Glaxosmithkline Biologicals Sa

Novartis Ag

Philogen S.p.a.

Eidgenossische Technische Hochschule Zurich

Lorenzo Tarli

Mario Contorni

Dario Neri

Fredrik Nilsson

Luciano Zardi

Barbara Carnemolla

Laura Borsi

Cornelia Halin

Francesca Viti

Manfred Birchler

Factor H binding protein (fHBP) has been proposed for use in immunising against serogroup B meningococcus ('MenB'). This antigen can be efficiently adsorbed to an aluminium hydroxyphosphate adjuvant by (i) ensuring that adsorption takes place at a pH which is equal to or below the adjuvant's point of zero charge (PZC), and/or (ii) selecting a fHBP and adjuvant with an isoelectric point/PZC within the range of 5.0 to 7, and/or (iii) selecting a fHBP with an isoelectric point above the adjuvant's PZC and using a buffer to bring the pH to within 1.2 pH units of the PZC. The adsorption is particularly useful for compositions which include multiple fHBP variants, and also in situations where an aluminium hydroxide adjuvant should be avoided. Buffered pharmaceutical compositions can include at least two different meningococcal fHBP antigens, both of which are at least 85% adsorbed to aluminium hydroxyphosphate adjuvant.

Adjuvanting meningococcal factor H binding protein

Factor H binding protein (fHBP) has been proposed for use in immunizing against serogroup B meningococcus ('MenB'). This antigen can be efficiently adsorbed to an aluminum hydroxyphosphate adjuvant by (i) ensuring that adsorption takes place at a pH which is equal to or below the adjuvant's point of zero charge (PZC), and/or (ii) selecting a fHBP and adjuvant with an isoelectric point/PZC within the range of 5.0 to 7, and/or (iii) selecting a fHBP with an isoelectric point above the adjuvant's PZC and using a buffer to bring the pH to within 1.2 pH units of the PZC. The adsorption is particularly useful for compositions which include multiple fHBP variants, and also in situations where an aluminum hydroxide adjuvant should be avoided. Buffered pharmaceutical compositions can include at least two different meningococcal fHBP antigens, both of which are at least 85% adsorbed to aluminum hydroxyphosphate adjuvant.

Treatment of lesions of pathological angiogenesis, especially tumors, rheumatoid arthritis, diabetic retinopathy, age-related muscular degeneration, and angiomas. A conjugate is used comprising a molecule that exerts a biocidal or cytotoxic effect on target cells in the lesions and an antibody directed against an extracellular matrix component which is present in such lesions. The antibody may be directed against fibronectin-2 (IL-2), doxorubicin, interleukin-12 (IL-12), Interferon-&#x3b3; (IFN-&#x3b3;), Tumor Necrosis Factor &#x3b1; (TNF&#x3b1;) or Tissue Factor protein (which may be truncated).

Compositions and methods for treatment of angiogenesis in pathological lesions

Treatment of lesions of pathological angiogenesis, especially tumors, rheumatoid arthritis, diabetic retinopathy, age-related muscular degeneration. and angiomas. A conjugate is used comprising a molecule that exerts a biocidal or cytotoxic effect on target cells in the lesions and an antibody directed against an extracellular matrix component which is present in such lesions. The antibody may be directed against fibronectin-2 (IL-2), doxorubicin, interleukin-12(IL-12), Interferon-&#x3b3; (IFN-&#x3b3;), Tumor Necrosis Factor &#x3b1;(TNF&#x3b1;) or Tissue Factor protein (which may be truncated).

Factor H binding protein (fHBP) has been proposed for use in immunising against serogroup B meningococcus ('MenB'). This antigen can be efficiently adsorbed to an aluminum hydroxyphosphate adjuvant by (i) ensuring that adsorption takes place at a pH which is equal to or below the adjuvant's point of zero charge (PZC), and/or (ii) selecting a fHBP and adjuvant with an isoelectric point/PZC within the range of 5.0 to 7, and/or (iii) selecting a fHBP with an isoelectric point above the adjuvant's PZC and using a buffer to bring the pH to within 1.2 pH units of the PZC. The adsorption is particularly useful for compositions which include multiple fHBP variants, and also in situations where an aluminum hydroxide adjuvant should be avoided. Buffered pharmaceutical compositions can include at least two different meningococcal fHBP antigens, both of which are at least 85% adsorbed to aluminum hydroxyphosphate adjuvant.

The present invention relates to antibodies with sub-nanomolar affinity specific for a characteristic epitope of the ED-B domain of fibronectin, a marker of angiogenesis. Furthermore, it relates to the use of radiolabelled high affinity anti ED-B antibodies for detecting new-forming blood vessels in vivo and a diagnostic kit comprising said antibody. Furthermore, it relates to conjugates comprising said antibodies and a suitable photoactive molecules (e.g. an appropriately chosen photosensitizer or radionuclide), and their use for the selective light-mediated occlusion of new blood vessels.

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Siena, Italy

Lorenzo Tarli