Patents by Inventor Dmitri Tolkatchev
Dmitri Tolkatchev 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).
-
Patent number: 10155802Abstract: A locally-activatable bivalent thrombin binding agent is provided having two thrombin binding moieties for non-overlapping sites on a surface of thrombin linked together by a linker. The linker is a polypeptide having 5 to 30 amino acid residues existing in a folded state under an environmental condition where the binding agent is inactive. The linker changes conformation from the folded state to an unfolded state in response to a change in bulk temperature and/or to the presence of hyper-mobile water thereby activating the binding agent. Such locally-activatable thrombin binding agents can be administered systemically while only targeting specific sites of coagulation or inflammation since the thrombin binding agent will only activate at the site where the existence of atherosclerotic plaques has changed the local bulk temperature and/or created hyper-mobile water sufficiently to unfold the linker and activate the binding agent.Type: GrantFiled: April 13, 2012Date of Patent: December 18, 2018Assignee: National Research Council of CanadaInventors: Feng Ni, Ping Xu, Sazzard Hossain, Dmitri Tolkatchev, Kenji Tonan
-
Publication number: 20160168210Abstract: Compounds of interest, for example active pharmaceutical ingredients, probes or inactive carriers, may be delivered to a site of interest by conjugating the compound of interest to a collagen-binding linear hairpin (CBLH) peptide to form a molecule of Formula (I) and then providing the molecule to the site of interest where the CBLH peptide binds to collagen at the site of interest thereby delivering the compound of interest to the site of interest.Type: ApplicationFiled: October 18, 2013Publication date: June 16, 2016Applicant: NATIONAL RESEARCH COUNCIL OF CANADAInventors: Feng NI, Ping XU, Sazzad HOSSAIN, Dmitri TOLKATCHEV, Louis-Philippe RICHER
-
Publication number: 20140113854Abstract: A locally-activatable bivalent thrombin binding agent is provided having two thrombin binding moieties for non-overlapping sites on a surface of thrombin linked together by a linker. The linker is a polypeptide having 5 to 30 amino acid residues existing in a folded state under an environmental condition where the binding agent is inactive. The linker changes conformation from the folded state to an unfolded state in response to a change in bulk temperature and/or to the presence of hyper-mobile water thereby activating the binding agent. Such locally-activatable thrombin binding agents can be administered systemically while only targeting specific sites of coagulation or inflammation since the thrombin binding agent will only activate at the site where the existence of atherosclerotic plaques has changed the local bulk temperature and/or created hyper-mobile water sufficiently to unfold the linker and activate the binding agent.Type: ApplicationFiled: April 13, 2012Publication date: April 24, 2014Applicant: National Research Council of CanadaInventors: Feng Ni, Ping Xu, Sazzard Hossain, Dmitri Tolkatchev, Kenji Tonan
-
Patent number: 8629240Abstract: Peptides are disclosed that are useful for molecular imaging or diagnosis of a disease state, such as cancer, in which clusterin is upregulated.Type: GrantFiled: April 15, 2010Date of Patent: January 14, 2014Assignee: National Research Council of CanadaInventors: Rana Filfil, Dmitri Tolkatchev, Feng Ni, Maureen D. O'Connor-McCourt, Anne E. G. Lenferink
-
Publication number: 20120121507Abstract: Peptides are disclosed that are useful for molecular imaging or diagnosis of a disease state, such as cancer, in which clusterin is upregulated.Type: ApplicationFiled: April 15, 2010Publication date: May 17, 2012Inventors: Rana Filfil, Dmitri Tolkatchev, Feng Ni, Maureen D. O'Connor-McCourt, Anne E. G. Lenferink
-
Patent number: 8063018Abstract: There is provided herein a multivalent binding molecule and uses thereof. The molecule is useful in binding a target under certain conditions and releasing it under other conditions. The molecule has the general formula (1) of BM1-L-(BM2)n (1) wherein, BM1 is a binding moiety 1 having an affinity for site 1 on the target, BM2 is a binding moiety 2 having an affinity for a site other than site 1 on the target, n is 1 or greater, and L is a linker joining BM1 and BM2, said linker being adapted to respond to a change in its environment with a change in conformation and/or flexibility, wherein BM1 and BM2 may be the same or different and are selected such that in use each of the BM1 and BM2 existing separately has a lower binding affinity then the complex of BM1 and BM2 does when they are linked to form the molecule. BM2 may have a single binding region or multiple binding regions with affinity for the target.Type: GrantFiled: June 20, 2005Date of Patent: November 22, 2011Assignee: National Research Council of CanadaInventors: Feng Ni, Dmitri Tolkatchev, Zhengding Su
-
