Claims for Patent: 10,167,322

Summary for Patent: 10,167,322

Title:	Engineered albumin binding polypeptide
Abstract:	The present disclosure relates to a class of engineered polypeptides having a binding affinity for albumin. In particular, the present invention relates to albumin binding polypeptides which have a high resistance to proteolytic cleavage and therapeutic use thereof. The disclosure provides an albumin binding polypeptide comprising an albumin binding motif, which motif consists of the amino acid sequence TABLE-US-00001 (SEQ ID NO. 1782) GX.sub.ASDX.sub.5YKX.sub.8X.sub.9I X.sub.11X.sub.12AX.sub.14TVEGVX.sub.20 ALX.sub.23X.sub.24X.sub.25ILX.sub.28X.sub.29X.sub.B.
Inventor(s):	Ekblad; Caroline (Saltsjo-Boo, SE), Frejd; Fredrik (Stockholm, SE), Lindgren; Joel (Stockholm, SE), Eriksson Karlstrom; Amelie (Bromma, SE)
Assignee:	AFFIBODY AB (Solna, SE)
Application Number:	15/104,070
Patent Claims:	1. An albumin binding polypeptide comprising an albumin binding motif [ABM], which motif consists of the amino acid sequence TABLE-US-00009 (SEQ ID NO: 1782) GX.sub.ASDX.sub.5YKX.sub.8X.sub.9I X.sub.11X.sub.12AX.sub.14TVEGVX.sub.20 ALX.sub.23X.sub.24X.sub.25ILX.sub.28X.sub.29X.sub.BX31 wherein, independently from each other, X.sub.A is selected from C and optionally functionalized K; X.sub.B is selected from C and optionally functionalized K; and X.sub.5 is selected from F and Y; X.sub.8 is selected from D, K, N, R and S; X.sub.9 is selected from F, I, L, M, V and Y; X.sub.11 is selected from D, E, N and S; X.sub.12 is selected from K, N and R; X.sub.14 is selected from K and R; X.sub.20 is selected from D, E, H, K, N, Q, R and S; X.sub.23 is selected from I, K and T; X.sub.24 is selected from A, D, E, G, H, L, S and T; X.sub.25 is selected from A, D, E and H; X.sub.28 is selected from A and K; X.sub.29 is selected from A, E and S; and X.sub.31 is P or is absent; and wherein the amino acid sequence optionally contains an intramolecular crosslink. 2. The albumin binding polypeptide according to claim 1, wherein X.sub.A is C and X.sub.B is K. 3. The albumin binding polypeptide according to claim 1, wherein X.sub.A is C and X.sub.B is C. 4. The albumin binding polypeptide according to claim 1, wherein X.sub.31 is absent. 5. The albumin binding polypeptide according to claim 1, wherein X.sub.31 is P. 6. The albumin binding polypeptide according to claim 1, in which the [ABM] consists of position 16 to position 45 in the amino acid sequence selected from the group consisting of SEQ ID NO:1-1768. 7. The albumin binding polypeptide according to claim 1, in which said albumin binding motif forms part of a three-helix bundle protein domain. 8. The albumin binding polypeptide according to claim 7, in which said three-helix bundle protein domain is selected from the group consisting of domain GA1, domain GA2 and domain GA3 of protein G from Streptococcus strain G148. 9. The albumin binding polypeptide according to claim 7, which comprises the amino acid sequence: LAX.sub.aAKX.sub.bX.sub.cAX.sub.dX.sub.eELX.sub.fX.sub.gY-[ABM] (SEQ ID NO. 1783) wherein [ABM] is an albumin binding motif as defined in claim 1, and, independently of each other, X.sub.a is selected from C, E, Q and S; X.sub.b is selected from C, E, S and V; X.sub.c is selected from A, D, E, L and S; X.sub.d is selected from I, N and L; X.sub.e is selected from A, K, R and S; X.sub.f is selected from D and K; and X.sub.g is selected from A, C, K and S. 10. The albumin binding polypeptide according to claim 1, which comprises the amino acid sequence selected from the group consisting of SEQ ID NO:1-1768. 11. The albumin binding polypeptide according to claim 1, wherein N.sub.A is K or X.sub.B is K, and the K is functionalized. 12. The albumin binding polypeptide according to claim 1, wherein said amino acid sequence is crosslinked. 13. The albumin binding polypeptide according to claim 12, wherein said crosslink extends between the amino acid residue in position X.sub.A and the amino acid residue in position X.sub.B. 14. The albumin binding polypeptide according to claim 12, wherein said polypeptide is resistant to proteolytic cleavage by at least one protease of the gastrointestinal tract. 15. The albumin binding polypeptide according to claim 1, which binds to albumin such that the K.sub.D value of the interaction is at most 1.times.10.sup.-8 M. 16. The albumin binding polypeptide according to claim 1, wherein said albumin is human serum albumin. 17. A compound comprising: at least one moiety (I) which is an albumin binding polypeptide according to claim 1; one moiety (II) which confers a desired therapeutic activity; and optionally, at least one further moiety (III) which confers a desired therapeutic activity, which activity may be the same or different from said activity of moiety (II). 18. A pharmaceutical composition, comprising a compound according to claim 17 and at least one pharmaceutically acceptable excipient. 19. The pharmaceutical composition according to claim 18, which further comprises at least one component for increasing oral bioavailability of said therapeutic activity.

Details for Patent 10,167,322

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Grifols Therapeutics Llc	ALBUKED, PLASBUMIN-20, PLASBUMIN-25, PLASBUMIN-5	albumin (human)	For Injection	101138	10/21/1942		2033-12-20
Baxalta Us Inc.	BUMINATE, FLEXBUMIN	albumin (human)	Injection	101452	03/03/1954		2033-12-20
Csl Behring Ag	ALBURX	albumin (human)	Injection	102366	07/23/1976		2033-12-20
Grifols Biologicals Llc	ALBUTEIN	albumin (human)	Injection	102478	08/15/1978		2033-12-20
Instituto Grifols, S.a.	HUMAN ALBUMIN GRIFOLS	albumin (human)	Injection	103352	02/17/1995		2033-12-20