Mutated netrin 4, fragments thereof and uses thereof as drugs
AssigneesCentre National De La Recherche Scientifique, IVS Institut des Vaisseaux et du Sang, Inserm (Institut National De La Sante Et De La Rec
InventorsJean Plouet, Isabelle Clarisse Solange Plouet, Claire Charlotte Plouet, Anne Florence Plouet, Laurence Leconte, Esma Lejmi
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Abstract
The present invention relates to a protein comprising or consisting of one of the following sequences: the sequence SEQ ID NO: 2 or SEQ ID NO: 4, or a fragment of said sequence represented by one of the sequences SEQ ID NO: 2q, q varying from 3 to 36, or the sequence SEQ ID NO: 185 to SEQ ID NO: 209. It also relates to a nucleotide sequence coding for said protein.
Claims19
1-18. (canceled)
A protein comprising or consisting of one of the following sequences:
- the sequence SEQ ID NO:
- 2 or SEQ ID NO:
- 4, or
- a fragment of said sequence represented by one of the sequences SEQ ID NO:
- 2q, q varying from 3 to 36, or
- one of the sequences chosen among the group consisting in SEQ ID NO:
- 185 to SEQ ID NO:
- 209.
A nucleotide sequence coding for a protein comprising or consisting of one of the following sequences:
- the sequence SEQ ID NO:
- 2 or SEQ ID NO:
- 4, or
- a fragment of said sequence represented by one of the sequences SEQ ID NO:
- 2q, q varying from 3 to 36, or
- one of the sequences chosen among the group consisting in SEQ ID NO:
- 185 to SEQ ID NO:
- 209.
A pharmaceutical composition comprising as active substance:
- a protein comprising or consisting of one of the following sequences:
- the sequence SEQ ID NO:
- 2 or SEQ ID NO:
- 4, or
- a fragment of said sequence represented by one of the sequences SEQ ID NO:
- 2q, q varying from 3 to 36, or
- one of the sequences chosen among the group consisting in SEQ ID NO:
- 185 to SEQ ID NO:
- 209
- or
- a nucleotide sequence coding for a protein comprising or consisting of one the following sequences:
- the sequence SEQ ID NO:
- 2 or SEQ ID NO:
- 4, or
- a fragment of said sequence represented by one of the sequences SEQ ID NO:
- 2q, q varying from 3 to 36, or
- one of the sequences chosen among the group consisting in SEQ ID NO:
- 185 to SEQ ID NO:
- 209,
- or
- an antibody, characterized in that it is specifically directed against a protein comprising or consisting of one of the following sequences,
- the sequence SEQ ID NO:
- 2 or SEQ ID NO:
- 4, or
- a fragment of said sequence represented by one of the sequences SEQ ID NO:
- 2q, q varying from 3 to 36, or
- one of the sequences chosen among the group consisting in SEQ ID NO:
- 185 to SEQ ID NO:
- 209
- or
- an anti-idiotypic antibody of said antibody,
- or
- a Fab fragment of said anti-idiotypic antibody.
A method for the prevention or treatment of pathologies involving the inhibition of endothelial cell proliferation and/or migration, in particular for the prevention or treatment of pathologies chosen from the group consisting of:
- cancers and leukemia, myopia-complicating choroidal neovascularization, cornea neovascularaization, in particular graft rejection, glaucoma, diabetic retinopathies or premature retinopathies, rheumatoid arthritis, psoriasis arthritis, angioma, angiosarcoma, Castleman's disease, and Kaposi's sarcoma, or for the treatment of obesity or retinal neovascularization,
- said method comprising the administration, to a patient in a need thereof, of:
- a protein comprising or consisting of one of the following sequences:
- the sequence SEQ ID NO:
- 2 or SEQ ID NO:
- 4, or
- a fragment of said sequence represented by one of the sequences SEQ ID NO:
- 2q, q varying from 3 to 36, or
- one of the sequences chosen among the group consisting in SEQ ID NO:
- 185 to SEQ ID NO:
- 209
- or
- a nucleotide sequence coding for a protein comprising or consisting of one the following sequences:
- the sequence SEQ ID NO:
- 2 or SEQ ID NO:
- 4, or
- a fragment of said sequence represented by one of the sequences SEQ ID NO:
- 2q, q varying from 3 to 36, or
- one of the sequences chosen among the group consisting in SEQ ID NO:
- 185 to SEQ ID NO:
- 209,
- or
- an antibody, characterized in that it is specifically directed against a protein comprising or consisting of one of the following sequences,
- the sequence SEQ ID NO:
- 2 or SEQ ID NO:
- 4, or
- a fragment of said sequence represented by one of the sequences SEQ ID NO:
- 2q, q varying from 3 to 36, or
- one of the sequences chosen among the group consisting in SEQ ID NO:
- 185 to SEQ ID NO:
- 209
- or
- an anti-idiotypic antibody of said antibody,
- or
- a Fab fragment of said anti-idiotypic antibody.
A method for the prevention or treatment of pathologies involving the stimulation of endothelial cell proliferation and/or migration, in particular for the prevention or treatment of pathologies chosen from the group consisting of:
- ischemic pathologies such as arteries of lower limbs, myocardium infarct, cerebral vascular accidents, scleroderma, and Raynaud's disease,
- said method comprising the administration, to a patient in a need thereof, of:
- an antibody, characterized in that it is specifically directed against a protein comprising or consisting of one of the following sequences,
- the sequence SEQ ID NO:
- 2 or SEQ ID NO:
- 4, or
- a fragment of said sequence represented by one of the sequences SEQ ID NO:
- 2q, q varying from 3 to 36, or
- one of the sequences chosen among the group consisting in SEQ ID NO:
- 185 to SEQ ID NO:
- 209
- or
- a Fab fragment of said antibody.
