Yeda Research and Develpment & Co. Ltd

Memorial Sloan Kettering Cancer Center

Yoram Salomon

Avigdor Scherz

Alexander Brandis

Hugo Scheer

Leszek Fiedor

Doron Eren

Arie Marcovich

Daniel Wagner

Efrat Rubinstein

Karin Neimann

Ohad Mazor

Michal Neeman

Avraham Cohen

Gerhard Hartwich

Jonathan Coleman

Kwanghee Kim

Liat Goldshaid

Dina Preise

Rachel Hamri

Shimon Gross

Assaf Gilead

Nina Kammhuber

Lilach Agemy

An anti-myeloid-derived suppressor cells agent ('anti-MDSCs agent') and a bacteriochlorophyll derivative (hereinafter 'Bchl-D) for use in combination therapy for cancer, wherein the anti-MDSC agent and the Bchl-D are administered sequentially and the administration of the Bchl-D is followed by photodynamic therapy (PDT) or vascular targeted PDT (VTP).

Combinational therapies for treatment of cancer comprising a bacteriochlorophyll derivative

An ophthalmic composition is provided, comprising chlorophyll or bacteriochlorophyll compounds for photodynamic treatment (PDT) of diseases, disorders and conditions associated with corneal or scleral anomalies, such as corneal thinning and scleral stretching.

(Bacterio)chlorophyll photosensitizers for treatment of eye diseases and disorders

Conjugates of porphyrin, chlorophyll and bacteriochlorophyll photosensitizers with RGD-containing peptides or RGD peptidomimetics are provided that are useful for photodynamic therapy (PDT), particularly vascular-targeted PDT (VTP), of tumors and nonneoplastic vascular diseases such as age-related macular degeneration, and for diagnosis of tumors by different techniques.

Conjugates of RGD peptides and (bacterio)chlorophyll photosensitizers

Conjugates of RGD peptides and porphyrin or (bacterio)chlorophyll photosynthesizers and their uses

RGD-chlorophyll and RGD-bacteriochlorophyll conjugates that home and accumulate in necrotic tumor domains much longer than in tumor non-necrotic domains are provided for use in minimally invasive tumor-targeted imaging, tumor-targeted photodynamic therapy, and/or on-line prognosis of necrotic tumors.

RGD-(bacterio)chlorophyll conjugates for photodynamic therapy and Imaging of Necrotic tumors

The invention provides anionic water-soluble tetracyclic and pentacyclic bacteriochlorophyll derivatives (Bchls) containing at least one, preferably two or three, negatively charged groups and/or acidic groups that are converted to negatively charged groups at the physiological pH, preferably Bchls having a group COO&#x3c;&#x2212;&#x3e;, COS&#x3c;&#x2212;&#x3e;, SO3&#x3c;&#x2212;&#x3e;, PO3&#x3c;2&#x2212;&#x3e;, COOH, COSH, SO3H, and/or PO3H2 bound through an ester or amide bond to one or more of the positions 17&#x3c;3&#x3e;, 13&#x3c;3&#x3e;, and 3&#x3c;2&#x3e; of the tetracyclic or pentacyclic Bchl molecule, for photodynamic therapy and diagnosis.

Water-soluble anionic bacteriochlorophyll derivatives and their uses

The invention provides cationic tetracyclic and pentacyclic bacteriochlorophyll derivatives (Bchls) containing at least one positively charged group and/or at least one basic group that is converted to a positively charged group under physiological conditions, preferably Bchls having an onium group derived from a N-containing aliphatic or heterocyclic radical such as ammonium, guanidinium, imidazolium, pyridinium, and the like or a phosphonium, arsonium, oxonium, sulfonium, selenonium, telluronium, stibonium, or bismuthonium group, or a basic group that is converted to such onium groups under physiological conditions, said groups being bound to one or more of the positions 17&#x3c;3&#x3e;, 13&#x3c;3&#x3e; and 3&#x3c;2&#x3e; of the Bchl molecule by ester or amide bond. The Bchls are useful for photodynamic therapy and diagnosis.

