Abstract: An insulin conjugate is disclosed in which insulin is coupled to a modifying moiety of the formula X—R1—Y-PAG-Z—R2 wherein X, Y, and Z are linking groups, R2 is a capping group, and PAG is a carbon chain that incorporates one or more alkylene glycol moieties.

Abstract: An insulin compound coupled to a modifying moiety having a formula: —X—R1—Y-PAG-Z—R2??(Formula VI) where, X, Y and Z are independently selected linking groups and each is optionally present, and X, when present, is coupled to the insulin compound by a covalent bond, either R1 or R2 is a lower alkyl, optionally including a carbonyl group, and when R1 is a lower alkyl, R2 is a capping group, and PAG is a linear or branched carbon chain incorporating one or more alkalene glycol moieties, and optionally incorporating one or more additional moieties selected from the group consisting of —S—, —O—, —N—, and —C(O)—.

Abstract: Methods are disclosed for preparing compounds of Formula I: where R1, R3, and R4 are independently hydrogen or C1 to C4 alkyl, and R2 is: where R5 is selected from the group consisting of hydrogen and C1 to C4 alkyl, or where R6, R7 and R8 are independently hydrogen or C1 to C4 alkyl; or the esters or pharmacologically acceptable salts thereof. The compounds and or their metabolites can be used to treat or prevent various diseases, particularly inflammatory conditions of the GI tract.

Abstract: Fatty acid compositions for administration of of pharmaceutical agents, such as proteins and peptides, protein and peptide conjugates, and/or cation-polypeptide conjugate complexes. In particular, the invention provides a solid pharmaceutical composition formulated for oral administration by ingestion, having from about 0.1 to about 75% w/w fatty acid component, where the fatty acid component comprises saturated or unsaturated C4, C5, C6, C7, C8, C9, C10, C11, or C12 fatty acids and/or salts of such fatty acids; and a therapeutic agent. Further, the invention provides a liquid pharmaceutical composition formulated for oral administration by ingestion, comprising: from about 0.1 to about 10% w/v fatty acid component, where the fatty acid component comprises saturated or unsaturated C4, C5, C6, C7, C8, C9, C10, C11, or C12 fatty acids and/or salts of such fatty acids; and a therapeutic agent.

Abstract: Methods are disclosed for preparing compounds of Formula I: where R1, R3, and R4 are independently hydrogen or C1 to C4 alkyl, and R2 is: where R5 is selected from the group consisting of hydrogen and C1 to C4 alkyl, or where R6, R7 and R8 are independently hydrogen or C1 to C4 alkyl; or the esters or pharmacologically acceptable salts thereof. The compounds and or their metabolites can be used to treat or prevent various diseases, particularly inflammatory conditions of the GI tract.

Abstract: A simple chain-extending approach was established for the scale-up of the monoprotected monodisperse PEG diol materials. Reactions of THP-(OCH2CH2)n—OMs (n=4, 8, 12) with a large excess of commercially available H—(OCH2CH2)n—OH (n=1-4) under basic conditions led to THP-(OCH2CH2)n—OH (n=5-15). Similarly, Me-(OCH2CH2)n—OH (n=4-11, 13) were prepared from Me-(OCH2CH2)n—OMs (n=3, 7, 11). For the chain elongation steps, 40-80% yields were achieved through extraction purification. PEG oligomer libraries I and II were generated in 50-95% overall yields by alkylation or acylation of THP-(OCH2CH2)n—OH (n=1-15) followed by deprotection. Alkylation of Me-(OCH2CH2)n—OH (n=1-11, 13) with X—(CH2)m—CO2R (X=Br or OMs) and subsequent hydrolysis led to PEG oligomer library III in 30-60% overall yields. Combinatorial purification techniques were adapted to the larger-scale library synthesis. A total of 498 compounds, each with a weight of 2-5 g and a minimum purity of 90%, were synthesized.

