Claims for Patent: 10,208,115

Summary for Patent: 10,208,115

Title:	Amino acid sequences that modulate the interaction between cells of the immune system
Abstract:	The present invention relates to amino acid sequences that block the interaction between (a target on) an antigen presenting cell (APC) and (a target on) a T-cell. More particularly, the present invention relates to amino acid sequences that are directed against (as defined herein) a target on an APC (also referred to herein as \"APC target\") or a target on a T-cell (also referred to herein as \"T-cell target\"). The invention further relates to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences.
Inventor(s):	Hermans; Guy (Merelbeke, BE), Verheesen; Peter (Ghent, BE), Dolk; Edward (Utrecht, NL), Hoogenboom; Hendricus Renerus Jacobus Mattheus (Maastricht, NL), Saunders; Michael John Scott (Brussels, BE), De Haard; Hans (Oudelande, NL), de Bruin; Renee (Amsterdam, NL)
Assignee:	Ablynx N.V. (Ghent-Zwijnaarde, BE)
Application Number:	15/050,740
Patent Claims:	1. A polypeptide that binds CTLA4, that essentially consists of 4 framework regions (FR1 to FR4 respectively) and 3 complementarity determining regions (CDR1 to CDR3 respectively) in which: CDR3 is chosen from the group consisting of: the amino acid sequence of SEQ ID NO: 1098 and amino acid sequences that have 3, 2 or 1 amino acid difference with the amino acid sequence of SEQ ID NO: 1098. 2. A polypeptide according to claim 1, that can specifically bind CTLA4 with a dissociation constant (K.sub.D) of 10.sup.-5 to 10.sup.-12 moles/liter or less, 10.sup.-7 to 10.sup.-12 moles/liter or less or 10.sup.-8 to 10.sup.-12 moles/liter. 3. A polypeptide according to claim 1, that essentially consists of a domain antibody, a single domain antibody, VHH, a humanized VHH, or a camelized VH. 4. A polypeptide according to claim 1, that essentially consists of a VHH, a humanized VHH, or a camelized VH that a) has at least 80% amino acid identity with at least one of the amino acid sequences of SEQ ID NOs: 1-22, in which for the purposes of determining the degree of amino acid identity, the amino acid residues that form the CDR sequences are disregarded; and in which: b) one or more of the amino acid residues at positions 11, 37, 44, 45, 47, 83, 84, 103, 104 and 108 according to the Kabat numbering are chosen from at position 11: L, M, S, V, and W; at position 37: F, Y, H, I, L, and V; at position 44: G, E, A, D, Q, R, S, and L; at position 45: L, R, C, I, P, Q, and V; at position 47: W, L, F, A, G, I, M, R, S, V, and Y; at position 83: R, K, N, E, G, I, M, Q, and T; at position 84: P, A, L, R, S, T, D, and V; at position 103: W, P, R, and S; at position 104: G and D; and at position 108: Q, L, and R. 5. A polypeptide according to claim 1, that essentially consists of a VHH, a humanized VHH, or a camelized VH that a) has at least 80% amino acid identity with the amino acid sequence of SEQ ID NO: 1306; in which for the purposes of determining the degree of amino acid identity, the amino acid residues that form the CDR sequences are disregarded; and in which: b) one or more of the amino acid residues at positions 11, 37, 44, 45, 47, 83, 84, 103, 104 and 108 according to the Kabat numbering are chosen from at position 11: L, M, S, V, and W; at position 37: F, Y, H, I, L, and V; at position 44: G, E, A, D, Q, R, S, and L; at position 45: L, R, C, I, P, Q, and V; at position 47: W, L, F, A, G, I, M, R, S, V, and Y; at position 83: R, K, N, E, G, I, M, Q, and T; at position 84: P, A, L, R, S, T, D, and V; at position 103: W, P, R, and S; at position 104: G and D; and at position 108: Q, L, and R. 6. A polypeptide according to claim 1, that essentially consists of a VHH, a humanized VHH, or a camelized VH that a) is a humanized variant of the amino acid sequence of SEQ ID NO: 1306; and/or b) has at least 80% amino acid identity with the amino acid sequence of SEQ ID NO: 1306 and/or at least one of the amino acid sequences of SEQ ID NOs: 1407-1412, in which for the purposes of determining the degree of amino acid identity, the amino acid residues that form the CDR sequences are disregarded; and in which: c) one or more of the amino acid residues at positions 11, 37, 44, 45, 47, 83, 84, 103, 104 and 108 according to the Kabat numbering are chosen from at position 11: L, M, S, V, and W; at position 37: F, Y, H, I, L, and V; at position 44: G, E, A, D, Q, R, S, and L; at position 45: L, R, C, I, P, Q, and V; at position 47: W, L, F, A, G, I, M, R, S, V, and Y; at position 83: R, K, N, E, G, I, M, Q, and T; at position 84: P, A, L, R, S, T, D, and V; at position 103: W, P, R, and S; at position 104: G and D; and at position 108: Q, L, and R. 7. A polypeptide that cross-blocks the binding to CTLA4 by at least one of the polypeptides according to claim 1. 