A method for the prevention or treatment of non-tumoral pathologies linked to or caused by a pericyte or smooth muscular cell rarefaction, and requiring and activation of pericyte or smooth muscular cell proliferation or migration, said non-tumoral pathologies being in particular chosen from the group consisting of:
- age-related macular degeneration,
- neovascular glaucoma,
- psoriasis,
- atherosclerosis,
- intestinal malformations,
- Crohn's disease,
- vascular or sub-cortical vascular dementia,
- Alzheimer's disease,
- bone degenerative pathologies, and fractures, and
- aneurysms, and vascular dissections
- said method comprising the administration, to a patient in a need thereof, of:
- a protein comprising or consisting of one of the following sequences:
- the sequence SEQ ID NO:
- 2 or SEQ ID NO:
- 4, or
- a fragment of said sequence represented by one of the sequences SEQ ID NO:
- 2q, q varying from 3 to 36, or
- one of the sequences chosen among the group consisting in SEQ ID NO:
- 185 to SEQ ID NO:
- 209
- or
- a nucleotide sequence coding for a protein comprising or consisting of one of the following sequences:
- the sequence SEQ ID NO:
- 2 or SEQ ID NO:
- 4, or
- a fragment of said sequence represented by one of the sequences SEQ ID NO:
- 2q, q varying from 3 to 36, or
- one of the sequences chosen among the group consisting in SEQ ID NO:
- 185 to SEQ ID NO:
- 209,
- or
- an antibody, characterized in that it is specifically directed against a protein comprising or consisting of one of the following sequences,
- the sequence SEQ ID NO:
- 2 or SEQ ID NO:
- 4, or
- a fragment of said sequence represented by one of the sequences SEQ ID NO:
- 2q, q varying from 3 to 36, or
- one of the sequences chosen among the group consisting in SEQ ID NO:
- 185 to SEQ ID NO:
- 209
- or
- an anti-idiotypic antibody of said antibody,
- or
- a Fab fragment of said anti-idiotypic antibody.
A method for the treatment of cancer comprising the administration to a patient in a need thereof, of:
- the protein represented by SEQ ID NO:
- 2 or SEQ ID NO:
- 4, represented by one of the sequences SEQ ID NO:
- 2q, q varying from 3 to 36,
- the protein represented by one of the sequences chosen from among SEQ ID NO:
- 185 to SEQ ID NO:
- 209,
- in association with a chemotherapy agent.
A pharmaceutical composition comprising a chemotherapy agent, in association with the protein represented by SEQ ID NO:
- 2 or SEQ ID NO:
- 4, or in association with a fragment of said sequence SEQ ID NO:
- 2 or SEQ ID NO:
- 4, represented by one of the sequences SEQ ID NO:
- 2q, q varying from 3 to 36, or the protein represented by one of the sequences chosen among SEQ ID NO:
- 185 or SEQ ID NO:
- 209,
- said chemotherapy agent being a particular chosen from the group consisting of:
- doxorubicin, methotrexate, vinblastine, vincristine, cladribine, fluorouracil, cytarabine, anthracyclines, cisplatin, cyclophophamide, fludarabine, gemcitabine, aromatase inhibitors, irinotecan, navelbine, oxaliplatin, taxol, and docetaxel.
A protein comprising or consisting of:
- SEQ ID NO:
- 74, SEQ ID NO:
- 76, SEQ ID NO:
- 78, SEQ ID NO:
- 80, SEQ ID NO:
- 82, SEQ ID NO:
- 84, SEQ ID NO:
- 86, SEQ ID NO:
- 88, SEQ ID NO:
- 90, SEQ ID NO:
- 92, SEQ ID NO:
- 94, SEQ ID NO:
- 96, SEQ ID NO:
- 98, SEQ ID NO:
- 100, SEQ ID NO:
- 102, SEQ ID NO:
- 104, SEQ ID NO:
- 106, SEQ ID NO:
- 108, SEQ ID NO:
- 110, SEQ ID NO:
- 112, SEQ ID NO:
- 114, SEQ ID NO:
- 116, SEQ ID NO:
- 118, SEQ ID NO:
- 120, SEQ ID NO:
- 122, SEQ ID NO:
- 124, SEQ ID NO:
- 126, SEQ ID NO:
- 128, SEQ ID NO:
- 130, SEQ ID NO:
- 132, SEQ ID NO:
- 134, SEQ ID NO:
- 136, SEQ ID NO:
- 138, SEQ ID NO:
- 140, SEQ ID NO:
- 142, SEQ ID NO:
- 144, SEQ ID NO:
- 146, SEQ ID NO:
- 148, SEQ ID NO:
- 150, SEQ ID NO:
- 152, SEQ ID NO:
- 154, SEQ ID NO:
- 156, SEQ ID NO:
- 158, SEQ ID NO:
- 160, SEQ ID NO:
- 162, SEQ ID NO:
- 164, SEQ ID NO:
- 166, SEQ ID NO:
- 168, SEQ ID NO:
- 170, SEQ ID NO:
- 172, SEQ ID NO:
- 174.
A pharmaceutical composition comprising pericytes or vascular smooth muscle cells, in association with the protein represented by SEQ ID NO:
- 2 or SEQ ID NO:
- 4, or in association with a fragment of said sequence SEQ ID NO:
- 2 or SEQ ID NO:
- 4, represented by one of the sequences SEQ ID NO:
- 2q, q varying from 3 to 36, or in association with one of the sequences SEQ ID NO:
- 185 to SEQ ID NO:
- 209.
Dependencies are inferred from the claim text.