Patents by Inventor Ralph Weissleder
Ralph Weissleder has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
-
Publication number: 20060100529Abstract: We present, in exemplary embodiments of the present invention, a system combining optical imaging technologies with anatomical imaging technologies (e.g., MR, ultrasound). The system can be used for a variety of applications, including, but not limited to, (1) cancer diagnosis and staging; (2) image guidance; and (3) radiation therapy planning. Image guidance may include guiding a biopsy. For example, a prostatectomy potentially has severe side effects, such as impotence and incontinence. Thus, a histologically-confirmed diagnosis, such as one provided from a biopsy, may prevent unnecessary prostatectomy. Image guidance may also include guiding minimal invasive therapy, such as brachytherapy focused ultrasound. The present invention may be used to plan radiation therapy, for example, by detecting, and thus sparing, healthy tissue from radiation exposure.Type: ApplicationFiled: January 27, 2005Publication date: May 11, 2006Inventors: Bogdan Rueckmann, Ralph Gareus, Arne Hengerer, Ralph Weissleder, Wilhelm Durr
-
Publication number: 20050249668Abstract: The invention includes new water-soluble NIR fluorochromes, e.g., for biomedical imaging. The new dyes are highly stable, asymmetric cyanine compounds, characterized by 1) superior chemical stability, 2) excellent optical properties (e.g., high quantum yield), 3) bio-compatibility, 4) conjugatability and 5) ideal in vivo imaging properties. Monoactivated hydroxysuccinimide esters of the new dyes are highly reactive with peptides, metabolites, proteins, peptide-folate conjugates, and other biological macromolecules and affinity ligands, forming stable complexes. Affinity molecules tagged with the new dyes can be used, for example, for imaging of tumors in vivo.Type: ApplicationFiled: March 31, 2003Publication date: November 10, 2005Inventors: Ralph Weissleder, Ching-Shuan Tung, Yuhui Lin
-
Publication number: 20050169843Abstract: The invention relates to activatable imaging probes that includes a chromophore attachment moiety and one or more, e.g., a plurality of, chromophores, such as near-infrared chromophores, chemically linked to the chromophore attachment moiety so that upon activation of the imaging probe the optical properties of the plurality of chromophores are altered. The probe optionally includes protective chains or chromophore spacers, or both. Also disclosed are methods of using the imaging probes for optical imaging.Type: ApplicationFiled: December 22, 2003Publication date: August 4, 2005Inventors: Ralph Weissleder, Ching-Hsuan Tung, Umar Mahmood
-
Publication number: 20050079149Abstract: Hyperbranched dendron (HD) polymers are synthesized using low molecular weight polyethyleneimine (BPEI-L) as a core and used for gene delivery. The obtained polymers display low toxicity and efficient gene delivery at low nitrogen-to-phosphate (N/P) ratios. Using successive attachment of ethyleneimine moieties to a PEI core, the polymer has a lower relative ratio of linear-to-branched structures than in the core PEI. The more extensive branching enables the polymer to condense plasmid DNA into nanostructure complexes with a size of less than or equal to about 100 nm. The complexes are stable and efficient in transfecting cells in the presence of serum. Bioluminescent imaging of in vivo gene expression using a luciferase reporter gene performed in live mice showed gene expression in the liver and in submandibular lymph nodes.Type: ApplicationFiled: March 22, 2004Publication date: April 14, 2005Inventors: Pallab Banerjee, Wilfried Reichardt, Ralph Weissleder, Alexei Bogdanov
-
Publication number: 20040241096Abstract: The invention features methods of detecting enzymatic activity (e.g., in a magnetic resonance image). In general, the methods include: (1) providing a monomeric substrate (e.g., a substrate that is polymerizable in the presence of an enzyme or as a result of an enzyme-catalyzed reaction), having the generic structure X-Y-Z, where X includes a chelator moiety having a chelated paramagnetic or superparamagnetic metal atom or ion, Y includes a linker moiety (e.g., to provide a covalent or non-covalent chemical bond or bonds between X and Z), and Z includes a polymerizing moiety; (2) contacting the substrate with a target tissue, wherein the substrate undergoes polymerization to form a paramagnetic or superparamagnetic polymer, the polymerization being catalyzed by an enzyme in an extracellular matrix or bound to the surfaces of cells of the target tissue; and (3) detecting an increase in relaxivity for the polymer relative to an equivalent amount of unpolymerized substrate.Type: ApplicationFiled: April 30, 2004Publication date: December 2, 2004Applicant: The General Hospital Corporation, a Massachusetts corporationInventors: Alexei Bogdanov, Ralph Weissleder
