Patents Assigned to Prolinx, Inc.
  • Publication number: 20040072203
    Abstract: This invention provides methods for purifying nucleic acids, in particular primer extension products such as those obtained in nucleic acid sequencing reactions. The methods involve the use of a primer to which is attached a string of arylboronic acid moieties. After extension of the primer using a polymerase, the primer extension-products are complexed with a solid support to which is attached an arylboronic acid complexing moiety. The resulting complex is separated from the reaction mixture, washed, and the primer extension products are dissociated from the solid support. The primer extension products are obtained in a form particularly suitable for loading directly on a capillary electrophoresis apparatus.
    Type: Application
    Filed: April 16, 2003
    Publication date: April 15, 2004
    Applicant: Prolinx, Inc.
    Inventors: Connie Kim Dix, Karin A. Hughes, Robert J. Kaiser, Mark L. Stolowitz
  • Patent number: 6630577
    Abstract: A reagent having the general formula of General Formula I: wherein group Z comprises a spacer selected from an aliphatic chain up to about 6 carbon equivalents in length, an unbranched aliphatic chain of from about 6 to 18 carbon equivalents in length with at least one of an intermediate amide and a disulfide moiety, and a polyethylene glycol chain of from about 3 to 12 carbon equivalents in length; wherein group R is an electrophilic or nucleophilic moiety suitable for reaction of the reagent with a biologically active species; and wherein group Q is one of nothing at all, an amide, a methyl amide, a methylene, an ether, a thioether, a methyl ether, and a methyl thioether moiety. Also, a conjugate, a bioconjugate and a method of conjugating.
    Type: Grant
    Filed: June 4, 2001
    Date of Patent: October 7, 2003
    Assignee: Prolinx, Inc.
    Inventors: Mark L. Stolowitz, Guisheng Li, Jean P. Wiley
  • Patent number: 6462179
    Abstract: Reagents suitable for the modification of a bioactive species for the purpose of incorporating one or more phenyldiboronic acid (PDBA) moieties for subsequent conjugation to a different (or the same) bioactive species having one or more pendant boronic compound complexing moieties of the general formula of General Formula I, wherein group R is a reactive electrophilic or nucleophilic moiety suitable for reaction of the PDBA reagent with a bioactive species. Group Z is a spacer selected from a saturated or unsaturated chain up to about 0 to 6 carbon equivalents in length, an unbranched saturated or unsaturated chain of from about 6 to 18 carbon equivalents in length with at least one intermediate amide or disulfide moiety, and a polyethylene glycol chain of from about 3 to 12 carbon equivalents in length. Group Q is a linkage that includes one of amide, ether and thioether moieties.
    Type: Grant
    Filed: July 25, 2000
    Date of Patent: October 8, 2002
    Assignee: Prolinx, Inc.
    Inventors: Mark L. Stolowitz, Edward A. Kesicki, Kevin P. Lund, Karin A. Hughes
  • Patent number: 6414136
    Abstract: This invention provides methods for removing unincorporated fluorescent dye-labeled molecules from a mixture that includes fluorescently-labeled polynucleotides and the unincorporated fluorescent dye-labeled molecules. The methods involve adsorbing the unincorporated fluorescent dye-labeled molecules into a plurality of particles that are made up of one or more porous hydrophobic materials that are encapsulated in a hydrophilic matrix.
    Type: Grant
    Filed: May 3, 2000
    Date of Patent: July 2, 2002
    Assignee: Prolinx, Inc.
    Inventors: Douglas A. Spicer, Karin A. Hughes, Robert J. Kaiser, James E. Mahoney, Amy L. Springer, Mark L. Stolowitz, Carl H. D. Weissman
  • Patent number: 6414122
    Abstract: Embodiments include reagents to modify a bioactive species for incorporating a bifunctional boronic compound complexing moiety for subsequent conjugation to a different or same bioactive species having pendant phenylboronic acid moieties of General Formula I, wherein group R is an electrophilic or nucleophilic moiety suitable for reaction of the putative bifunctional boronic compound complexing reagent with a bioactive species, wherein group R2 is selected from one of H and OH moieties, and wherein group R3 is selected from one of an alkyl and a methylene bearing an electronegative substituent. Group Z is a spacer selected from (CH2)n and CH2O(CH2CH2O)n2, wherein n is an integer of from 1 to 5, and wherein n2 is an integer of from 1 to 4. Group Z2 and Z3 is a spacer and need not be the same.
    Type: Grant
    Filed: August 29, 2000
    Date of Patent: July 2, 2002
    Assignee: Prolinx, Inc.
