WO2003015814A1 - New peptides and use thereof in therapeutic agents against feline fiv infection - Google Patents
New peptides and use thereof in therapeutic agents against feline fiv infection Download PDFInfo
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- WO2003015814A1 WO2003015814A1 PCT/US2002/026247 US0226247W WO03015814A1 WO 2003015814 A1 WO2003015814 A1 WO 2003015814A1 US 0226247 W US0226247 W US 0226247W WO 03015814 A1 WO03015814 A1 WO 03015814A1
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- gin
- asn
- glu
- leu
- lys
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
- C12N2740/15022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
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- Proteomics, Peptides & Aminoacids (AREA)
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- Communicable Diseases (AREA)
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- Genetics & Genomics (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention provides novel peptides comprising at least 25 and at most 40 consecutive amino acids selected from the regions 649-696 and 729-782 of the gp36 protein of a FIV strain, or to a corresponding consensus sequence. The peptides of the invention also include analogs wherein K is replaced with R and/or R is replaced with K at on or more positions.
Description
New Peptides and Use Thereof as Therapeutics Against Feline FIV Infection.
RELATED APPLICATIONS
[0001] This application claims priority to French Application No. FR 0110910 filed August 17, 2001 and French Application No.FR 0115424 filed November 29, 2001. The contents of both applications are herein incorporate by reference in their entirety.
FIELD OF THE INVENTION
[0002] The present invention relates the identification and design of new peptides and their therapeutic agent used as therapeutic agents against feline infection with the feline immunodeficiency virus (FIV).
DESCRIPTION OF RELATED ART
[0003] Since the recognition of human acquired immunodeficiency syndrome (AIDS) in 1981 , there has been intensive research into the causal virus, human immunodeficiency virus (HIV), formerly known as human T-cell lymphotropic virus type III (HTLV-III) or lymphadenopathy- associated virus (LAV). It is now known that HIV-specific antibodies are present in the sera not only of most patients with AIDS or AIDS-related complex, but also in the sera of asymptomatic individuals exposed to the virus.
[0004] More recently, a variant virus, known as HIV-2, has also been found to be capable of causing AIDS. Immunoassay methods, such as ELISA, utilizing various polypeptides encoded by the HIV virus have been extensively used in diagnosis and screening. In most cases the polypeptides are either directly prepared from viral material, or are derived from in vitro expression systems using recombinant DNA technology, although such materials are not ideal. Material derived from viral
preparations may be contaminated by viable virus, thus posing a hazard to personnel using the material. Recombinant-derived material may be contaminated by non-HIV protein, resulting in possible loss of specificity.
[0005] Feline immunodeficiency virus (FIV), formerly called feline T lymphotropic lentivirus (Pederson et al., Science, 235:790 (1987)), has been identified in the United States, the United Kingdom (Harbour et al., Vet Rec, 122:84 (1988)), Japan (ishida et al., Jpn J Vet Sci, 50:39 (1988)), Australia (Sabine et al., Aust Vet Practit, 18:105 (1988)), and New Zealand (Swinney et al., NZ Vet J, 37:41 (1989)). The virus appears to be spread by horizontal transmission, predominantly by bite wounds (Yamamoto et al., Am. J. Vet. Res., 8:1246 (1988); Friend et al., Aust. Vet J., 67:237 (1990). FIV has been classified as a member of the subfamily Lentivirinae in the family Retroviridae. This is the family that includes human and simian immunodeficiency viruses, equine infectious anemia, maedi visna of sheep and caprine-arthritis encephalitis viruses (CAEV).
[0006] Cloning and sequencing of FIV has confirmed it to be a lentivirus by its genomic organization and antigenic similarity of its core proteins to those of visna virus and CAEV (Olmsted et al., Proc. Natl. Acad. Sci. USA, 86:2448 (1989); Talbott et al., Proc. Natl. Acad. Sci. USA, 86:5743 (1989); Dow et al., Journal Of Acquired Immune Deficiency Syndromes, 3:658 (1990).
[0007] Feline immunodeficiency is due to a lentivirus, feline immunodeficiency virus (FIV), which exhibits a genetic structure which is similar to that of the lentiviruses of primates (HIV and SIV). Feline immunodeficiency poses a considerable problem for veterinary health in as much as a substantial number of cats infected with FIV have been detected in the United States, in Japan and in Europe (5 to 30% of animals).
[0008] Several independent viral isolates have been prepared across the world, and a certain number of studies have been carried out in order to demonstrate the structure of the isolated strains, in particular as regards the American strain Petaluma [R. L. TALBOTT et al. (Natl. Acad. Sci. USA, 1989, 86, 5743-5747; T. R. PHILIPPS et al. (J. Virol., 1990, 64, 10, 4605- 4613)], the Japanese strains (the TM1 and TM2 strains) [T. MIYAZAWA et al. (Arch. Virol., 1989, 108, 59-68)] or the Swiss isolates (FIVZ1 and FIVZ2) [S. MORIKAWA et al., (Virus Research, 1991 , 21 , 53-63)].
[0009] The nucleotide sequences of three proviral clones derived from American FIV isolates (Petaluma strain) have been described (clones FIV34TF10, FIV14 and isolate PPR) [R. A. OLMSTED et al., (Proc. Natl. Acad. Sci. USA, 1989, 86, 2448-2452); T. R. PHILIPPS et al., 1990; R .L. TALBOTT et al., (Proc. Natl. Acad. Sci. USA, 1989, 86, 5743-5747)] and compared with two Swiss isolates (S. MORIKAWA et al.). This comparison led S. MORIKAWA et al. to specify the presence of certain conserved regions and certain variable regions within the env gene of FIV.