Abstract: Methods are disclosed for preparing compounds of Formula I: where R1, R3, and R4 are independently hydrogen or C1 to C4 alkyl, and R2 is: where R5 is selected from the group consisting of hydrogen and C1 to C4 alkyl, or where R6, R7 and R8 are independently hydrogen or C1 to C4 alkyl; or the esters or pharmacologically acceptable salts thereof. The methods can involve converting a suitably functionalized aniline compound to a diazonium salt (which aniline compound can be first formed by reduction of a nitrobenzene) and coupling the diazonium salt with a suitably functionalized benzene compound. The suitably functionalized aniline compound either includes a primary alcohol or aldehyde group, which is then oxidized to a carboxylic acid group, or includes a nitrile or amide group, which is hydrolyzed to a carboxylic acid group. The methods can also involve the direct coupling (via reduction of nitro groups to form an azo linkage) of suitably functionalized nitrobenzenes.

Abstract: The present invention provides a compound having a formula: where R1 is selected from the group consisting of alkyl, CH2(OC2H4)OCH3, and —(OC2H4)OCH3; n is 0-4; Olig is an oligomer having a formula: -L-O-PAGR.R2]q where L is a optional linker moiety selected from the group consisting of —CH2O—, —CH2OX—, —OX—, —C(O)—, —C(O)X, —NH—, —NHC(O)—, —XNHC(O)—, —NHC(O)X—, —C(O)NH—, —C(O)NHX—, and where X is alkyl1-6 or is not present, Y is N or O or is not present, and R3 is alkyl1-6; PAG is a linear or branched polyalkylene glycol moiety; R2 is an alkyl1-22 capping moiety if X is present or alkyl2-22 if X is not present; and q is a number from 1 to the maximum number of branches on PAG; and m is 1-5.

Abstract: The invention provides compositions comprising 4-APAA compounds and methods for treating disorders involving inflammation of the intestinal system, such as inflammatory bowel disease. The methods and compositions of the invention also include combinations of 4-APAA compounds and 5-ASA compounds for treatment of such disorders.

Abstract: Calcitonin drug-oligomer conjugates that include a calcitonin drug coupled to an oligomer including a single polyalkylene glycol moiety consisting of between 4 and 10 polyalkylene glycol subunits are disclosed. Pharmaceutical compositions including such conjugates and methods of treating bone disorders by administering such conjugates are also disclosed.

Abstract: Methods are disclosed for preparing compounds of Formula I: where R1, R3, and R4 are independently hydrogen or C1 to C4 alkyl, and R2 is: where R5 is selected from the group consisting of hydrogen and C1 to C4 alkyl, or where R6, R7 and R8 are independently hydrogen or C1 to C4 alkyl; or the esters or pharmacologically acceptable salts thereof. The methods can involve converting a suitably functionalized aniline compound to a diazonium salt (which aniline compound can be first formed by reduction of a nitrobenzene) and coupling the diazonium salt with a suitably functionalized benzene compound. The suitably functionalized aniline compound either includes a primary alcohol or aldehyde group, which is then oxidized to a carboxylic acid group, or includes a nitrile or amide group, which is hydrolyzed to a carboxylic acid group. The methods can also involve the direct coupling (via reduction of nitro groups to form an azo linkage) of suitably functionalized nitrobenzenes.

Abstract: An insulin compound coupled to a modifying moiety having a formula: —X—R1—Y—PAG-Z—R2??(Formula VI) where, X, Y and Z are independently selected linking groups and each is optionally present, and X, when present, is coupled to the insulin compound by a covalent bond, either R1 or R2 is a lower alkyl, optionally including a carbonyl group, and when R1 is a lower alkyl, R2 is a capping group, and PAG is a linear or branched carbon chain incorporating one or more alkalene glycol moieties, and optionally incorporating one or more additional moieties selected from the group consisting of —S—, —O—, —N—, and —C(O)—.

Abstract: An insulin compound coupled to a modifying moiety having a formula: —X—R1—Y-PAG-Z—R2 ??(Formula VI) where, X, Y and Z are independently selected linking groups and each is optionally present, and X, when present, is coupled to the insulin compound by a covalent bond, either R1 or R2 is is a lower alkyl, optionally including a carbonyl group, and when R1 is a lower alkyl, R2 is a capping group, and PAG is a linear or branched carbon chain incorporating one or more alkalene glycol moieties, and optionally incorporating one or more additional moieties selected from the group consisting of —S—, —O—, —N—, and —C(O)—.