-
Patent number: 6737247Abstract: The invention features methods of detecting enzymatic activity (e.g., in a magnetic resonance image). In general, the methods include: (1) providing a monomeric substrate (e.g., a substrate that is polymerizable in the presence of an enzyme or as a result of an enzyme-catalyzed reaction), having the generic structure X-Y-Z, where X includes a chelator moiety having a chelated paramagnetic or superparamagnetic metal atom or ion, Y includes a linker moiety (e.g., to provide a covalent or non-covalent chemical bond or bonds between X and Z), and Z includes a polymerizing moiety; (2) contacting the substrate with a target tissue, wherein the substrate undergoes polymerization to form a paramagnetic or superparamagnetic polymer, the polymerization being catalyzed by an enzyme in an extracellular matrix or bound to the surfaces of cells of the target tissue; and (3) detecting an increase in relaxivity for the polymer relative to an equivalent amount of unpolymerized substrate.Type: GrantFiled: October 19, 2001Date of Patent: May 18, 2004Assignee: The General Hospital CorporationInventors: Alexei Bogdanov, Ralph Weissleder
-
Publication number: 20040015062Abstract: This invention relates to a fluorescence-mediated molecular tomographic imaging system, designed to detect near-infrared fluorescence activation in deep tissues. The system can use targeted fluorescent molecular probes or highly sensitive activatable fluorescence molecular probes. Such probes add molecular specificity and yield high fluorescence contrast, to allow early detection and molecular target assessment of diseased tissue, such as cancers, in vivo. The new tomographic imaging system enables three-dimensional localization in deep tissues and quantitation of molecular probes.Type: ApplicationFiled: May 22, 2003Publication date: January 22, 2004Inventors: Vasilis Ntziachristos, Ralph Weissleder
-
Publication number: 20030219383Abstract: An intramolecularly-quenched, near infrared fluorescence probe that emits substantial fluorescence only after interaction with a target tissue (i.e., activation) is disclosed. The probe includes a polymeric backbone and a plurality of near infrared fluorochromes covalently linked to the backbone at fluorescence-quenching interaction-permissive positions separable by enzymatic cleavage at fluorescence activation sites. The probe optionally includes protective chains or fluorochrome spacers, or both. Also disclosed are methods of using the intramolecularly-quenched, near infrared fluorescence probes for in vivo optical imaging.Type: ApplicationFiled: February 7, 2003Publication date: November 27, 2003Applicant: The General Hospital Corporation, a Massachusetts corporationInventors: Ralph Weissleder, Ching-Hsuan Tung, Umar Mahmood, Lee Josephson, Alexei Bogdanov
-
Patent number: 6615063Abstract: This invention relates to a fluorescence-mediated molecular tomographic imaging system, designed to detect near-infrared fluorescence activation in deep tissues. The system can use targeted fluorescent molecular probes or highly sensitive activatable fluorescence molecular probes. Such probes add molecular specificity and yield high fluorescence contrast, to allow early detection and molecular target assessment of diseased tissue, such as cancers, in vivo. The new tomographic imaging system enables three-dimensional localization in deep tissues and quantitation of molecular probes.Type: GrantFiled: November 27, 2000Date of Patent: September 2, 2003Assignee: The General Hospital CorporationInventors: Vasilis Ntziachristos, Ralph Weissleder
-