[0010] French strains have also been isolated (strains Wo and Me) [MORAILLON A. et al., 1992, Vet. Mic, 31 , 41-45, In vitro properties and experimental pathogenic effect of three feline immunodeficiency viruses isolated from cats with terminal diseases].
[0011] It has now been known for that feline infection with the FIV virus is an old inflection that has touched domesticated cats and other felines for years. This problem raises significant health problems for domestic cats (See for example G. Pancino et al., Annales de L'lnstitut Pasteur 5(1), 25- 34 (1994) and endinelli et al. Clinical Microbiology Reviews, 8(1 ), 87-112 (1995).
[0012] It is known that in the treatment of AIDS in humans existing therapies use the so called "triple therapy" regiment which is costly and now is more and more questionable due to the emergence of HIV virus
strains that are resistant to the drugs that make up the "triple therapy" regimen.
[0013] Based on the high cost of therapy regimens such as the "triple therapy" regimen, it is not conceivable that such treatments would be made available for the treatment of domestic cats infected with the FIV virus.
[0014] By contrast, peptide based therapies present a cost effective alternative to the drugs used in the triple therapy regimen. Therefore, there remains a need in veterinary medicine for peptide based effective therapeutic agents.
SUMMARY OF THE INVENTION
[0015] The present invention provides novel peptides comprising at least 25 and at most 40 consecutive amino acids selected from the regions 649- 696 and 729-782 of the gp36 protein of a FIV strain, or to a corresponding consensus sequence. The peptides of the invention also include analogs wherein K is replaced with R and/or R is replaced with K at on or more positions.
[0016] In a preferred embodiment, the invention provides comprising at least 30 consecutive amino acids from the sequences 649-696 and 729- 782.
[0017] Preferred peptides have sequences selected from SEQ ID NO 1- 50.
[0018] The invention also provides therapeutic agents comprising one or more peptides according to the invention in combination with an excipient and/or a pharmaceutical carrier.
[0019] The invention also provides a method of treating a feline infected with FIV virus, wherein the method comprises administering to the feline a
therapeutically effective amount of a therapeutic agent comprising one or more peptides according to the invention.
[0020] The invention further provides a method of screening for FIV infection comprising: a) attaching a peptide according to the invention to a solid support, b) contacting a biological sample with the peptide to allow binding of anti-FIV antibodies to the peptide for a time sufficient to form a peptide- antibody complex, c) reacting said complex with anti-feline antibodies, and d) detecting the anti-feline antibodies if present.
Preferred antibodies have a label selected from the group consisting of a radioisotope, an enzyme, and a fluorophore. DETAILED DESCRIPTION OF SELECTED EMBODIMENTS OF THE INVENTION
[0021] The present invention provides new peptides suitable as veterinary therapeutic agents for the treatment of FIV infection in cats. The peptides of the invention are advantageous in that they can prevent or interfere with the fusion of the virus into a target cell (mainly T lymphocytes) through the membrane of the cell.
[0022] The peptides of the invention have sequences which correspond to highly conserved regions of the trans-membrane (TM) envelope protein of the FIV virus. Thus, it is highly unlikely that viral strains that are resistant to the peptides of the invention will appear. Moreover, these peptides are important, and even indispensable to viral activity and include key amino acids which cannot mutate without compromising the entry of the virus into the target cell and the replication of the virus.
[0023] It is possible to demonstrate the inhibition effect of the peptides on viral entry into the target cells through various known tests, in particular the test of inhibition of the formation of syncitia. For example, the method
described by S. Lombardi et al., Virology, 220, 274-284 (1996) can be used. This method employs kidney fibroblastoid cell lines of Crandell feline referred to as CrFK. The cells are cultured by known techniques. The investigative peptide is then added at a concentration varying between 0.01 to 25 μg/ml to fractions of 0.8 ml containing 2104 CrFK cells. FIV virus is isolated from a cat that is sera negative to FELV (detected with snap test IDEXX) and multiplied continuously. FELV designates feline leukemia virus. After six days of culturing the number of syncitia formed is counted with the microscope. For the comparative tests, instead of the peptides being tested either a peptide with the same amino acids as the tested peptide arranged in a random sequence, or a neuropeptide marketed by NEOSYSTEM of Strasbourg France under the name SC371.
[0024] The peptides of the invention inhibit the formation of syncitia. The degree of inhibition is dose dependent.
[0025] The peptides that form the active agent of the therapeutic agents according to the invention correspond to sequences contained in the sequence of the protein gp36 of the FIV virus. These peptides have a sequence containing at least 25 consecutive peptidic motifs (residues of amino acids), more particularly at least 30 consecutive peptidic motifs contained in the sequence 649-696 and 729-782 of the gp 36 protein of the FIV virus or a corresponding consensus sequence. The peptides contain at most 40 peptidic motifs.
[0026] Table 1 shows the sequences 649-782 of the gp36 protein for various known strains of the FIV virus. These sequences are available, for example from the database SWISSPROT. The SWISSPROT codes for the strains are indicated in Table 1. It is therefore easy to identify the sequences mentioned in the present application through the information provided in Table 1. Table 2 shows the 649-782 consensus sequence.
[0027] In the sequences of Tables 1 and 2 K may be replaced with R and R with K. Similarly, I may be replaced with L and L with I.
[0028] The peptides defined above can be used as therapeutic agents in the treatment of cats infected with the FIV virus. The peptides can be administered in a dosage ranging from 0.1 to 2 mg/kg of body weight.