Catatonic bacteriochlorophyll derivatives

An online Blood Oxygenation Level-Dependent (BOLD)-magnetic resonance imaging (MRI) method for functional clinical guidance or monitoring a therapeutic modality involving treatment by a sensitizer which, upon excitation by the appropriate sensitizing radiation, initiates local oxygen consumption, comprising: (i) generating a BOLD-weighted MR-image of the target region of interest within the patient's body (time t); (ii) administering said sensitizer to the patient; (iii) irradiating the target region while the patient is subjected to continuous MR imaging; (iv) generating a sole or a plurality of T2* weighted sequential BOLD MR-images during and/or after irradiation (time t); (v) processing the data generated at time tand time t and generating a color-coded difference or ratio map on a pixel by pixel basis; and (vi) analyzing the processed data. The method is preferably applied to photodynamic therapy (PDT).

Sensitized online BOLD-MRI imaging method

Novel C-13-COXR, C-17-COXRand C-13-COXR, C-17-COXRderivatives of chlorophyll and bacteriochlorophyll compounds are provided wherein X is O, S or N and Rand R, the same or different, may be an optionally substituted hydrocarbyl, amino acid, peptide, protein or saccharide radical. The compounds are for use in photodynamic therapy (PDT), for diagnosis of tumors, and for killing cells and infectious agents such as bacteria and virus, both in biological products and in living tissues.

Chlorophyll and bacteriochlorophyll esters, their preparation and pharmaceutical compositions comprising them

Palladium-substituted Bacteriochlorophyll derivatives are administered to a subject suspected of having a tumor and the patient is then irradiated and the fluorescence of the suspected area is measured. A high fluorescence indicates a tumor site. A preferred derivative is Pd-Bacteriopheophorbide a.

Method for tumor diagnosis comprising administering of palladium-substituted bacteriochlorophyll derivatives

Conjugates of chlorophyll (Chl) and bacteriochlorophyll (Bchl) derivatives with amino acids, peptides and proteins are provided by the invention. The amino acid, peptide or protein residue is linked to the 17-propionic acid group of a Chl or Bchl residue directly or through a chain. The conjugates are for use as photosensitizers in photodynamic therapy and in diagnostics of tumors. Conjugation with cell-specific ligands, such as hormones, growth factors or tumor-specific antibodies, will target the Chl or Bchl moiety to the tumor site. Thus, conjugates with melanocyte stimulating hormones are suitable for photodynamic therapy of melanoma tumors.

Chlorophyll and bacteriochlorophyll derivatives, their preparation and pharmaceutical compositions comprising them

Palladium-substituted Bacteriochlorophyll derivatives of formula (I), wherein A represents OH, OR , &mdash;O&mdash;(CH ) &mdash;Y, &mdash;S&mdash;(CH ) &mdash;Y, &mdash;NH&mdash;(CH ) &mdash;Y, &mdash;O&mdash;(CH ) &mdash;NH , &mdash;O&mdash;(CH ) &mdash;OH, &mdash;NH&mdash;(CH ) &mdash; N o, X&mdash;, &mdash;NH0(CH ) &mdash;NH&boxH;BOC or &mdash;N&mdash;(CH &mdash;CH&boxH;CH ) ; wherein R represents Na , K , (Ca ) , (Mg ) , Li , NH , NH &mdash;C(CH OH) NH &mdash;CH &mdash;(CHOH) &mdash;CH OH, NH (CH )&mdash;CH &mdash;(CHOH) &mdash;CH OH or N(C H ) ; R represents H, OH or COOR , wherein R is C -C alkyl or C -C cycloalkl; R represents H, OH or C -C alkyl or alkoxy; n is 1, 2, 3, 4, 5 or 6, Y is &mdash;NR&prime; R&prime; R&prime; , X-wherein R&prime; , R&prime; and R&prime; independently from each other represent &mdash;CH or &mdash;C H ; X is F, Cl, Br or 1, n&prime; is 1, 2, 3 or 4 and their oxidized forms, are useful in the field of photodynamic therapy (PDT).

Palladium-substituted bacteriochlorophyll derivatives and use thereof

The present invention relates to a new method of preparation of metalated bacteriochlorophyll derivatives for use in methods of in vivo photodynamic therapy (PDT) and diagnosis and in vitro photodynamic killing of viruses and microorganisms, and to some novel metal-substituted bacteriochlorophyll derivatives.

Growing community of inventors

Rehovot, Israel

Yoram Salomon