Claims for Patent: 10,383,958

Summary for Patent: 10,383,958

Title:	Polymalic acid based nanoconjugates for imaging
Abstract:	Nanoconjugates that include a polymalic-based molecular scaffold with one or more imaging moiety and one or more targeting modules attached to the scaffold are provided. Methods of targeting a diseased cell or a diseased tissue in a subject by administering the nanoconjugate are described. Methods of synthesizing the nanoconjugate are also provided.
Inventor(s):	Black; Keith L. (Los Angeles, CA), Ljubimova; Julia (Studio City, CA), Ljubimov; Alexander (Studio City, CA), Holler; Eggehard (Los Angeles, CA)
Assignee:	CEDARS-SINAI MEDICAL CENTER (Los Angeles, CA)
Application Number:	13/441,599
Patent Claims:	1. A method of targeting and imaging a cell or a tissue in a brain of a subject comprising: administering to the subject a composition including a polymalic acid-based molecular scaffold having a plurality of pendant carboxyl groups, at least one imaging moiety, and at least one targeting module, wherein the polymalic acid-based molecular scaffold is a homopolymer, each of the at least one imaging moiety is conjugated to the polymalic acid-based molecular scaffold through one of the plurality of the pendant carboxyl groups, each of the at least one targeting module is conjugated to the polymalic-acid based molecular scaffold through one of the plurality of the pendant carboxyl group, the at least one imaging moiety comprises Gd-DOTA, the at least one targeting module comprises Cetuximab, and the polymalic acid-based molecular scaffold comprises polymalic acid having a molecular weight between 10,000 Daltons and 800,000 Daltons, and from 5% to 30% of the plurality of the pendant carboxyl groups are conjugated to the Gd-DOTA by an ethylene diamine linker, and the composition is capable of crossing a blood-brain barrier after administering to the subject; visualizing the at least one imaging moiety in the brain of the subject by a magnetic resonance imaging technique; and differentially diagnosing a primary brain cancer from a metastatic brain cancer or a non-tumorous lesion in the brain of the subject. 2. The method of claim 1, wherein the metastatic brain cancer is selected from the group consisting of: triple negative breast cancer metastasized to the brain, lung cancer metastasized to the brain, and HER2-positive breast cancer metastasized to the brain. 3. The method of claim 1, wherein the primary brain cancer is glioblastoma. 4. The method of claim 1, wherein each of the at least one targeting module is independently selected from a group consisting of: an antibody, a peptide, a polypeptide, an oligonucleotide, and a therapeutic chemical. 5. The method of claim 1, wherein the at least one targeting module targets a diseased cell or a diseased tissue and the step of administering results in reduction or elimination of at least one symptom of a disease or condition. 6. The method of claim 5 further comprising monitoring an efficiency of treatment of a disease or other condition in the subject comprising: obtaining a first image of the cell or the tissue in the subject after the step of administering at a first time; obtaining a second image of the cell or the tissue after a period of time subsequent to the first time; and comparing the first image and the second image. 7. The method of claim 1 further comprising providing a period of time for accumulation of the composition in a diseased cell or a diseased tissue. 8. The method of claim 4, wherein the antibody specifically binds to a protein selected from the group consisting of: an epidermal growth factor receptor, laminin 411, insulin-like growth factor, transferrin receptor protein, and tumor necrosis factor-alpha. 9. The method of claim 1, wherein differentially diagnosing comprises determining the presence of the primary brain cancer, the metastatic brain cancer or the non-tumorous lesion in the brain of the subject, wherein determining comprises obtaining a first MRI image of the cell or the tissue in the brain of the subject after the step of administering at a first time; measuring the intensity of an MRI signal in the first image; and comparing the intensity of the MRI signal in the first image with the intensity of the MRI signal in a control MRI image of a normal cell or a tissue from a healthy individual, wherein the a difference in the intensity in the MRI signal in the first MRI image relative to the control MRI image is indicative of the presence the primary brain cancer or the metastatic brain cancer. 10. The method of claim 9 further comprising determining a tumor type, wherein determining comprises obtaining a second MRI image of the cell or the tissue a second time after a period subsequent to the first time; measuring the intensity of the MRI signal in the second MRI image; and comparing the intensity of the MRI signal in the first MRI image with the intensity of the MRI signal in the second MRI signal, wherein the intensity of the MRI signal in the second MRI image similar to the intensity of the MRI signal in the first MRI image is indicative of the presence of an EGFR-expressing tumor. 11. The method of claim 10, wherein the EGFR-expressing tumor is at least one tumor selected from the group consisting of: triple negative breast cancer metastasized to the brain, lung cancer metastasized to the brain, and glioblastoma. 12. The method of claim 1, wherein the non-tumorous lesion is caused by infection resulting from impairment of the immune system.

Details for Patent 10,383,958

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2031-04-06
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2031-04-06