Publication number: 20090137779Abstract: The tetrapeptide Phe-Asn-Pro-Arg (SEQ ID NO: 3) is a structurally-optimized sequence for binding to the active site of thrombin. By conjugating this tetrapeptide or variants thereof to a C-terminal fragment of hirudin, we were able to generate a series of new multivalent inhibitors of thrombin containing only genetically encodable natural amino acids. We found that synergistic binding to both the active site and an exosite of thrombin can be enhanced through substitutions of amino acid residues at the P4, P3 and P3? sites of the active-site directed sequence, Xaa (P4)-Yaa (P3)-Pro (P2)-Arg (P1)-Pro(P1?)-Gln(P2?)-Zaa(P3?). Complementary to rational design, a phage library was constructed to explore further the residue requirements at the P4, P3 and P3? sites for multivalent and optimized bridge-binding.Type: ApplicationFiled: July 15, 2008Publication date: May 28, 2009Inventors: Feng Ni, Dmitri Tolkatchev, Anna Natapova, Anatol Koutychenko
-
Publication number: 20090105116Abstract: There is provided herein a multivalent binding molecule and uses thereof. The molecule is useful in binding a target under certain conditions and releasing it under other conditions. The molecule has the general formula (1) of BM1-L-(BM2)n (1) wherein, BM1 is a binding moiety 1 having an affinity for site 1 on the target, BM2 is a binding moiety 2 having an affinity for a site other than site 1 on the target, n is 1 or greater, and L is a linker joining BM1 and BM2, said linker being adapted to respond to a change in its environment with a change in conformation and/or flexibility, wherein BM1 and BM2 may be the same or different and are selected such that in use each of the BM1 and BM2 existing separately has a lower binding affinity then the complex of BM1 and BM2 does when they are linked to form the molecule. BM2 may have a single binding region or multiple binding regions with affinity for the target.Type: ApplicationFiled: June 20, 2005Publication date: April 23, 2009Inventors: Feng Ni, Dmitri Tolkatchev, Zhengding Su
-
Patent number: 7456152Abstract: The tetrapeptide Phe-Asn-Pro-Arg (SEQ ID NO: 3) is a structurally-optimized sequence for binding to the active site of thrombin. By conjugating this tetrapeptide or variants thereof to a C-terminal fragment of hirudin, we were able to generate a series of new multivalent inhibitors of thrombin containing only genetically encodable natural amino acids. We found that synergistic binding to both the active site and an exosite of thrombin can be enhanced through substitutions of amino acid residues at the P4, P3 and P3? sites of the active-site directed sequence, Xaa (P4)-Yaa (P3)-Pro (P2)-Arg (P1)-Pro(P1?)-Gln(P2?)-Zaa(P3?). Complementary to rational design, a phage library was constructed to explore further the residue requirements at the P4, P3 and P3? sites for multivalent and optimized bridge-binding.Type: GrantFiled: February 27, 2004Date of Patent: November 25, 2008Assignee: National Research Council of CanadaInventors: Feng Ni, Dmitri Tolkatchev, Anna Natapova, Anatol Koutychenko
-
Publication number: 20070042946Abstract: The tetrapeptide Phe-Asn-Pro-Arg is a structurally-optimized sequence for binding to the active site of thrombin. By conjugating this tetrapeptide or variants thereof to a C-terminal fragment of hirudin, we were able to generate a series of new multivalent inhibitors of thrombin containing only genetically encodable natural amino acids. We found that synergistic binding to both the active site and an exosite of thrombin can be enhanced through substitutions of amino acid residues at the P4, P3 and P3? sites of the active-site directed sequence, Xaa(P4)-Yaa(P3)-Pro(P2)-Arg(P1)-Pro(P1?)-Gln(P2?)-Zaa(P3?). Complementary to rational design, a phage library was constructed to explore further the residue requirements at the P4, P3 and P3? sites for multivalent and optimized bridge-binding. Panning of the phage library has led to thrombin-inhibitory peptides possessing strong anti-clotting activities in the low nanomolar range and yet interfering only partially with the catalytic active site of thrombin.Type: ApplicationFiled: February 27, 2004Publication date: February 22, 2007Inventors: Feng Ni, Dmitri Tolkatchev, Anna Natapova, Anatol Koutychenko
-
Publication number: 20050287527Abstract: There is provided a method of quantitatively ranking transient ligand binding to target biomolecules by means of NMR relaxation dispersion profiles. The present invention also relates to a method to identify ligand site obeying two-state and more complex binding behavior in a transient complex of a ligand with a target molecule, still with the use of NMR. There is also provided an efficient method to quantitate fast dissociation rates of ligands containing at least one magnetic nuclei by performing NMR relaxation dispersion experiments at different protein concentrations, enabling the evaluation of populations and exchange rates, and extending the practical applicability of the NMR relaxation dispersion experiments.Type: ApplicationFiled: January 10, 2003Publication date: December 29, 2005Inventors: Feng Ni, Zhengding Su, Ping Xu, Dmitri Tolkatchev, Michael Osborne, Anatol Koutychenko