8. A polypeptide that is cross-blocked from binding to CTLA4 by at least one of the polypeptides according to claim 1. 9. A compound or construct, that comprises or essentially consists of one or more polypeptides according to claim 1, and optionally further comprises one or more other groups, residues or moieties or binding units, optionally linked via one or more linkers. 10. A compound or construct according to claim 9, in which said one or more other groups, residues or moieties or binding units are chosen from the group consisting of domain antibodies, single domain antibodies, VHHs, humanized VHHs and camelized VHs. 11. A compound or construct according to claim 9, which is a multivalent or multispecific construct. 12. A compound or construct according to claim 9, in which said one or more other groups, residues, moieties or binding units provide the compound or construct with increased serum half-life, compared to the polypeptide without the one or more other groups, residues moieties or binding units. 13. A compound or construct according to claim 12, in which said one or more other groups, residues, moieties or binding units that provide the compound or construct with increased serum half-life is chosen from the group consisting of serum proteins or fragments thereof, binding units that can bind to serum proteins, an Fc portion, and small proteins or peptides that can bind to serum proteins. 14. A compound or construct according to claim 12, in which said one or more other groups, residues, moieties or binding units that provide the compound or construct with increased serum half-life are selected from the group consisting of human serum albumin and fragments thereof. 15. A compound or construct according to claim 12, in which said one or more other groups, residues, moieties or binding units that provide the compound or construct with increased serum half-life are selected from the group consisting of binding units that can bind to serum albumin, human serum albumin, and a serum immunoglobulin. 16. A compound or construct according to claim 12, in which said one or more other groups, residues, moieties or binding units that provide the compound or construct with increased serum half-life are selected from the group consisting of domain antibodies, single domain antibodies, VHHs, humanized VHHs and camelized VHs, that can bind to serum albumin, human serum albumin, or a serum immunoglobulin. 17. A compound or construct according to claim 12, that has a serum half-life that is at least 1.5 times, at least 2 times, at least 5 times, at least 10 times or more than 20 times, greater than the half-life of the polypeptide without the one or more groups, residues, moieties or binding units. 18. A nucleic acid or nucleotide sequence, that encodes a polypeptide according to claim 1. 19. A composition, comprising at least one polypeptide according to claim 1. 20. A composition according to claim 19, which is a pharmaceutical composition, that further comprises at least one pharmaceutically acceptable carrier, diluent or excipient and/or adjuvant, and that optionally comprises one or more further pharmaceutically active polypeptides and/or compounds. 21. A polypeptide that binds CTLA4, that essentially consists of 4 framework regions (FR1 to FR4 respectively) and 3 complementarity determining regions (CDR1 to CDR3 respectively), in which CDR1 is SEQ ID NO: 682, CDR2 is SEQ ID NO: 890, and CDR3 is SEQ ID NO: 1098. 22. A compound or construct, that comprises or essentially consists of one or more polypeptides according to claim 21, and optionally further comprises one or more other groups, residues or moieties or binding units, optionally linked via one or more linkers. 23. A compound or construct according to claim 22, in which said one or more other groups, residues, moieties or binding units provide the compound or construct with increased serum half-life, compared to the polypeptide without the one or more other groups, residues moieties or binding units. 24. A nucleic acid or nucleotide sequence, that encodes a polypeptide according to claim 21. 25. A composition, comprising at least one polypeptide according to claim 21.

Details for Patent 10,208,115

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		2026-12-15
Baxalta Us Inc.	BUMINATE, FLEXBUMIN	albumin (human)	Injection	101452	03/03/1954		2026-12-15
Csl Behring Ag	ALBURX	albumin (human)	Injection	102366	07/23/1976		2026-12-15
Grifols Biologicals Llc	ALBUTEIN	albumin (human)	Injection	102478	08/15/1978		2026-12-15