# US 6,174,530 B1 · Homogeneous polyoxime compositions and their preparation by parallel assembly > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 6,174,530 B1 - Document ID: US6174530B1 - Status: Granted - Kind: B1 - Application number: 08/114,877 - Filed: 1993-08-31 - Granted: 2001-01-16 - Earliest claimed: 1993-05-05 - Assignees: Gryphon Sciences - Inventors: Keith Rose; Robin Ewart Offord - Web page: https://patentgrep.com/patent/US6174530B1 ## CPC - C07K 1/1077: {by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids} - A61K 47/59: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes - A61P 37/04: Immunostimulants - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Provided by this invention are essentially homogeneous, defined compositions of matter comprising a baseplate structure having a plurality of oxime bonds, wherein each oxime bond links a specifically active molecule to the baseplate. Also provided are novel baseplates having a plurality of oxime forming complementary reactive groups and novel specifically reactive molecules having an oxime forming complementary reactive group. Also provided by this invention are methods of preparing these novel compositions of matter by chemoselectively ligating via oxime bond formation a complementary orthogonal reactive group on the baseplate to a complementary reactive orthogonal group on a specifically active molecule. Methods of using these defined compositions of matter as well as pharmaceutical compositions comprising these defined compositions of matter and methods of their use are also provided by this invention. ## Claims ### Claim 1 A homogeneous polyoxime composition, in which polyoxime molecules present in said composition comprise a first organic baseplate molecule linked via a plurality of at least three oxime linkages to said plurality of second organic molecules, said oxime linkages being formed by reaction of an orthogonal reactive group on each said second organic molecule with a complementary orthogonal reactive group on said baseplate, wherein said orthogonal reactive group and said complementary orthogonal reactive group are selected from the group consisting of an aldehyde group, a keto group and an amino-oxy group, as appropriate for complementarity, wherein said second organic molecules are identical in structure, wherein said at least three complementary orthogonal reactive groups on said baseplate are identical groups and wherein said first organic baseplate molecule is other than a heterogeneous antibody glycoprotein preparation modified by chemical or enzymatic oxidation of sugar residues. ### Claim 2 (depends on 1) The composition of claim 1, wherein said baseplate is formed at least in part from amino acid residues. ### Claim 3 (depends on 1) The composition of claim 1, wherein said complementary orthogonal reactive group on said baseplate comprises an aldehyde group. ### Claim 4 (depends on 1) The composition of claim 1, wherein said complementary orthogonal reactive group on said baseplate comprises amino-oxy-acetyl. ### Claim 5 (depends on 1) The composition of claim 1, wherein said orthogonal reactive group in said second organic molecule comprises amino-oxy-acetyl. ### Claim 6 (depends on 1) The composition of claim 1, wherein said oxime linkage is selected from the group consisting of —CO—NH—CH2—CH═N—O—CH2, —NH—CO—CH═N—O—CH2—, and —C6H4—CH═N—O—CH2—. ### Claim 7 (depends on 1) The composition of claim 1, wherein said second organic molecule is selected from the group consisting of peptides, lipids, oligosaccharides, nucleic acids, and macromolecules formed by a combination thereof. ### Claim 8 (depends on 1) The composition of claim 1, wherein said polyoxime is immunogenic. ### Claim 9 (depends on 1) The composition of claim 1, wherein said second organic molecule comprises a polypeptide having a complementarity determining region of a native antibody. ### Claim 10 (depends on 1) The composition of claim 1, further comprising a third organic molecule linked to the baseplate and selected from the group consisting of metal chelating agents, detectable markers, lipophilic anchors, imaging agents, and therapeutic agents. ### Claim 11 (depends on 1) The composition of claim 1, wherein said second organic molecule comprises a member selected from the group consisting of metal chelating agents, detectable markers, lipophilic anchors, imaging agents, and therapeutic agents. ### Claim 12 (depends on 1) A pharmaceutical composition, comprising the polyoxime composition of claim 1 and a pharmaceutically acceptable carrier. ### Claim 13 (depends on 12) The pharmaceutical composition of claim 12, wherein said polyoxime composition is immunogenic and is present in an immunogenically effective amount. ### Claim 14 (depends on 13) A method of inducing an immune response in an animal, which comprises administering to said animal an immunologically effective amount of the composition of claim 13. ### Claim 15 (depends on 10, 11) A method of imaging a cell, comprising selecting a polyoxime composition of claim 10 or 11 comprising an imaging agent and contacting the cell with a detectable amount of the polyoxime composition. ### Claim 16 A homogeneous polyoxime composition prepared by a process comprising the steps of: 1) obtaining a first organic baseplate molecule having present therein a plurality of at least three identical orthogonal reactive groups capable of oxime linkage formation, wherein said orthogonal reactive groups are amino-oxy groups, aldehyde groups or keto groups; 2) obtaining a plurality of second organic molecules, each molecule having present therein a complementary orthogonal reactive group capable of oxime linkage formation with said orthogonal reactive group on said baseplate molecule, wherein said complementary orthogonal reactive groups are amino-oxy groups, aldehyde groups or keto groups, as appropriate for complementarity, and wherein said second organic molecules are identical in structure; 3) contacting said baseplate molecule with an amount of said second organic molecules sufficient for essentially complete reaction between said second organic molecules and said plurality of orthogonal reactive groups on said baseplate molecule under conditions allowing oxime linkage formation, whereby oxime linkage formation occurs between the orthogonal reactive groups on said baseplate and the complementary orthogonal reactive groups on said second organic molecules; and 4) separating the polyoxime product from unreacted second organic molecules. ### Claim 17 A method of producing a homogeneous polyoxime composition, comprising the steps of: 1) obtaining a first organic baseplate molecule having present therein a plurality of at least three identical orthogonal reactive groups capable of oxime linkage formation, wherein said orthogonal reactive groups are amino-oxy groups, aldehyde groups or keto groups, and wherein said second organic molecules are identical in structure; 2) obtaining a plurality of second organic molecules each molecule having present therein a complementary orthogonal reactive group capable of oxime linkage formation with said orthogonal reactive group on said baseplate molecule, wherein said complementary orthogonal reactive groups are amino-oxy groups, aldehyde groups or keto groups, as appropriate for complementarity; 3) contacting said baseplate molecule with an amount of said second organic molecules sufficient for essentially complete reaction between said second organic molecules and said plurality of orthogonal reactive groups on said baseplate molecule under conditions allowing oxime linkage formation, whereby oxime linkage formation occurs between the orthogonal reactive groups on said baseplate and the complementary orthogonal reactive groups on said second organic molecules; and 4) separating the polyoxime product from unreacted second organic molecules. ### Claim 18 (depends on 17) The method of claim 17, wherein said contacting mixing occurs at a pH equal to or less than 5.