[0029] A therapeutic agent according to the invention will contain at least one peptide as defined herein, and possibly an excipient and/or a suitable pharmaceutical carrier. The therapeutic agent can be administered, for example, parenterally or through an IV injection. The therapeutic agent may be in the form of a solution or injectible suspension or in the form of lyophilized powder containing the peptide as active agent, with optionally a conventional lyophilization adjuvant. The lyophilized powder allows the reconstitution of the injectable suspension.
[0030] The invention also provides therapeutic agent methods against FIV infection in cats. The therapies are based on the administration of one or more peptides according to the invention.
[0031] The following Example illustrates the invention.
Example
[0032] The peptide corresponding to the sequence 742-777 shown in Table 2 was prepared. Then a powder containing the peptide was prepared and lyophilized from a sterile and apyrogenic aqueous solution. An injectable solution is prepared from the lyophilized powder with apyrogenic serum to form an injectable isotonic solution.
[0033] The peptide corresponding to the 742-777 sequence can be replaced by anyone of the peptides of Table 1 corresponding to the sequence 742-777 or anyone of the peptides corresponding to the sequence 654-691 presented in Tables 1 and 2 or a peptide corresponding to one of the sequences 734-762 shown in Tables 1 and 2. The invention
also contemplates a peptide resulting from the association of a peptide corresponding to the sequence 742-777 with a peptide selected from the sequences 734-762 and/or a peptide selected from the sequences 654- 692 from Tables 1 and 2.
Table 1
TABLEAU 1
GP36 FIVPE KTGIQQ QKWEDWVRWΪGNI PQ
GP36~ Fivσi GLQQLiaKKrEDWVGWIGNIPQ
GP3 S" "ro/wo KKGIiQQliQE EDWVGWΪGNI PQ
GP36" FIVU2 RKGLQQI.QEWEDWVGWl.GNΪER
GP36" "j?ιws KGLQQLQEWEDWGWIGNIPQ '
GP3 S IVSD KQG QKIigjiWQDTOIG IGKr'PQ,'
GP36 ETVT2 KTGIQQLQKWEITOVG IGKr EQ
Table 2
TABLEAU 2
H Q E A I E K V T E A L K I N N L Numέrotation 6496506516526536546556566576586596606616626631664665
R L V T L E H Q V L V I G L K V E Numέrotation 666667668669670671672673674675676677678679680681682
A M E K F L Y T A F A M Q E L .G C Numέrotation 683684685686687688689690691692693694695696697698699
N Q N Q F F C K V P P E L W T R Y Numέrotation 700701702703704705706707708709710711712713714715716
N M T I N Q T I W N H G N I T L G Numέrotation 717718719720721722723724725726727728729730731732733
E W Y N Q T K D L Q Q K F Y E I I Numέrotation 734735736737738739740741742743744745746747748749750
M D I E Q N N V Q G K K G I Q Q L
Numέrotation 751752753754755756757758759760761762763764765766.767
Q K W E D W V G W I G N I P Q Numέrotation 768769770771772773774775776777778779780781782
SEQUENCE LISTING
<210> 1
<211> 48
<212> PRT
<213> F1NPE
<400> SEQ ID NO 1
His Gin Glu Ala He Glu Lys Nal Thr Gly Ala
Leu Lys lie Asn Asn
1 5 10
15
Leu Arg Leu Nal Thr Leu Glu His Gin Nal Leu Nal He Gly Leu Lys 20 25
30
Nal Glu Ala Met Glu Lys Phe Leu Tyr Thr Ala Phe Ala Met Gin Glu
35 40 45
<210> 2
<211> 48
<212> PRT
<213> FIVUl
<400> SEQ ID NO 2
Gin Gin Glu Ala He Glu Lys Nal Thr Glu Ala Leu Lys He Thr Asn
1 5 10
15
Leu Arg Leu Nal Thr Leu Glu His Gin Nal Leu Nal lie Gly Leu Lys 20 25
30
Nal Glu Ala Met Glu Lys Phe Leu Tyr Thr Ala Phe Al Met Gin Glu
35 , 40 45
<210> 3
<211> 48
<212> PRT
<213> FINWO
<400> SEQ ID NO 3
