Bcl-2-modifying factor (bmf) sequences and their use in...

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

Reexamination Certificate

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Reexamination Certificate

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07572900

ABSTRACT:
The present invention relates generally to novel molecules capable of, inter alia, modulating apoptosis in mammalian cells and to genetic sequences encoding same. More particularly, the present invention relates to a novel member of the Bcl-2 family of proteins, referred to herein as “Bmf”, and to genetic sequences encoding same and to regulatory sequences such as a promoter sequence directing expression of Bmf. Bmf comprises a BH3 domain which facilitates interaction to pro-survival Bcl-2 family members thereby triggering apoptosis. Bmf is regarded, therefore, as a BH3-only molecule. The molecules of the present invention are useful, for example, in therapy, diagnosis, antibody generation and as a screening tool for therapeutic agents capable of modulating physiological cell death or survival and/or modulating cell cycle entry. The present invention further contemplates genetically modified animals in which one or both alleles of Bmf are mutated or partially or wholly deleted alone or in combination with a mutation in one or both alleles of another Bcl-2-type molecule such as but not limited to Bim. The genetically modified animals are useful inter alia in screening for agents which ameliorate the symptoms of diseases caused by defects in apoptosis or which specifically promote apoptosis of target cells.

REFERENCES:
Yuan, S-M., et al. 1998 Proteins 30: 136-143.
Sergel, T.A., et al. 2000 Journal of Virology 74(11): 5101-5107.
Seffernick, J.L., et al. 2001 Journal of Bacteriology 183(8): 2405-2410.
H. Puthalakath, et al., “Bmf: A Proapoptotic BH3-Only Protein Regulated by Interaction with the Myosin V Actin Motor Complex, Activated by Anoikis”,Science, vol. 293, pp. 1829-1832, (Sep. 2001).
EMBL Database Accession No. AK024472.Homo sapiensmRNA for FLJ00065 protein. Sep. 29, 2000. & GenPept database No. BAB15762. See whole document, the sequence shows 100% homology with SEQ ID No. 4, 6 and 8 and 87% homology with SEQ ID No. 2.
EMBL Database Accession No. AC025429.Homo sapienschromosome 15 clone CTD-2006D8 map 15q14. Mar. 15, 2000. See whole document, the sequence shows 100% homology with SEQ ID No. 4, 6 and 8 and 87% homology with SEQ ID No. 2.
GenBank Database Accession Nos. AY029253, AY029254 and GenPept database Accession Nos. AAK38747 and AAK38748, respectively. See whole document, Mus musculus Bmf sequences are 100% identical to SEQ ID Nos. 1, 2, 5-8 andHomo sapiensBMF sequences are 100% identical to SEQ ID Nos. 3-8.
GenBank Database Accession No. AF506761. Rattus norvegicus Bcl-2 modifying factor (Bmf), mRNA. May 16, 2002 and GenPept Database Accession No. AAM28890. See whole document, sequence is up to 96% identical to SEQ ID Nos. 1-8.

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