    Inventors: Clarence N. Ahlem, Robert J. Kaiser, Kevin P. Lund, Mark L. Stolowitz
  • Patent number: 6156884
    Abstract: Reagents suitable for the modification of a bioactive species for the purpose of incorporating a bifunctional boronic compound complexing moiety for subsequent conjugation to a different (or the same) bioactive species having pendant phenylboronic acid moieties of General Formula 1, ##STR1## wherein group R is an electrophilic or nucleophilic moiety suitable for reaction of the putative bifunctional boronic compound complexing reagent with a bioactive species, wherein group R.sub.2 is selected from one of H and OH moieties, and wherein group R.sub.3 is selected from one of an alkyl and a methylene bearing an electronegative substituent. Group Z is a spacer selected from (CH.sub.2).sub.n and CH.sub.2 O(CH.sub.2 CH.sub.2 O).sub.n.sbsb.2, wherein n is an integer of from 1 to 5, and wherein n.sub.2 is an integer of from 1 to 4. Each of group Z.sub.2 and Z.sub.3 is a spacer selected from CH.sub.2 Ar, CH.sub.2 CONHCH.sub.2 Ar, CH.sub.2 CONH(CH.sub.2).sub.n.sbsb.3 CO--NHCH.sub.2 Ar, and (CH.sub.2).sub.n.sbsb.
    Type: Grant
    Filed: December 29, 1998
    Date of Patent: December 5, 2000
    Assignee: Prolinx, Inc.
    Inventors: Clarence N. Ahlem, Robert J. Kaiser, Kevin P. Lund, Mark L. Stolowitz
  • Patent number: 6124471
    Abstract: Reagents suitable for the modification of a bioactive species for the purpose of incorporating one or more phenyldiboronic acid (PDBA) moieties for subsequent conjugation to a different (or the same) bioactive species having one or more pendant boronic compound complexing moieties of the general formula of General Formula I, ##STR1## wherein group R is a reactive electrophilic or nucleophilic moiety suitable for reaction of the PDBA reagent with a bioactive species. Group Z is a spacer selected from a saturated or unsaturated chain up to about 0 to 6 carbon equivalents in length, an unbranched saturated or unsaturated chain of from about 6 to 18 carbon equivalents in length with at least one intermediate amide or disulfide moiety, and a polyethylene glycol chain of from about 3 to 12 carbon equivalents in length. Group Q is a linkage that includes one of amide, ether and thioether moieties.
    Type: Grant
    Filed: September 28, 1999
    Date of Patent: September 26, 2000
    Assignee: Prolinx, Inc.
    Inventors: Mark L. Stolowitz, Edward A. Kesicki, Kevin P. Lund, Karin A. Hughes
  • Patent number: 6075126
    Abstract: Boron compound complexing reagents, boron compound complexes, and methods of synthesizing these reagents and complexes are disclosed. These reagents and complexes include those shown in General Formula CIII, General Formula CIV, and General Formula CVI. In one embodiment, the reagents of General Formula CIII may be used to produce, after condensation with a bioactive species (BAS), the reagent of General Formula CIV. The reagent of General Formula CIV may be used to form a complex with a boron compound, such as a complex shown in General Formula CVI.
    Type: Grant
    Filed: August 21, 1998
    Date of Patent: June 13, 2000
    Assignee: Prolinx, Inc.
    Inventors: Mark L. Stolowitz, Edward A. Kesicki, Kevin P. Lund, Karin A. Hughes
  • Patent number: 6008406
    Abstract: The present invention relates to novel class of phenylboronic acid complexing reagents useful for the preparation of bioconjugates, and the method of making and using such reagents. In the present invention, in the place of prior art Avidin-Biotin and Digoxigenin-anti-Digoxigenin systems, phenylboronic acid complexing reagents are utilized in conjunction with phenylboronic acid reagents (many of which are known in the prior art) to facilitate chemical conjugation without the use of intermediary biological macromolecules. Reagents suitable for the modification of a bioactive species for the purpose of incorporating a phenylboronic acid complexing moiety for subsequent conjugation to a different bioactive species having pendant phenylboronic acid moieties are of General Formula I or General Formula II. ##STR1## wherein group X is selected from either H, OH, NH.sub.2, NHCH.sub.3, NHOH and NHOCH.sub.
    Type: Grant
    Filed: February 25, 1997
    Date of Patent: December 28, 1999
    Assignee: Prolinx, Inc.
    Inventor: Mark L. Stolowitz
  • Patent number: 5877297
    Abstract: Boron compound completing reagents, intermediate reagents of those reagents and methods of synthesizing these reagents. These reagents, including those shown as General Formula CII may be used, after further reactions described herein, to complex with boronic compounds, such as phenylboronic acid or derivatives thereof. ##STR1## In one embodiment, group Z comprises a spacer selected from a saturated or unsaturated chain up to about 0 to 6 carbon equivalents in length, an unbranched saturated or unsaturated chain of from about 6 to 18 carbon equivalents in length with at least one of intermediate amide and disulfide moieties, and a polyethylene glycol chain of from 3 to 12 carbon equivalents in length; group R.sub.2 is one of an alkyl and a methylene with an electronegative moiety; and BAS is a biologically active species.