His Gin Glu Ala He Glu Lys Nal Thr Glu Ala Leu Lys He Asn Asn
1 5 10
15
Leu Arg Leu Nal Thr Leu Glu His Gin Nal Leu Nal He Gly Leu Lys 20 25 30
Nal Glu Ala Met Glu Lys Phe Leu Tyr Thr Ala Phe Ala Met Gin Glu
35 40 45
<210> 4 <211> 48 <212> PRT <213> F1NU2 <400> SEQ ID NO 4 His Gin Glu Thr He Glu Lys He Thr Glu Ala Leu Lys Nal Asn Asn 1 5 10
15
Leu Arg Leu Nal Thr Leu Glu His Gin Nal Leu Nal He Gly Leu Lys 20 25
30
Nal Glu Ala He Glu Lys Phe Leu Tyr Thr Ala Phe Ala Met Gin Glu
35 40 45
<210> 5 <211> 48 <212> PRT <213> FINU8 <400> SEQ ID NO 5 His Gin Glu Thr He Glu Lys Val Thr Glu Ala Leu Lys He Asn Asn 1 5 10
15
Leu Arg Leu Nal Thr Leu Glu His Gin Nal Leu Nal He Gly Leu Lys
20 25 30
Val Glu Ala Met Glu Lys Phe Leu Tyr Thr Ala Phe Ala Met Gin Glu
35 40
45
<210> 6
<211> 48
<212> PRT
<213> FINSD
<400> SEQ ID NO 6
His Gin Glu Ala Leu Asp Lys He Thr Glu Ala Leu Lys He Asn Asn
1 5 10
15
Leu Arg Leu Val Thr Leu Glu His Gin Met Leu Nal He Gly Leu Lys 2C ) 25 30
Nal Glu Ala He Glu Lys Phe Leu Tyr Thr Ala Phe Ala Met Gin Glu
35 40 45
<210> 7
<211> 48
<212> PRT
<213> FΓVT2
<400> SEQ HO NO 7
His Gin Gin Ala Leu Glu Lys He Thr Glu Ala Leu Lys He Asn Asn
1 5 10
15
Leu Arg Leu He Thr Leu Glu His Gin Val Leu Val He Gly Leu Arg 20 25
30
Nal Glu Ala He Glu Lys Phe Leu Tyr Thr Ala Phe Ala Met Gin Glu 35 40 45
<210> 8
<211> 73
<212> PRT
<213> FΓVPE
<400> SEQ ID NO 8
Leu Glu Leu Trp Thr Arg Tyr Asn Met Thr He
Asn Gin Thr He Trp
1 5 10
15
Asn His Gly Asn He Thr Leu Gly Glu Trp Tyr Asn Gin Thr Lys Asp 20 25
30
Leu Gin Gin Lys Phe Tyr Glu He He Met Asp He Glu Gin Asn Asn
35 40
45
Nal Gin Gly Lys Thr Gly He Gin Gin Leu Gin
Lys Trp Glu Asp Trp
50 55
60
Nal Arg Trp He Gly Asn He Pro Gin
65 70
<210> 9
<211> 73
<212> PRT
<213> FINTJ] L
<400> SEQ ID NO 9
Pro Glu Leu Trp Arg Arg Tyr Asn Met Thr He
Asn Gin Thr He Trp
1 5 10
15
Asn His Gly Asn He Thr Leu Gly Glu Trp Tyr
Asn Gin Thr Lys Asp 20 25
30
Leu Gin Lys Lys Phe Tyr Gly He He Met Asp He Glu Gin Asn Asn 35 40
45
Nal Gin Gly Lys Lys Gly Leu Gin Gin Leu Gin
Lys Trp Glu Asp Trp
50 55
60
Nal Gly Trp He Gly Asn He Pro Gin
65 70
<210> 10
<211> 73
<212> PRT
<213> FΓVWO
<400> SEQ ID NO IC )
Ser Ala Leu Trp Glu Arg Tyr Asn Met Thr He Asn Gin Thr He Trp
1 5 10
15
Asn His Gly Asn He Thr Leu Gly Glu Trp Tyr
Asn Gin Thr Lys Asp 20 25
30
Leu Gin Gin Arg Phe Tyr Glu He He Met Asp He Glu Gin Asn Asn
35 40
45
Val Gin Gly Lys Lys Gly Leu Gin Gin Leu Gin Glu Tip Glu Asp Tip 50 55 60
Val Gly Trp He Gly Asn He Pro Gin
65 70
<210> 11
<211> 73
<212> PRT
<213< FINU2 ^
<400> SEQ ID NO 11
Pro Glu Leu Trp Gin Arg Tyr Asn Met Thr He
Asn Gin Thr He Trp
1 5 10
15
Asn His Gly Asn He Thr Leu Gly Glu Trp Tyr Asn Gin Thr Lys Asp 20 25
30
Leu Gin Gin Lys Phe Tyr Glu He He Met Asp
Met Glu Gin Asn Asn
35 40
45
Nal Gin Gly Arg Lys Gly Leu Gin Gin Leu Gin Glu Trp Glu Asp Trp 50 55 60
Nal Gly Trp Leu Gly Asn He Pro Arg
65 70
<210> 12
<211> 73
<212> PRT
<213> FINU8
<400> SEQ ID NO 12 •
Pro Glu Leu Trp Lys Arg Tyr Asn Met Thr He Asn Gin Thr He Trp
1 5 10 15
Asn His Gly Asn He Thr Leu Gly Glu Trp Tyr Asn Gin Thr Lys Glu 20 25
30
Leu Gin Gin Lys Phe Tyr Glu He He Met Asn He Glu Gin Asn Asn
35 40
45
Nal Gin Nal Lys Lys Gly Leu Gin Gin Leu Gin Glu Trp Glu Asp Trp 50 55 60
Nal Gly Trp He Gly Asn He Pro Gin
65 70
<210> 13
<211> 73
<212> PRT
<213> FINSE >
<400> SEQ ID NO 13
Lys Glu Leu Trp Leu Arg Tyr Asn Met Thr Leu
Asn Gin Thr He Trp
1 5 10
15
Asn His Gly Asn lie Thr Leu Gly Glu Trp Tyr Asn Gin Thr Lys Tyr 20 25
