New York Blood Center, Inc.

Hadasit Medical Research Services and Development Company

Hadasit Medical Research and Development Ltd.

Hadasit Medical Research Services and Development Ltd.

Hapio Biotech, Inc.

Habto Biotech, Inc.

Medical Research Services and Development Ltd.

Gerard Marx

Raphael Gorodetsky

Bernard Horowitz

Jinsheng Zou

John Hamman

Novel cell attachment peptides having sequences homologous to specific portions of the carboxy terminal sequence of fibrinogen chains are disclosed. The novel peptides, derived from proteins related to fibrinogen including a peptide adjacent to fibrinogen &#x3b3;-chain C terminus denoted pre-C&#x3b3; possess cell attraction activities, and are useful in pharmaceutical compositions.

Haptotactic peptides

We disclose haptotactic peptides having sequences homologous to specific portions of the carboxy terminal sequence of fibrinogen chains. The peptides derived from fibrinogen pre-C&#x3b3; chain possess activities of cell attraction or cell attachment to a surface to which the peptide is covalently bound.

Haptotactic peprides

This invention is related to a novel peptide consisting of the amino acid sequence of SEQ ID NO:1, and a pharmaceutical composition comprising the peptide thereof.

An applicator for dispensing a first and second component of a biological adhesive, such as fibrin glue. At least one of said components may contain a suspension of fibrin microbeads (FMB) or a suspension of cells. The present invention uses a single supply of pressurized gas to force the components from the applicator using positive fluid pressure and to atomize them into a convergent spray. Another embodiment of the present invention also provides for the endoscopic application of the biological adhesive directly to tissue defects. The application of positive pressure allows precise metering of the components and application of the adhesive, prevents internal coagulation of the fibrin or clogging by suspended particles and reduces waste and contamination of the components.

Fibrin applicator pistol

The present invention provides fibrin microbeads that are biologically active and comprise extensively cross-linked fibrin(ogen), and a method for preparing the fibrin microbeads. The present invention also provides a composition comprising cells bound to the fibrin microbeads, and methods for culturing and separating cells using the fibrin microbeads of the present invention. Finally, the present invention provides methods for transplanting cells and engineering tissue using the fibrin microbeads of the present invention.

Methods of separating cells, transplanting cells and engineering tissue using fibrin microbeads

The present invention provides fibrin nanoparticles having a mean diameter of 200-2000 nm. The present invention provides also methods for preparing fibrin particles of various sizes, including fibrin nanoparticles and fibrin microbeads. The present invention further provides compositions comprising fibrin particles and an agent, wherein the agent is coupled to the amine or carboxy moieties on the surface of the fibrin particles. In addition the present invention provides a composition comprising fibrin nanoparticles and an agent, wherein the agent is admixed with the fibrin nanoparticles. Still further, the present invention provides a method for introducing an agent into a cell, a method for isolating stem and/or progenitor cells from a biological sample, as well as a composition comprising fibrin particles bound to stem and/or progenitor cells.

Fibrin nanoparticles and uses thereof

Fibrin microbeads are prepared containing extensively cross-linked fibrin (ogen) without using glutaraldehyde. The fibrin microbeads are preferably prepared by containing an aqueous solution containing fibrinogen, thrombin and Factor XIII with an oil heated to about 50-80&deg; C. to form an emulsion and mixing the emulsion at 50-80&deg; C. until fibrin microbeads containing extensively cross-linked fibrin (ogen) are obtained. The fibrin microbeads may have a diameter of about 50-200 microns and can contain a bioactive agent. The fibrin microbeads are used for binding cells such as when culturing or separating one cell type from another, or when transplanting cells or engineering tissue.

Fibrin microbeads prepared from fibrinogen, thrombin and factor XIII for binding cells

The present invention provides fibrin microbeads that are biologically active and comprise extensively cross-linked fibrin(ogen) without using glutaraldehyde, and a method for preparing the fibrin microbeads. The present invention also provides a composition comprising cells bound to the fibrin microbeads, and methods for culturing and separating cells using the fibrin microbeads of the present invention. Finally, the present invention provides methods for transplanting cells and engineering tissue using the fibrin microbeads of the present invention.