    Type: Grant
    Filed: October 22, 1997
    Date of Patent: March 2, 1999
    Assignee: Prolinx, Inc.
    Inventors: Mark L. Stowolitz, Robert J. Kaiser, Kevin P. Lund
  • Patent number: 5872224
    Abstract: Boron compound complexing reagents, boron compound complexes, and methods of synthesizing these reagents and complexes are disclosed. These reagents and complexes include those shown in General Formula CIV, and General Formula CVI. In one embodiment, the reagent of General Formula CIV may be used to form a complex with a boron compound, such as a complex shown in General Formula CVI. ##STR1## In one embodiment, group Z comprises a spacer selected from a saturated or unsaturated chain of up to about 6 carbon equivalents in length, an unbranched saturated or unsaturated chain of from about 6 to 18 carbon equivalents in length with at least one of intermediate amide and disulfide moieties, and a polyethylene glycol chain of from about 3 to 12 carbon equivalents in length; group R.sub.3 is selected from one of an H, an alkyl, and a methylene or ethylene moiety with an electronegative substituent; and BAS and BAS* are biologically active species.
    Type: Grant
    Filed: October 22, 1997
    Date of Patent: February 16, 1999
    Assignee: Prolinx, Inc.
    Inventors: Mark L. Stolowitz, Robert J. Kaiser, Kevin P. Lund
  • Patent number: 5869623
    Abstract: Boron compound complexing reagents, intermediate reagents of those reagents, and methods of synthesizing these reagents are disclosed. These reagents, including those shown as General Formula II may be used, after further reactions described herein, to complex with boronic compounds, such as phenylboronic acid or derivatives thereof. ##STR1## In one embodiment, group Z comprises a spacer selected from a saturated or unsaturated chain of up to about 6 carbon equivalents in length, an unbranched saturated or unsaturated chain from about 6 to 18 carbon equivalents in length with at least one intermediate amide or disulfide moieties, and a polyethylene glycol chain of from about 3 to 12 carbon equivalents in length; group R.sub.2 is one of an alkyl and a methylene group with an electronegative moiety; and BAS is a biologically active species.
    Type: Grant
    Filed: October 22, 1997
    Date of Patent: February 9, 1999
    Assignees: Systemix, Prolinx, Inc.
    Inventors: Mark L. Stolowitz, Robert J. Kaiser, Kevin P. Lund, Steven M. Torkelson
  • Patent number: 5859210
    Abstract: Boron compound complexing reagents, boron compound complexes, and methods of synthesizing these reagents and complexes are disclosed. These reagents and complexes include those shown in General Formula IV and General Formula VI. In one embodiment, the reagent of General Formula IV may be used to form a complex with a boron compound, such as a complex shown in General Formula VI. ##STR1## In one embodiment, group Z comprises a spacer selected from a saturated or unsaturated chain of up to about 6 carbon equivalents in length, an unbranched saturated or unsaturated chain of from about 6 to 18 carbon equivalents in length with at least one of intermediate amide or disulfide moieties, and a polyethylene glycol chain of from about 3 to 12 carbon equivalents in length; group R.sub.3 is selected from one of an H, an alkyl, and a methylene or ethylene moiety with an electronegative substituent; and BAS and BAS* are biologically active species.
    Type: Grant
    Filed: October 22, 1997
    Date of Patent: January 12, 1999
    Assignees: Prolinx, Inc., Systemix
    Inventors: Mark L. Stowolitz, Robert J. Kaiser, Kevin P. Lund, Steven M. Torkelson
  • Patent number: 5852178
    Abstract: A new class of phenylboronic acid complexing reagents are provided capable of binding with phenylboronic acids is disclosed having one of the following structures: ##STR1## wherein group X is selected from H, CH.sub.3 and C.sub.6 H.sub.5 ; and groups Y and Z are selected from O and CH.sub.2 ; group Q is a spacer which is from 2 to 12 carbon equivalents in length, and which may contain intermediate amide and/or ether functionalities; and group R is a reactive electrophilic moiety suitable for conjugation of a phenylboronic acid complexing reagent with a biological macromolecular species, low molecular weight species or solid phase support having a reactive pendant nucleophilic moiety. The phenylboronic acid complexing reagents are utilized in conjunction with phenylboronic acid reagents to facilitate chemical conjugation without the use of intermediary biological macromolecules. The method of making and using such reagents is also disclosed.