Abstract: Methods are disclosed for preparing compounds of Formula I: where R1, R3, and R4 are independently hydrogen or C1 to C4 alkyl, and R2 is: where R5 is selected from the group consisting of hydrogen and C1 to C4 alkyl, or where R6, R7 and R8 are independently hydrogen or C1 to C4 alkyl; or the esters or pharmacologically acceptable salts thereof. The methods can involve converting a suitably functionalized aniline compound to a diazonium salt (which aniline compound can be first formed by reduction of a nitrobenzene) and coupling the diazonium salt with a suitably functionalized benzene compound. The suitably functionalized aniline compound either includes a primary alcohol or aldehyde group, which is then oxidized to a carboxylic acid group, or includes a nitrile or amide group, which is hydrolyzed to a carboxylic acid group. The methods can also involve the direct coupling (via reduction of nitro groups to form an azo linkage) of suitably functionalized nitrobenzenes.

Abstract: The invention provides a complex including a cation and an insulin compound conjugate. The insulin compound conjugate includes insulin compound, such as human insulin or an analog thereof, conjugated to a modifying moiety, such as a polyethylene glycol moiety. The invention also includes solids and pharmaceutical compositions including such complexes, methods of making such complexes, and methods of using such complexes in the treatment of insulin compound deficiencies and other ailments. Further, the invention includes novel insulin compound conjugates and modifying moieties for use in making novel insulin compound conjugates. The invention also includes fatty acid compositions for administration of pharmaceutical agents, such as the novel insulin compound conjugates, and/or the cation-insulin compound conjugate complexes of the invention.

Abstract: An insulin compound coupled to a modifying moiety having a formula: —X—R1—Y-PAG-Z—R??(Formula VI) where, X, Y and Z are independently selected linking groups and each is optionally present, and X, when present, is coupled to the insulin compound by a covalent bond, either R1 or R2 is is a lower alkyl, optionally including a carbonyl group, and when R1 is a lower alkyl, R2 is a capping group, and PAG is a linear or branched carbon chain incorporating one or more alkalene glycol moieties, and optionally incorporating one or more additional moieties selected from the group consisting of —S—, —O—, —N—, and —C(O)—, and where the modifying moiety has a maximum number of 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 heavy atoms.

Abstract: Modified natriuretic compounds and conjugates thereof are disclosed in the present invention. In particular, conjugated forms of hBNP are provided that include at least one modifying moiety attached thereto. The modified natriuretic compound conjugates retain activity for stimulating cGMP production, binding to NPR-A receptor, and in some embodiments an improved half-life in circulation as compared to unmodified counterpart natriuretic compounds. Oral, parenteral, enteral, subcutaneous, pulmonary, and intravenous forms of the compounds and conjugates may be prepared as treatments and/or therapies for heart conditions particularly congestive heart failure. Modifying moieties comprising oligomeric structures having a variety of lengths and configurations are also disclosed. Analogs of the natriuretic compound are also disclosed, having an amino acid sequence that is other than the native sequence.

Abstract: Calcitonin drug-oligomer conjugates that include a calcitonin drug coupled to an oligomer including a single polyalkylene glycol moiety consisting of between 4 and 10 polyalkylene glycol subunits are disclosed. Pharmaceutical compositions including such conjugates and methods of treating bone disorders by administering such conjugates are also disclosed.

Abstract: Fatty acid compositions for administration of of pharmaceutical agents, such as proteins and peptides, protein and peptide conjugates, and/or cation-polypeptide conjugate complexes. In particular, the invention provides a solid pharmaceutical composition formulated for oral administration by ingestion, having from about 0.1 to about 75% w/w fatty acid component, where the fatty acid component comprises saturated or unsaturated C4, C5, C6, C7, C8, C9, C10, C11, or C12 fatty acids and/or salts of such fatty acids; and a therapeutic agent. Further, the invention provides a liquid pharmaceutical composition formulated for oral administration by ingestion, comprising: from about 0.1 to about 10% w/v fatty acid component, where the fatty acid component comprises saturated or unsaturated C4, C5, C6, C7, C8, C9, C10, C11, or C12 fatty acids and/or salts of such fatty acids; and a therapeutic agent.

Abstract: Calcitonin drug-oligomer conjugates that include a calcitonin drug coupled to an oligomer including a single polyalkylene glycol moiety consisting of between 4 and 10 polyalkylene glycol subunits are disclosed. Pharmaceutical compositions including such conjugates and methods of treating bone disorders by administering such conjugates are also disclosed.