Cedars-sinai Medical Center

Ista Pharmaceuticals, Inc.

Advanced Corneal Systems

University of California

Anthony B Nesburn

Vicken H Karageozian

Steven L Wechsler

Hampar L Karageozian

Gabriel Arturo Carpio Aragon

Maria Cristina Kenney

Michael B Gorin

Ezra Maguen

M Cristina Kenney

Jose Luis Gutierrez Flores

Marvin Martinez

Homayon Ghiasi

Keith L Black

John S Yu

Jose L G Flores

Guey-Chuen Perng

Homayan Ghiasi

John Y Park

Lbachir BenMohamed

Maria Christina Kenney

Phillip Baker

Hamper Karageozian

Certain embodiments of the present invention provide immunogenic compositions that comprise one or more peptides having an amino acid sequence selected from the group consisting of NLLTTPKFT and RMLGDVMAV and methods for administering such compositions to a mammal and thereby inducing in the mammal a CD8T cell-dependent protective immunity against an HSV-1 infection, an HSV-2 infection, an HSV-1 condition, an HSV-2 condition, or combinations thereof.

Immunogenic peptides for treatment of herpes simplex virus infection and conditions

A thimerosal-free hyaluronidase preparation wherein the preferred hyaluronidase enzyme is devoid of molecular weight fractions below 40,000 MW, between 60-70,000 MW and above 100,000 MW. Also disclosed is a method for accelerating the clearance of hemorrhagic blood from the vitreous humor of the eye, said method comprising the step of contacting at least one hemorrhage-clearing enzyme (e.g., a &#x3b2;-glucuronidase, matrix metalloproteinase, chondroitinase, chondroitin sulfatase or protein kinase) with the vitreous humor in an amount which is effective to cause accelerated clearance of blood therefrom.

Hyaluronidase preparation for ophthalmic administration and enzymatic methods for accelerating clearance of hemorrhagic blood from the vitreous body of the eye

An enzymatic method is provided for treating ophthalmic disorders of the mammalian eye. Prevention of neovascularization and the increased rate of clearance from the vitreous of materials toxic to retina is accomplished by administering an amount of hyaluronidase effective to liquefy the vitreous humor of the treated eye without causing toxic damage to the eye. Liquefaction of the vitreous humor increases the rate of liquid exchange from the vitreal chamber. This increase in exchange removes those materials and conditions whose presence causes ophthalmological and retinal damage.

Use of hyaluronidase in the manufacture of an ophthalmic preparation for liquefying vitreous humor in the treatment of eye disorders

Disclosed is an HSV-1-derived vector containing a DNA having a functional LAT promoter, or operative fragment thereof, a deletion in both copies of the HSV-1 LAT gene, and a deletion in both copies of the HSV-1 ICP34.5 gene. The HSV-1-derived vectors are non-neurovirulent and do not spontaneously reactivate from latency, and they optionally contain a functional HSV thymidine kinase gene, which can enhance the effectiveness against cancer of drug treatment with gancyclovir or acyclovir. Alternatively, the HSV-1-derived vectors contain at least one transcriptional unit of a LAT promoter sequence operatively linked to a nucleic acid encoding a preselected protein. In some embodiments, the preselected protein is a nucleotide sequence encoding a polypeptide toxic for cells expressing the vector, for example, human interferon-&#x3b3;. Also, disclosed are kits for expressing in a mammalian cell a gene encoding a preselected protein, and mammalian cells containing the HSV-derived vectors.

Herpes simplex virus type 1 (HSV-1)-derived vector for selectively inhibiting malignant cells and for expressing desired traits in malignant and non-malignant mammalian cells

Disclosed is a method of selectively inhibiting the growth of malignant cells in mammals, including humans. The method selectively inhibits the growth of malignant cells of all varieties, and is particularly useful in treating brain tumors and other malignancies of the central nervous system. The method employs HSV-1-derived vectors containing a DNA having a deletion in both copies of the LAT gene and both copies of the ICP34.5 gene of HSV-1. The vectors are delivered to malignant cells either in vivo or in vitro, in accordance with the method. The HSV-1-derived expression vectors are non-neurovirulent and do not spontaneously reactivate from latency, and they optionally contain a functional HSV thymidine kinase gene, which can enhance the effectiveness against cancer of drug treatment with gancyclovir or acyclovir. Alternatively, the HSV-1-derived vectors contain at least one transcriptional unit of a LAT promoter sequence operatively linked to a nucleic acid having a nucleotide sequence encoding a polypeptide toxic for cells expressing the vector, for example, human interferon-&ggr;. A method of expressing in a mammalian cell a gene encoding a preselected protein, a method of treating a genetic defect, and a method of detecting an HSV-1 expressing cell also employ vectors of the present invention that contain at least one transcriptional unit of a constitutive LAT promoter operatively linked to and controlling the transcription of a gene encoding a preselected protein. Also, disclosed are kits for expressing in a mammalian cell a gene encoding a preselected protein, useful for practicing the methods, and mammalian cells containing the HSV-derived vectors.