    Type: Grant
    Filed: December 22, 1995
    Date of Patent: December 22, 1998
    Assignee: Prolinx, Inc.
    Inventor: Mark L. Stolowitz
  • Patent number: 5847192
    Abstract: Boron compound complexing reagents and methods of synthesizing these reagents are disclosed. These reagents, including those shown as General Formula I and General Formula II may be used, after further reactions described herein, to complex with boronic compounds, such as phenylboronic acid or derivatives thereof.
    Type: Grant
    Filed: August 5, 1996
    Date of Patent: December 8, 1998
    Assignees: Prolinx, Inc., Systemix
    Inventors: Mark L. Stolowitz, Robert J. Kaiser, Kevin P. Lund, Steven M. Torkelson
  • Patent number: 5837878
    Abstract: Boron compound complexing reagents, boron compound complexes, and methods of synthesizing these reagents and complexes are disclosed. These reagents and complexes include those shown in General Formula CIII, General Formula CIV, and General Formula CVI. In one embodiment, the reagents of General Formula CIII may be used to produce, after condensation with a bioactive species (BAS), the reagent of General Formula CIV. The reagent of General Formula CIV may be used to form a complex with a boron compound, such as a complex shown in General Formula CVI.
    Type: Grant
    Filed: August 5, 1996
    Date of Patent: November 17, 1998
    Assignee: Prolinx, Inc.
    Inventors: Mark L. Stolowitz, Robert J. Kaiser, Kevin P. Lund
  • Patent number: 5777148
    Abstract: Boron compound complexing reagents, intermediate reagents of those reagents and methods of synthesizing these reagents are disclosed. These reagents, including those shown as General Formula I and General Formula II may be used, after further reactions described herein, to complex with boronic compounds, such as phenylboronic acid or derivatives thereof.
    Type: Grant
    Filed: August 5, 1996
    Date of Patent: July 7, 1998
    Assignee: Prolinx, Inc.
    Inventors: Mark L. Stowolitz, Robert J. Kaiser, Kevin P. Lund
  • Patent number: 5744627
    Abstract: Boron compound complexing reagents, boron compound complexes, and methods of synthesizing these reagents and complexes are disclosed. These reagents and complexes include those shown in General Formula III, General Formula IV, and General Formula VI. In one embodiment, the reagents of General Formula III may be used to produce, after condensation with a bioactive species (BAS), the reagent of General Formula IV. The reagent of General Formula IV may be used to form a complex with a boron compound, such as a complex shown in General Formula VI.
    Type: Grant
    Filed: August 5, 1996
    Date of Patent: April 28, 1998
    Assignees: Prolinx, Inc., Systemix
    Inventors: Mark L. Stowolitz, Robert J. Kaiser, Kevin P. Lund, Steven M. Torkelson
  • Patent number: 5688928
    Abstract: The present invention relates to a novel class of phenylboronic acid complexing reagents useful for the preparation of bioconjugates, and the method of making and using such reagents. In the present invention, in the place of prior art Avidin-Biotin and Digoxigenin-anti-Digoxigenin systems, phenylboronic acid complexing reagents are utilized in conjunction with phenylboronic acid reagents (many of which are known in the prior art) to facilitate chemical conjugation without the use of intermediary biological macromolecules. Reagents suitable for the modification of bioactive species for the purpose of incorporating a phenylboronic acid complexing moiety for subsequent conjugation to a different bioactive species having pendant phenylboronic acid moieties are of General Formula I or General Formula II. ##STR1## wherein group X is selected from either H, OH, NH.sub.2, NHCH.sub.3, NHOH and NHOCH.sub.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: November 18, 1997
    Assignee: Prolinx, Inc.
    Inventor: Mark L. Stolowitz
  • Patent number: 5677431
    Abstract: The present invention relates to a novel class of phenylboronic acid bioconjugate complexes derived from aminosalicylic acid, and the method of making and using such bioconjugate complexes. The bioconjugate complexes are in the form of the following general formulas; ##STR1## wherein group X is selected from the group consisting of O, NH, N-alkyl, NC.sub.6 H.sub.5, N-aryl, NCH.sub.2 -aryl, NCH.sub.2 CH.sub.2 OH, NCOCH.sub.2 CH.sub.2 OH, NOH, NO-alkyl and NOCH.sub.2 -aryl, wherein alkyl denotes a hydrocarbon moiety of from 1 to 4 carbons in length and which may be linear or branched, wherein aryl is selected from the group consisting of an aromatic ring, a substituted aromatic ring and a fused aromatic ring,wherein group Y is selected from the group consisting of O, S, NH, N-alkyl, N-aryl and NCH.sub.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: October 14, 1997
    Assignee: Prolinx, Inc.
    Inventor: Mark L. Stolowitz