30
Leu Gin Gin Lys Phe Tyr Glu He He Met Asp He Glu Gin Asn Asn
35 40
45
Nal Gin Gly Lys Gin Gly Leu Gin Lys Leu Gin Asn Trp Gin » Asp Trp 50 55 60
Met Gly Tip He Gly Lys He Pro Gin
65 70
<210> 14
<211> 73
<212> PRT
<213> FINT2
<400> SEQ ID NO 14
Pro Ser Leu Trp Ser Met Tyr Asn Met Thr Leu Asn Gin Thr lie Tip
1 5 10
15
Asn His Gly Asn He Ser Leu Gly Asn Tip Tyr Asn Gin Thr Arg Asp
20 25
30
Leu Gin Asn Lys Phe Tyr Glu He He Met Asp He Glu Gin Asn Asn 35 40
45
Nal Gin Gly Lys Thr Gly He Gin Gin Leu Gin Lys Trp Glu Asn Trp 50 55 60
Nal Gly Trp He Gly Lys He Pro Gin
65 70
<210> 15
<211> 73
<212> PRT
<213>
<220>
<223> consensus sequence < ι>f a fragment of FlVprotein gp36
<400> SEQ ID NO 15
Pro Glu Leu Trp Thr Arg Tyr Asn Met Thr He
Asn Gin Thr He Trp
1 5 10
15
Asn His Gly Asn He Thr Leu Gly Glu Trp Tyr
Asn Gin Thr Lys Asp 20 25
30
Leu Gin Gin Lys Phe Tyr Glu He He Met Asp
He Glu Gin Asn Asn
35 40
45
Val Gin Gly Lys Lys Gly He Gin Gin Leu Gin Lys Trp Glu Asp Trp 50 55 60
Val Gly Trp He Gly Asn He Pro Gin
65 70
<210> 16
<211> 38
<212> PRT
<213> FΓVPE
<400> SEQ ID NO K
Glu Lys Val Thr Gly Ala Leu Lys He Asn Asn Leu Arg Leu Val Thr
1 5 10
15
Leu Glu His Gin Val Leu Val He Gly Leu Lys
Val Glu Ala Met Glu
20 25
30
Lys Phe Leu Tyr Thr Ala
35
<210> 17 <211> 38 <212> PRT <213> F1NU1 <400> SEQ ID NO 17 Glu Lys Val Thr Glu Ala Leu Lys He Thr Asn Leu Arg Leu Val Thr 1 5 10 15
Leu Glu His Gin V Vaall Leu Val He Gly Leu Lys Val Glu Ala MMeett Glu
30
Lys Phe Leu Tyr T Thhrr Ala
35
<210> 18 <211> 38 <212> PRT <213> F1NWO or F1NU8 <400> SEQ ID NO 18 Glu Lys Val Thr Glu Ala Leu Lys He Asn Asn Leu Arg Leu Val Thr 1 5 10
15
Leu Glu His Gin Val Leu Val He Gly Leu Lys Val Glu Ala Met Glu 20 25
30
Lys Phe Leu Tyr Thr Ala
35
<210> 19 <211> 38 <212> PRT <213> F1NU2 <400> SEQ ID NO 19 Glu Lys He Thr Glu Ala Leu Lys Val Asn Asn
Leu Arg Leu Nal Thr 5 10
15
Leu Glu His Gin Val Leu Val He Gly Leu Lys Val Glu Ala He Glu
20 25 30
Lys Phe Leu Tyr Thr Ala
35
<210> 20
<211> 38
<212> PRT
<213> FΓVSD
<400> SEQ ID NO 2C )
Asp Lys He Thr Glu Ala Leu Lys He Asn Asn Leu Arg Leu Val Thr 1 5 10
15
Leu Glu His Gin Met Leu Val He Gly Leu Lys
Val Glu Ala He Glu 20 1 25
30
Lys Phe Leu Tyr Thr Ala 35
<210> 21
<211> 38
<212> PRT
<213> FIVT2
<400> SEQ ID NO 21 L
Glu Lys He Thr Glu Ala Leu Lys He Asn Asn Leu Arg Leu He Thr
1 5 10
15
Leu Glu His Gin Nal Leu Val He Gly Leu Arg Val Glu Ala He Glu 20 25
30
Lys Phe Leu Tyr Thr Ala
35
<210> 22
<211> 40
<212> PRT
<213> FΓVPE
<400> SEQ ID NO 22
Tyr Asn Met Thr He Asn Gin Thr He Trp Asn His Gly Asn He Thr
1 5 10
15
Leu Gly Glu Trp Tyr Asn Gin Thr Lys Asp Leu Gin Gin Lys Phe Tyr 2( ) 25 30
Glu He He Met Asp He Glu Gin 35 40
<210> 23
<211> 40
<212> PRT
<213> F1NU1
<400> SEQ ED NO 23
Tyr Asn Met Thr He Asn Gin Thr He Tip Asn His Gly Asn He Thr
1 5 10
15
Leu Gly Glu Trp Tyr Asn Gin Thr Lys Asp Leu Gin Lys Lys Phe Tyr
20 25
30
Gly He He Met Asp He Glu Gin
35 40
<210> 24
<211> 40
<212> PRT
<213> FΓVWO
<400> SEQ ID NO 24
Tyr Asn Met Thr He Asn Gin Thr He Trp Asn His Gly Asn He Thr
1 5 10
15
Leu Gly Glu Trp Tyr Asn Gin Thr Lys Asp Leu Gin Gin Arg Phe Tyr 20 25
30
Glu He He Met Asp He Glu Gin 35 40
<210> 25
<211> 40
<212> PRT
<213> F1NU2
<400> SEQ ID NO 25
Tyr Asn Met Thr He Asn Gin Thr He Trp Asn His Gly Asn He Thr
1 5 10
15
Leu Gly Glu Trp Tyr Asn Gin Thr Lys Asp Leu Gin Gin Lys Phe Tyr
20 25
30
Glu He He Met Asp Met Glu Gin
35 40
<210> 26
<211> 40
<212> PRT
<213> FINU8