HERPES SIMPLEX VIRUS TYPE 1 (HSV-1)-DERIVED VECTOR FOR SELECTIVELY INHIBITING MALIGNANT CELLS AND METHODS FOR ITS USE TO TREAT CANCERS AND TO EXPRESS DESIRED TRAITS IN MALIGNANT AND NON-MALIGNANT MAMMALIAN CELLS

An enzymatic method is provided for treating ophthalmic disorders of the mammalian eye. Prevention of neovascularization and the increased rate of clearance from the vitreous of materials toxic to the retina is accomplished by administering an amount of hyaluronidase effective to liquefy the vitreous humor of the treated eye without causing toxic damage to the eye. Liquefaction of the vitreous humor increases the rate of liquid exchange from the vitreal chamber. This increase in exchange removes those materials and conditions whose presence causes ophthalmological and retinal damage.

The invention provide a method for accelerating the clearance of hemorrhagic blood from the vitreous humor of a mammalian eye without producing toxicity to the eye, the method comprising contacting with the vitreous humor an amount of a solution which contains hyaluronidase to provide a dose of at least 1 International Unit of hyaluronidase, the hyaluronidase being in purified form possessing intravitreal hemorrhage-clearing activity and being free from impurities that produce toxicity to the eye.

Hyaluronidase preparation for ophthalmic administration and enzymatic methods for accelerating clearance of hemorrhagic blood from the vireous body of the eye

An Enzyme Orthokeratology method is provided for correcting refractive errors in the eye of a subject mammal. Accelerating reshaping of the cornea is accomplished by administering a corneal hardening amount of a corneal hardening agent to the eye of the subject. Reformation is accomplished under the influence of a rigid contact lens or a series of lenses having a concave curvature that will correct a refractive error. The cornea rapidly reshapes its convex curvature to the concave curvature of the contact lens, rendering the eye emmetropic. The cornea is permitted to &ldquo;harden&rdquo; to retain the new emmetropic shape. After &ldquo;hardening&rdquo; has occurred, the lens rendering the eye emmetropic is removed.

Use of corneal hardening agents in enzymeorthokeratology

The present invention relates to the field of infectious diseases and ophthalmology. More particularly, the invention relates to compositions and methods for vaccination against Herpes Simplex Virus which rely on preparations comprising a mixture of five, six, or seven HSV glycoproteins selected from the group consisting of gB, gC, gD, gE, gG, gH, and gI.

Pharmaceutical composition of herpes simplex virus typ-1 (HSV-1) glycoproteins

A thimerosal-free hyaluronidase is prepared wherein the preferred hyaluronidase is devoid of molecular weight fractions below 40,000 MW, between 60-70,000 MW and above 100,000 MW. Also a method for accelerating the clearance of hemorrhagic blood from the vitreous humor of the eye is carried out by contacting at least one hemorrhage-clearing enzyme (e.g., hyaluronidase, .beta.-glucuronidase, matrix metalloproteinase, chondroitinase, chondroitin sulfatase or protein kinase) with the vitreous humor in an amount which is effective to cause accelerated clearance of blood therefrom.

Method for accelerating clearance of hemorrhagic blood from the vitreous

Pharmaceutical compsition of herpes simplex virus type-1 (HSV-1),

A thimerosal-free hyaluronidase preparation wherein the preferred hyaluronidase enzyme is devoid of molecular weight fractions below 40,000 MW, between 60-70,000 MW and above 100,000 MW. Also disclosed is a method for accelerating the clearance of hemorrhagic blood from the vitreous humor of the eye, comprising the step of contacting at least one hemorrhage-clearing enzyme (e.g., a .beta.-glucuronidase, matrix metalloproteinase, chondroitinase, chondroitin sulfatase or protein kinase) with the vitreous humor in an amount which is effective to cause accelerated clearance of blood therefrom.

Immunotherapy for the treatment of Herpes Simplex Virus eye infections is disclosed. The invention involves a local therapeutic or prophylactic vaccine for the eye, comprising one or more recombinant HSV-1 glycoproteins or proteins, specifically gB and gD, in combination with at least one adjuvant to reduce the incidence of primary HSV-1 infection and/or decrease spontaneous HSV-1 ocular shedding which in turn, controls recurrent corneal disease.

Immunotherapy for recurrent HSV infections

A process for obtaining Herpes Simplex virus type 1 (HSV-1) glycoprotein I (gI) from cells which have been infected or transformed with a recombinant Baculovirus is disclosed. The gI produced is then isolated and purified for use in immunotherapy against HSV infections.

Process for the expression of herpes simplex virus type 1 glycoprotein I

A method for molecularly crosslinking amino acid-containing polymers by photoactivating chemical crosslinkers which have been combined with the polymers. Collagen crosslinked by this method can be used as a bioadhesive for sutureless closures of the skin and eye or as a superhydrated material for contact lenses, moist bandage contact lens, lens or corneal implant material, or as a drug delivery mechanism.

Growing community of inventors

Malibu, CA, United States of America

Anthony B Nesburn