Fibrin microbeads prepared from fibrinogen, thrombin and factor XIII

An applicator for dispensing a substance comprising first and a second components of any mixture of fluids for either medical or other applications, in an exemplary application, a biological adhesive, such as a fibrin sealant, wherein the applicator comprises a housing having a first dispensing conduit for dispensing the first component and a second dispensing conduit for dispensing the second component. A pressure supply conduit is in communication with the dispensing conduits and both a first reservoir containing the first component, and a second reservoir containing the second component. A cartridge containing a biologically compatible compressed gas may be attached to the pressure supply conduit. The first and second reservoirs may each be provided with a luer fitting to facilitate attachment to a supply of the first component and the second component, respectively. A first pressure regulator, also in communication with the first reservoir, controls the pressure supplied through the pressure supply conduit to the first reservoir and a second pressure regulator, also in communication with the second reservoir, controls the pressure supplied through the pressure supply conduit to the second reservoir. The pressure regulators may be pressure regulating screws or valves, or they may comprise dispensing conduits having various cross sectional areas or reservoir conduits having various cross sectional areas. The applicator dispenses the first and second components, typically a thrombin solution and a fibrinogen solution, in controlled proportions by adjustment of the pressure regulators.

Fibrin sealant glue-gun with insertable compressed gas cartridge and

An applicator for dispensing a first and a second component of a biological adhesive, such as a fibrin sealant, wherein the applicator comprises a housing having a first dispensing conduit for dispensing the first component and a second dispensing conduit for dispensing the second component. A pressure supply conduit is in communication with the dispensing conduits and both a first reservoir containing the first component, and a second reservoir containing the second component. A first pressure regulator, also in communication with the first reservoir, controls the pressure supplied through the pressure supply conduit to the first reservoir and a second pressure regulator, also in communication with the second reservoir, controls the pressure supplied through the pressure supply conduit to the second reservoir. The pressure regulators may be pressure regulating screws or valves, or they may comprise dispensing conduits having various cross sectional areas or reservoir conduits having various cross sectional areas. The applicator dispenses the first and second components, typically a thrombin solution and a fibrinogen solution, in controlled proportions by adjustment of the pressure regulators.

Fibrin sealant glue-gun

The present invention provides a method for activating prothrombin to thrombin in a prothrombin complex composition comprising at least prothrombin, Factors V, VII, IX, and X, and phospholipid, comprising the steps of: (a) cold-incubating the prothrombin complex composition with 2-15 mM of Ca.sup.2+ ions at a pH of 6.5-8.0 and at a temperature of 2.degree.-8.degree. C. until Factor VII contained in the composition is activated; and (b) incubating the cold-incubated composition at a pH of 6.5-8.0 and at a temperature of 10.degree.-25.degree. C. for a period of time sufficient to activate prothrombin contained in the composition to thrombin.

Method for activating prothrombin to thrombin

The present invention describes a biologically compatible bioadhesive sealant composition comprising fibrin glue and liposomes for use in mammals, including humans. Fibrin glue of the invention comprises fibrinogen and thrombin which are mixed together in various modes with liposomes and applied to a site of injury, to a wound, or to a surgical or nonsurgical incision or opening. In accordance with the invention, the liposomes are embedded within the fibrin glue after coagulation has occurred, and may release bioactive substances contained within their aqueous interiors to promote healing and protection during the recovery process. The bioadhesive composition of the invention promises to maintain hemostasis after surgeries and improves upon existing glues or gel formulations due to its complete biological compatibility, its formation in situ, and its provision of bioactive therapeutics via entrapped liposomes directly to the site. Long-lasting biophysical and biomechanical properties as well as therapeutic value are imparted to the fibrin glue components by the liposome component of the composition. The biocompatible fibrin glue and liposome composition is also amenable for fabrication into films, coatings, or membranes for in vitro and in vivo uses.

Biologic bioadhesive compositions containing fibrin glue and liposomes,

Methods of embedding and culturing tissue employing a fibrin glue composition of 2 to 100 mg/ml fibrinogen, 1 to 200 U/ml fibrinogen-activating enzyme, and 1 to 30 mM Ca(II) compound, are disclosed.

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New York, NY, United States of America

Gerard Marx