<400> SEQ ID NO 26
Tyr Asn Met Thr He Asn Gin Thr He Trp Asn His Gly Asn He Thr
1 5 10
15
Leu Gly Glu Trp Tyr Asn Gin Thr Lys Glu Leu Gin Gin Lys Phe Tyr
20 25
30
Glu He He Met Asn He Glu Gin 35 40
<210> 27
<211> 40
<212> PRT
<213> FΓVSD
<400> SEQ ID NO 27
Tyr Asn Met Thr Leu Asn Gin Thr He Trp Asn
His Gly Asn He Thr
1 5 10
15
Leu Gly Glu Trp Tyr Asn Gin Thr Lys Tyr Leu Gin Gin Lys Phe Tyr 20 25
30
Glu He He Met Asp He Glu Gln
35 40
<210> 28
<211> 40
<212> PRT
<213> F1VT2
<400> SEQ ID NO 2Σ >
Tyr Asn Met Thr Leu Asn Gin T r He Trp Asn His Gly Asn He Ser
1 5 10
15
Leu Gly Asn Trp Tyr Asn Gin Thr Arg Asp Leu Gin Asn Lys Phe Tyr
20 25
30
Glu He He Met Asp He Glu Gin 35 40
<210> 29
<211> 36
<212> PRT
<213> F1NPE
<400> SEQ ID NO 29
Leu Gin Gin Lys Phe Tyr Glu He He Met Asp
He Glu Gin Asn Asn
1 5 10
15
Nal Gin Gly Lys Thr Gly He Gin Gin Leu Gin
Lys Trp Glu Asp Trp
20 25
30
Nal Arg Trp He
35
<210> 30
<211> 36
<212> PRT
<213> FlNUl 1
<400> SEQ ID NO 30
Leu Gin Lys Lys Phe Tyr Gly He He Met Asp
He Glu Gin Asn Asn
1 5 10
15
Nal Gin Gly Lys Lys Gly Leu Gin Gin Leu Gin
Lys Tip Glu Asp Trp 20 25 30
Nal Gly Trp He
35
<210> 31
<211> 36
<212> PRT
<213> F1NWO
<400> SEQ IT) NO 31
Leu Gin Gin Arg Phe Tyr Glu He He Met Asp
He Glu Gin Asn Asn
1 5 10
15
Nal Gin Gly Lys Lys Gly Leu Gin Gin Leu Gin
Glu Trp Glu Asp Trp 2C ) 25
30 Val Gly Trp He
35
<210> 32 <211> 36 <212> PRT <213> F1NU2 <400> SEQ ED NO 32 Leu Gin Gin Lys Phe Tyr Glu He He Met Asp
Met Glu Gin Asn Asn 1 5 10 15 Nal Gin Gly Arg Lys Gly Leu Gin Gin Leu Gin
Glu Trp Glu Asp Trp
20 25
30
Val Gly Trp Leu
35
<210> 33 <211> 36 <212> PRT <213> F1NU8 <400> SEQ ID NO 33 Leu Gin Gin Lys Phe Tyr Glu He He Met Asn He Glu Gin Asn Asn 1 5 10
15
Nal Gin Val Lys Lys Gly Leu Gin Gin Leu Gin Glu Trp Glu Asp Trp 20 25
30
Nal Gly Trp He
35
<210> 34 <211> 36 <212> PRT <213> FINSD <400> SEQ ID NO 34 Leu Gin Gin Lys Phe Tyr Glu He He Met Asp He Glu Gin Asn Asn 1 5 10
15
Nal Gin Gly Lys Gin Gly Leu Gin Lys Leu Gin Asn Trp Gin Asp Trp
20 25
30
Met Gly Tip He
35
<210> 35
<211> 36
<212> PRT
<213> FΓVT2
<400> SEQ ID NO 3
Leu Gin Asn Lys Phe Tyr Glu He He Met Asp He Glu Gin Asn Asn
1 5 10
15
Val Gin Gly Lys Thr Gly He Gin Gin Leu Gin
Lys Trp Glu Asn Trp 20 25
30
Val Gly Trp He
35
<210> 36
<211> 36
<212> PRT
<213>
<220>
<223> Consensus sequence ι of fragment eFPV gp36
<400> SEQ ID NO 3t
Leu Gin Gin Lys Phe Tyr Glu He He Met Asp He Glu Gin Asn Asn
1 5 10
15
Val Gin Gly Lys Lys Gly He Gin Gin Leu Gin Lys Trp Glu Asp Trp 2C ) 25 30
Val Gly Trp He
35
<210> 37
<211> 29
<212> PRT
<213> FΓVPE
<400> SEQ ID NO Tι 1
Glu Tip Tyr Asn Gin Thr Lys Asp Leu Gin Gin
Lys Phe Tyr Glu He
1 5 10
15
He Met Asp He Glu Gin Asn Asn Val Gin Gly
Lys Thr 20 25
<210> 38
<211> 29
<212> PRT
<213> FiNUl
<400> SEQ ID NO 3c~ i
Glu Trp Tyr Asn Gin Thr Lys Asp Leu Gin Lys
Lys Phe Tyr Gly He
1 5 10
15
He Met Asp He Glu Gin Asn Asn Val Gin Gly Lys Lys 20 25
<210> 39
<211> 29
<212> PRT
<213> FΓVWO
<400> SEQ ID NO 39
Glu Trp Tyr Asn Gin Thr Lys Asp Leu Gin Gin Arg Phe Tyr Glu He
1 5 10
15
He Met Asp He Glu Gin Asn Asn Val Gin Gly
Lys Lys 20 25
<210> 40
<211> 29
<212> PRT
<213> F1NU2
<400> SEQ ID NO 40
Glu Trp Tyr Asn Gin Thr Lys Asp Leu Gin Gin Lys Phe Tyr Glu He
1 5 \ 10
15
He Met Asp Met Glu Gin Asn Asn Val Gin Gly Arg Lys 20 25
<210> 41
<211> 29
<212> PRT
<213> FINU8
<400> SEQ ID NO 41
Glu Trp Tyr Asn Gin Thr Lys Glu Leu Gin Gin Lys Phe Tyr Glu He
1 5 10
15
He Met Asn He Glu Gin Asn Asn Val Gin Val