Patent number: 6592847Abstract: An intramolecularly-quenched, near infrared fluorescence probe that emits substantial fluorescence only after interaction with a target tissue (i.e., activation) is disclosed. The probe includes a polymeric backbone and a plurality of near infrared fluorochromes covalently linked to the backbone at fluorescence-quenching interaction-permissive positions separable by enzymatic cleavage at fluorescence activation sites. The probe optionally includes protective chains or fluorochrome spacers, or both. Also disclosed are methods of using the intramolecularly-quenched, near infrared fluorescence probes for in vivo optical imaging.Type: GrantFiled: June 27, 2000Date of Patent: July 15, 2003Assignee: The General Hospital CorporationInventors: Ralph Weissleder, Ching-Hsuan Tung, Umar Mahmood, Lee Josephson, Alexei Bogdanov
-
Publication number: 20030092029Abstract: The present invention provides novel compositions of binding moiety-nanoparticle conjugates, aggregates of these conjugates, and novel methods of using these conjugates, and aggregates. The nanoparticles in these conjugates can be magnetic metal oxides, either monodisperse or polydisperse. Binding moieties can be, e.g., oligonucleotides, polypeptides, or polysaccharides. Oligonucleotide sequences are linked to either non-polymer surface functionalized metal oxides or with functionalized polymers associated with the metal oxides. The novel compositions can be used in assays for detecting target molecules, such as nucleic acids and proteins, in vitro or as magnetic resonance (MR) contrast agents to detect target molecules in living organisms.Type: ApplicationFiled: June 6, 2002Publication date: May 15, 2003Inventors: Lee Josephson, Ralph Weissleder, J. Manuel Perez
-
Publication number: 20030044353Abstract: The invention relates to activatable imaging probes that includes a chromophore attachment moiety and one or more, e.g., a plurality of, chromophores, such as near-infrared chromophores, chemically linked to the chromophore attachment moiety so that upon activation of the imaging probe the optical properties of the plurality of chromophores are altered. The probe optionally includes protective chains or chromophore spacers, or both. Also disclosed are methods of using the imaging probes for optical imaging.Type: ApplicationFiled: January 4, 2002Publication date: March 6, 2003Inventors: Ralph Weissleder, Ching-Hsuan Tung, Umar Mahmood
-
Patent number: 6511967Abstract: Cells can be imaged, e.g., in vivo, in an animal or human subject by introducing into the cells a nucleic acid encoding an internalizing receptor, administering to the animal or human subject a reporter complex including one or more receptor-specific reporter moieties linked to one or more reporter groups, such as magnetic particles, and detecting the reporter complex, e.g., using magnetic resonance imaging, and thus detecting the cells. If a specific gene is expressed in a constant, known ratio compared to expression of the receptor, the expression of that gene can be monitored by detecting the reporter complex, and thus, concomitantly, expression of the internalizing receptor and the specific gene.Type: GrantFiled: April 21, 2000Date of Patent: January 28, 2003Assignee: The General Hospital CorporationInventors: Ralph Weissleder, James P. Basilion, Ennio Antonio Chiocca
-
Publication number: 20020142297Abstract: Described are short peptide sequences, termed recombinant peptide chelates (RPCs), and the imaging marker genes that encode them. The RPCs can be expressed in parallel with the expression of any other desired gene (e.g., a therapeutic gene), and used to easily confirm the expression of the therapeutic gene product. The RPCs are expressed in the cell or on the cell surface concurrently with the therapeutic gene product, and can be assayed by standard imaging techniques.Type: ApplicationFiled: December 18, 2000Publication date: October 3, 2002Applicant: The General Hospital Corporation, a Massachusetts corporationInventors: Alexei A. Bogdanov, Ralph Weissleder, Maria Simonova
-
Publication number: 20020127629Abstract: The invention features methods of detecting enzymatic activity (e.g., in a magnetic resonance image). In general, the methods include: (1) providing a monomeric substrate (e.g., a substrate that is polymerizable in the presence of an enzyme or as a result of an enzyme-catalyzed reaction), having the generic structure X-Y-Z, where X includes a chelator moiety having a chelated paramagnetic or superparamagnetic metal atom or ion, Y includes a linker moiety (e.g., to provide a covalent or non-covalent chemical bond or bonds between X and Z), and Z includes a polymerizing moiety; (2) contacting the substrate with a target tissue, wherein the substrate undergoes polymerization to form a paramagnetic or superparamagnetic polymer, the polymerization being catalyzed by an enzyme in an extracellular matrix or bound to the surfaces of cells of the target tissue; and (3) detecting an increase in relaxivity for the polymer relative to an equivalent amount of unpolymerized substrate.Type: ApplicationFiled: October 19, 2001Publication date: September 12, 2002Inventors: Alexei Bogdanov, Ralph Weissleder
