Immunoaffinity Isolation of Vitamin K-Dependent Proteins
{'Code': '07020000', 'Directorate': {'Abbreviation': 'ENG', 'LongName': 'Directorate For Engineering'}, 'Division': {'Abbreviation': 'CBET', 'LongName': 'Div Of Chem, Bioeng, Env, & Transp Sys'}}
{'SignBlockName': 'Fred G. Heineken', 'PO_EMAI': None, 'PO_PHON': None}
The use of highly pure plasma-derived vitamin K-dependent protein               in anticoagulant therapies necessitates that these protein                      products be devoid of procoagulant cascade proteins.  The                       homologous sequences found in both pro-and anticoagulant vitamin                K-dependent proteins render classical separation processes                      inadequate for production of highly pure vitamin K-dependent                    proteins.  This study employs a combination of classical                        separation and immunoaffinity isolation steps to produce highly                 pure human Protein C from cryopoor plasma and Cohn fraction                     precipitates.  A prepurification-volume reduction step is                       achieved via anion exchange or wheat germ lectin affinity                       chromatography.  Eluate from this step is then subjected to a                   novel monoclonal antibody isolation step.  The monoclonal                       antibodies employed are selected for their ability to bind                      Protein C either in the presence or absence of calcium.  Thus,                  the immunosorbent materials being evaluated form Ab-Protein C                   complexes that are calcium dependent such that gentle elution                   conditions of either calcium or EDTA buffer solutions are                       employed.  This provides for extended longevity of the                          immunosorbent media.  Several crosslinked, beaded-agaroses and                  celluloses are being evaluated as support matrices.  Process                    feasibility is evaluated based upon the degree of recyclability                 of the immunosorbent materials developed.                                                                                                                       It is hoped that a model immunoaffinity isolation process                       technology for vitamin K-dependent plasma proteins will evolve                  from these studies.  The recently demonstrated clinical                         indications for Protein C as well as other anticoagulant vitamin                K-dependents such as Protein S, signals the urgency for the                     development  of isolation technolgy for producing these proteins                at large scale.  Currently, plasma is the only source which can                 meet the kg per annum or greater needs suggested by biochemical                 and clinical studies.  Even with the advent of cost-effective                   genetically engineered versions of these proteins (which could                  become available in the next 5 years), the need for an                          alternative and natural source of these proteins is necessitated                by the immunogenicity that will likely occur with synthetic                     versions of these same proteins.  The availability of plasma-                   derived anticoagulant proteins would help provide an alternative                therapy needed for those cases where immunogenicity for the                     genetically engineered version is a problem.  There is no doubt                 that the same purification technology developed for plasma                      derived proteins will be useful in genetically engineered protein               production.
[{'FirstName': 'William', 'LastName': 'Drohan', 'PI_MID_INIT': 'N', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'William N Drohan', 'EmailAddress': None, 'NSF_ID': '000452465', 'StartDate': '06/01/1988', 'EndDate': None, 'RoleCode': 'Co-Principal Investigator'}, {'FirstName': 'Charles', 'LastName': 'Esmon', 'PI_MID_INIT': 'T', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Charles T Esmon', 'EmailAddress': 'Charles-Esmon@omrf.ouhsc.edu', 'NSF_ID': '000301915', 'StartDate': '06/01/1988', 'EndDate': None, 'RoleCode': 'Co-Principal Investigator'}, {'FirstName': 'Carolyn', 'LastName': 'Orthner', 'PI_MID_INIT': 'L', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Carolyn L Orthner', 'EmailAddress': None, 'NSF_ID': '000319272', 'StartDate': '06/01/1988', 'EndDate': None, 'RoleCode': 'Co-Principal Investigator'}, {'FirstName': 'William', 'LastName': 'Velander', 'PI_MID_INIT': 'H', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'William H Velander', 'EmailAddress': None, 'NSF_ID': '000306656', 'StartDate': '06/01/1988', 'EndDate': None, 'RoleCode': 'Principal Investigator'}]
{'Name': 'Virginia Polytechnic Institute and State University', 'CityName': 'BLACKSBURG', 'ZipCode': '240603359', 'PhoneNumber': '5402315281', 'StreetAddress': '300 TURNER ST NW', 'StreetAddress2': 'STE 4200', 'CountryName': 'United States', 'StateName': 'Virginia', 'StateCode': 'VA', 'CONGRESSDISTRICT': '09', 'CONGRESS_DISTRICT_ORG': 'VA09', 'ORG_UEI_NUM': 'QDE5UHE5XD16', 'ORG_LGL_BUS_NAME': 'VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY', 'ORG_PRNT_UEI_NUM': 'M515A1DKXAN8'}
{'Name': None, 'CityName': None, 'StateCode': None, 'ZipCode': None, 'StreetAddress': None, 'CountryCode': None, 'CountryName': None, 'StateName': None, 'CountryFlag': None, 'CONGRESSDISTRICT': None, 'CONGRESS_DISTRICT_PERF': '""'}
{'Code': '1402', 'Text': 'BIOCHEMICAL & BIOMASS ENG'}
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1988&All=true', 'xml': '8803036.xml'}