Lys Lys 20 25
<210> 42
<211> 29
<212> PRT
<213> F1NSD 1
<400> SEQ ED NO 42
Glu Tip Tyr Asn Gin Thr Lys Tyr Leu Gin Gin
Lys Phe Tyr Glu He
1 5 10
15
He Met Asp He Glu Gin Asn Asn Val Gin Gly Lys Gin 20 25
<210> 43
<211> 29
<212> PRT
<213> F1NT2
<400> SEQ ID NO 43
Asn Trp Tyr Asn Gin Thr Arg Asp Leu Gin Asn
Lys Phe Tyr Glu He
1 5 10
15
He Met Asp He Glu Gin Asn Asn Val Gin Gly
Lys Thr 20 25
<210> 44
<211> 29
<212> PRT
<213>
<223> Consensus sequence fragment FIN gp36
<400> SEQ ID NO 44 ^
Glu Trp Tyr Asn Gin Thr Lys Asp Leu Gin Gin
Lys Phe Tyr Glu He
1 5 10
15
He Met Asp He Glu Gin Asn Asn Val Gin Gly Lys Lys
<210> 45
<211> 25
<212> PRT
<213> FINPE or FlNrø
<400> SEQ ID NO 45
Thr Ile Tip Asn His Gly Asn He Thr Leu Gly Glu Trp Tyr Asn Gin
1 5 10
15
Thr Lys Asp Leu Gin Gin Lys Phe Tyr 20 25
<210> 46
<211> 25
<212> PRT
<213> FΓVUI
<400> SEQ ID NO 4i
Thr He Tip Asn His Gly Asn He Thr Leu Gly Glu Trp Tyr Asn Gin
1 5 10 15
Tlir Ly Asp Leu Gin Lys Lys Phe Tyr 20 25
<210> 47
<211> 25
<212> PRT
<213> F1NWO
<400> SEQ ID NO 47
Ηir He Trp Asn His Gly Asn He Thr Leu Gly Glu Tip Tyr Asn Gin
1 5 10
15
Thr Lys Asp Leu Gin Gin Arg Phe Tyr
20 25
<210> 48
<211> 25
<212> PRT
<213> F1NU8
<400> SEQ ID NO 48
Thr He Tip Asn His Gly Asn lie Thr Leu Gly Glu Tip Tyr Asn Gin
1 5 10
15
Thr Lys Glu Leu Gin Gin Lys Phe Tyr 20 25
<210> 49
<211> 25
<212> PRT
<213> FINSD
Thr He Tip Asn His Gly Asn He Thr Leu Gly Glu Trp Tyr Asn Gin
1 5 10
15
Thr Lys Tyr Leu Gin Gin Lys Phe Tyr 20 25
<210> 50
<211> 25
<212> PRT
<213> FIVT2
<400> SEQ ID NO 5C 1
Thr He Trp Asn His Gly Asn He Ser Leu Gly Asn Trp Tyr Asn Gin
1 5 10
15
Thr Arg Asp Leu Gin Asn Lys Phe Tyr
Claims
1. A peptide comprising at least 25 and at most 40 consecutive amino acids selected from the regions 649-696 and 729-782 of the gp36 protein of a FIV strain, or to a corresponding consensus sequence and analogs thereof.
2. A peptide according to Claim 1 , wherein K is replaced with R and/or R is replaced with K at on or more positions.
3. A peptide according to Claim 1 , wherein the peptide comprises at least 30 consecutive amino acids from the sequences 649- 696 and 729-782.
4. A peptide according to Claim 1 or 2 wherein the sequence of the peptide is selected from SEQ ID NO 1-50.
5. A peptide according to Claim 1 , wherein the peptide comprises at least 25 consecutive amino acids selected from the sequences 654-691 , 742-777 and 734-762.
6. A therapeutic agent comprising one or more peptides according to Claim 1 in combination with an excipient and/or a pharmaceutical carrier.
7. A method of treating a feline infected with FIV virus, wherein the method comprises administering to the feline a therapeutically effective amount of a therapeutic agent comprising one or more peptides of Claim 1.
8. A peptide derived from feline immunodeficiency virus strain peptide having a sequence selected from SEQ ID NO 1 to SEQ ID NO 50.
9. A method of screening for FIV infection comprising a) attaching the peptide of claim 8 to a solid support, b) contacting a biological sample with the peptide to allow binding of anti-FIV antibodies to the peptide for a time sufficient to form a peptide- antibody complex, c) reacting said complex with anti-feline antibodies, d) detecting the anti-feline antibodies if present.
10. The method of claim 9 wherein the anti-feline antibodies have a label selected from the group consisting of a radioisotope, an enzyme, and a fluorophore.