-
Patent number: 6284220Abstract: Nucleic acid-imaging compositions and methods for noninvasive imaging of a nucleic acid introduced into somatic tissues of an animal or human are disclosed. The noninvasive imaging enables quantitative assessment of the biodistribution of the introduced nucleic acid. The disclosed imaging compounds include a base-binding moiety, a phosphate-binding moiety, and a metal-binding moiety. A chelated metal is non-invasively detected for imaging by radioactivity or magnetic resonance.Type: GrantFiled: June 3, 1999Date of Patent: September 4, 2001Assignee: The General Hospital CorporationInventors: Alexei Bogdanov, Ching-Hsuan Tung, Ralph Weissleder
-
Patent number: 6083486Abstract: An intramolecularly-quenched, near infrared fluorescence probe that emits substantial fluorescence only after interaction with a target tissue (i.e., activation) is disclosed. The probe includes a polymeric backbone and a plurality of near infrared fluorochromes covalently linked to the backbone at fluorescence-quenching interaction-permissive positions separable by enzymatic cleavage at fluorescence activation sites. The probe optionally includes protective chains or fluorochrome spacers, or both. Also disclosed are methods of using the intramolecularly-quenched, near infrared fluorescence probes for in vivo optical imaging.Type: GrantFiled: May 14, 1998Date of Patent: July 4, 2000Assignee: The General Hospital CorporationInventors: Ralph Weissleder, Ching-Hsuan Tung, Umar Mahmood, Lee Josephson, Alexei Bogdanov
-
Patent number: 5871710Abstract: A biocompatible graft co-polymer adduct including a polymeric carrier, a protective chain linked to the polymeric carrier, a reporter group linked to the carrier or to the carrier and the protective chain, and a reversibly linked Pt(II) compound. The invention also relates to a method of treating a disease in a patient, particularly cancer, by administering to the patient a therapeutically effective amount of the adduct, and may include scanning the patient using an imaging technique which can provide a visible image of the distribution of the adduct.Type: GrantFiled: October 28, 1996Date of Patent: February 16, 1999Assignee: The General Hospital CorporationInventors: Alexei Bogdanov, Ralph Weissleder, Thomas J. Brady
-
Patent number: 5605672Abstract: The invention features a method of blood pool imaging which utilizes an imaging agent which can be easily labelled with a radioactive isotope and injected into a patient. The imaging agent is a covalent conjugate of a polymeric carrier, protective groups, and chelating groups. The imaging agent is preferably provided in the form of a blood pool imaging composition, which includes an imaging agent of the invention, a buffer and a reducing compound. A radioactive isotope is added to the blood pool imaging composition to label the imaging agent, and the composition containing the labelled imaging agent is injected intravenously into a patient.Type: GrantFiled: June 9, 1993Date of Patent: February 25, 1997Assignee: The General Hospital CorporationInventors: Alexei A. Bogdanov, Ralph Weissleder, Thomas J. Brady, Ronald Callahan
-
Patent number: 5514379Abstract: Biocompatible, biodegradable, hydrogels are prepared from a backbone bonded to a cross-linking agent. Suitable backbones include proteins and polysaccharides, e.g,, albumin, polymannuronic acid, or polygalacturonic acid. Suitable cross-linking agents include polyvalent derivatives of polyethylene or polyalkylene glycol. These hydrogel compositions may be loaded with diagnostic labels, e.g,, radiopaque, paramagnetic, or superparamagnetic materials, or therapeutic drugs, e.g., chemotherapeutic drugs, antibiotics, or cells that produce therapeutic agents. This invention also relates to methods of use of such hydrogels for imaging during interventional procedures of a patient.Type: GrantFiled: August 7, 1992Date of Patent: May 7, 1996Assignee: The General Hospital CorporationInventors: Ralph Weissleder, Alexei Bogdanov