaceutical composition comprising the polypeptide of claim 14 and a pharmaceutically acceptable carrier.
26. A pharmaceutical composition comprising the polypeptide of claim 16 and a pharmaceutically acceptable carrier.
27. A pharmaceutical composition comprising the polypeptide of claim 17 and a pharmaceutically acceptable carrier.
28. A pharmaceutical composition comprising the polypeptide of claim 19 and a pharmaceutically acceptable carrier.
29. A method of delivering an agent of interest to a cluster of differentiation 71 (CD71) positive cell, wherein the method comprises contacting the cell with a conjugate comprising the agent of interest coupled to a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 33-62 and 81-309.
30. The method of claim 29 , wherein the cell is a muscle cell a brain cell, or a cell inside of the blood brain barrier.
31. A method of delivering an agent of interest to a CD71 positive cell, wherein the method comprises contacting the cell with a pharmaceutical composition comprising:
a conjugate comprising the agent of interest coupled to the polypeptide of claim 8 ; and
a pharmaceutically acceptable carrier.
32. A method of delivering an agent of interest to a CD71 positive cell, wherein the method comprises contacting the cell with a pharmaceutical composition comprising:
a conjugate comprising the agent of interest coupled to the polypeptide of claim 11 ; and
a pharmaceutically acceptable carrier.
33. A method of delivering an agent of interest to a CD71 positive cell, wherein the method comprises contacting the cell with a pharmaceutical composition comprising:
a conjugate comprising the agent of interest coupled to the polypeptide of claim 14 ; and
a pharmaceutically acceptable carrier.
34. A method of delivering an agent of interest to a CD71 positive cell, wherein the method comprises contacting the cell with a pharmaceutical composition comprising:
a conjugate comprising the agent of interest coupled to the polypeptide of claim 17 ; and
a pharmaceutically acceptable carrier.