11. A kit for the diagnosis of FIV infection comprising the peptide of claim 8 and suitable buffers, labels, and control sera.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0110910A FR2828686B1 (en) | 2001-08-17 | 2001-08-17 | NOVEL PEPTIDES AND THEIR USE AS MEDICAMENTS AGAINST IVF INFECTION IN CATS |
| FR0110910000 | 2001-08-17 | ||
| FR0115424000 | 2001-11-11 | ||
| FR0115424A FR2828687B1 (en) | 2001-08-17 | 2001-11-29 | NOVEL PEPTIDES AND THEIR USE AS MEDICAMENTS AGAINST IVF INFECTION IN CATS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2003015814A1 true WO2003015814A1 (en) | 2003-02-27 |
Family
ID=26213149
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2002/026247 WO2003015814A1 (en) | 2001-08-17 | 2002-08-19 | New peptides and use thereof in therapeutic agents against feline fiv infection |
Country Status (2)
| Country | Link |
|---|---|
| FR (1) | FR2828687B1 (en) |
| WO (1) | WO2003015814A1 (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7201903B2 (en) | 2003-09-11 | 2007-04-10 | Idexx Laboratories, Inc. | Method and device for detecting feline immunodeficiency virus |
| US7285278B2 (en) | 2004-06-30 | 2007-10-23 | Idexx Laboratories, Inc. | Method and device for detecting feline immunodeficiency virus |
| US7285272B2 (en) | 2003-12-18 | 2007-10-23 | Idexx Laboratories, Inc. | Method and device for detecting feline immunodeficiency virus |
| US7291338B2 (en) | 2005-03-09 | 2007-11-06 | Idexx Laboratories, Inc. | Method and device for detecting feline immunodeficiency virus |
| US7335360B2 (en) | 2004-06-30 | 2008-02-26 | Idexx Laboratories, Inc. | Method and device for detecting feline immunodeficiency virus |
| US7348136B2 (en) | 2004-02-19 | 2008-03-25 | Idexx Laboratories, Inc. | Method and device for detecting feline immunodeficiency virus |
| US8809004B2 (en) | 2010-04-02 | 2014-08-19 | Idexx Laboratories, Inc. | Detection of feline immunodeficiency virus |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5275813A (en) * | 1987-08-26 | 1994-01-04 | The Regents Of The University Of California | Methods and compositions for vaccinating against feline immunodeficiency virus |
| US5591572A (en) * | 1991-06-14 | 1997-01-07 | St. Vincents Institute Of Medical Research Limited | Detection of mammalian immunodeficiency viruses |
| US6107077A (en) * | 1987-08-26 | 2000-08-22 | Yamamoto; Janet K. | Feline lymphoid cell lines capable of producing FIV for FIV diagnostics and vaccines |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5223421A (en) * | 1989-10-25 | 1993-06-29 | The General Hospital Corporation | Identification of methionine Nα-acetyltransferase |
| US5736378A (en) * | 1991-09-12 | 1998-04-07 | The Scripps Research Institute | Molecular cloning and characterization of the feline immunodeficiency virus isolate PPR |
| ATE278018T1 (en) * | 1992-06-16 | 2004-10-15 | Centre Nat Rech Scient | NUCLEOTIDE AND PEPTIDE SEQUENCES OF CAT IMMUNO DEFICIENCY VIRUS, ISOLATE WO AND APPLICATIONS OF THE SEQUENCES IN DIAGNOSTICS AND FOR PREVENTING INFECTION |
| GB9219936D0 (en) * | 1992-09-21 | 1992-11-04 | Pitman Moore Inc | Vaccines |
-
2001
- 2001-11-29 FR FR0115424A patent/FR2828687B1/en not_active Expired - Fee Related
-
2002
- 2002-08-19 WO PCT/US2002/026247 patent/WO2003015814A1/en not_active Application Discontinuation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5275813A (en) * | 1987-08-26 | 1994-01-04 | The Regents Of The University Of California | Methods and compositions for vaccinating against feline immunodeficiency virus |
| US6107077A (en) * | 1987-08-26 | 2000-08-22 | Yamamoto; Janet K. | Feline lymphoid cell lines capable of producing FIV for FIV diagnostics and vaccines |
| US5591572A (en) * | 1991-06-14 | 1997-01-07 | St. Vincents Institute Of Medical Research Limited | Detection of mammalian immunodeficiency viruses |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7201903B2 (en) | 2003-09-11 | 2007-04-10 | Idexx Laboratories, Inc. | Method and device for detecting feline immunodeficiency virus |
| US7776546B2 (en) | 2003-09-11 | 2010-08-17 | Idexx Laboratories, Inc. | Method and device for detecting feline immunodeficiency virus |
| US7285272B2 (en) | 2003-12-18 | 2007-10-23 | Idexx Laboratories, Inc. | Method and device for detecting feline immunodeficiency virus |
| US7348136B2 (en) | 2004-02-19 | 2008-03-25 | Idexx Laboratories, Inc. | Method and device for detecting feline immunodeficiency virus |
| US7285278B2 (en) | 2004-06-30 | 2007-10-23 | Idexx Laboratories, Inc. | Method and device for detecting feline immunodeficiency virus |
| US7335360B2 (en) | 2004-06-30 | 2008-02-26 | Idexx Laboratories, Inc. | Method and device for detecting feline immunodeficiency virus |
| US7291338B2 (en) | 2005-03-09 | 2007-11-06 | Idexx Laboratories, Inc. | Method and device for detecting feline immunodeficiency virus |
| US8809004B2 (en) | 2010-04-02 | 2014-08-19 | Idexx Laboratories, Inc. | Detection of feline immunodeficiency virus |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2828687B1 (en) | 2003-12-12 |
| FR2828687A1 (en) | 2003-02-21 |
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