Hcmv entry inhibitors
AssigneeAicuris Anti-Infective Cures GmbH
InventorsChristian SINZGER, Cora STEGMANN, Kerstin LAIB SAMPAIO, Barbara ADLER
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Abstract
Subject matter of the present invention is a soluble PDGFR-alpha-Fc chimera or a PDGFR-alpha derived peptide or an anti-PDGFR-alpha antibody or a PDGFR-alpha antibody fragment or anti-PDGFR-alpha non-Ig scaffold for inhibiting HCMV entry for use in a method of treatment in a subject that has been infected by HCMV or for use in a method of prophylaxis of HCMV infection in a subject that has not yet been infected by HCMV.
Claims14
Soluble PDGFR-alpha-Fc chimera for use in a method of treatment in a subject that has been infected by HCMV or for use in a method of prophylaxis of HCMV infection in a subject that has not yet been infected by HCMV, wherein said soluble PDGFR-alpha-Fc chimera comprises a PDGFR-alpha sequence selected from the group comprising:
- I. SEQ ID No. 2 consisting of amino acids 24 to amino acids 524 of SEQ ID No. 1:
- QLSLPSILPNENEKVVQLNSSFSLRCFGESEVSWQYPMSEEESSDVEIRN
- EENNSGLFVTVLEVSSASAAHTGLYTCYYNHTQTEENELEGRHIYIYVPD
- PDVAFVPLGMTDYLVIVEDDDSAIIPCRTTDPETPVTLHNSEGVVPASYD
- SRQGFNGTFTVGPYICEATVKGKKFQTIPFNVYALKATSELDLEMEALKT
- VYKSGETIVVTCAVFNNEVVDLQWTYPGEVKGKGITMLEEIKVPSIKLVY
- TLTVPEATVKDSGDYECAARQATREVKEMKKVTISVHEKGFIEIKPTFSQ
- LEAVNLHEVKHFVVEVRAYPPPRISWLKNNLTLIENLTEITTDVEKIQDR
- YRSKLKLIRAKEEDSGHYTIVAQNEDAVKSYTFELLTQVPSSILDLVDDH
- HGSTGGQTVRCTAEGTPLPDIEWMICKDIKKCNNETSWTILANNVSNIIT
- EIFISRDRSTVEGRVTFAKVEETIAVRCLAKNLLGAENRELKLVAPTLRS
- E,
- II. a sequence having 90% or more identity to SEQ ID No. 2,
- III. a sequence that is a truncated sequence of SEQ ID No. 2 with at least 45 amino acids or a sequence having 90% or more identity to said truncated SEQ ID No. 2,
- IV. variants of sequences according to items I., II., III. having substitutions at one or more of the following positions (numbering adhered to SEQ ID. No. 1):
- Ile-30, Glu-52, Ser-66, Ser-67, Asp-68, Leu-80, Ser-89, His-162, Pro-169, Asp-173, Ile-188, Val-193, Lys-194, Glu-213, Lys-304, Thr-320, His-334, Arg-340, Ile-373, Lys-378, Ala-396, Ala-401, Thr-436, Thr-440, Ile-453, Val-469, Ile-476, Ser-478, Asp-480, Ser-482, Arg-487.
Soluble PDGFR-alpha-Fc chimera is used that is suitable for inhibiting HCMV entry in a method of treatment in a subject that has been infected by HCMV or used for prophylaxis of HCMV infection in a method of treatment of a subject that has not yet been infected by HCMV according the invention wherein said soluble PDGFR-alpha-Fc chimera has at least one of the following mutations or deletions within SEQ ID No. 2 (numbering is adhered to SEQ ID No. 1):
- i) Deletion of amino acids M133-I139;
- ii) Deletion of amino acids V184-G185;
- iii) Deletion of amino acids N204-Y206;
- iv) Deletion of amino acids T259-E262;
- v) Deletion of amino acids Q294-E298;
- vi) SEQ ID No. 2 having at least one point mutation in at least one of the protein regions as specified above under items i., ii., iii., iv., or v.
PDGFR-alpha peptide fragment for use in a method of treatment in a subject that has been infected by HCMV or for use in a method of prophylaxis of HCMV infection in a subject that has not yet been infected by HCMV, wherein said peptide fragment is selected from a group comprising:
- I. SEQ ID No. 9;
- II. SEQ ID No. 10;
- III. SEQ ID No. 11;
- IV. SEQ ID No. 12;
- V. SEQ ID No. 13,
- VI. a peptide fragment of SEQ ID No. 9, SEQ ID No. 10, SEQ ID NO:
- 11, SEQ ID No. 12, or SEQ ID No. 13, any of them having at least 10 amino acids, and
- VII. a variant of the above items I. to VI that exhibits at least 80% sequence identity to the peptide having the sequence of SEQ ID No. 9 or SEQ ID No. 10 or SEQ ID No. 11 or SEQ ID No. 12 or SEQ ID No. 13 that exhibits at least 80% sequence identity to the peptide fragment of SEQ ID No. 9 or SEQ ID No. 10 or SEQ ID No. 11 or SEQ ID No. 12 or SEQ ID No. 13, said variant having a length of at least 10 amino acids.
Anti-PDGFR-alpha antibody or a PDGFR-alpha antibody fragment or anti-PDGFR-alpha non-Ig scaffold binding to the HCMV binding region of PDGFR-alpha as defined in SEQ ID No. 4.
Dependencies are inferred from the claim text.