HUMAN CYTOMEGALOVIRUS GB POLYPEPTIDE

The present invention relates to polypeptides and cytomegalovirus (CMV) antigens that include at least one introduced amino acid mutation relative to the amino acid sequence of the wild-type HCMV glycoprotein B (gB). In some embodiments, the polypeptide is stabilized in a conformation alternative to the gB postfusion conformation. Also disclosed are compositions including the polypeptides and uses thereof. 1. A polypeptide comprising an amino acid sequence set forth in any one of SEQ ID NOs:1-106.2. The polypeptide according to claim 1 , wherein the sequence comprises SEQ ID NO: 56.3. The polypeptide according to claim 1 , wherein the sequence comprises SEQ ID NO: 57.4. The polypeptide according to claim 1 , wherein the sequence comprises SEQ ID NO: 58.5. The polypeptide according to claim 1 , wherein the sequence comprises SEQ ID NO: 75.6. A polynucleotide encoding a polypeptide comprising an amino acid sequence set forth in any one of SEQ ID NOs: 1-106.7. A composition comprising a polypeptide comprising the sequence set forth in any one of SEQ ID NOs:1-106; and a diluent.8. The composition according to claim 7 , wherein the sequence does not comprise any one of SEQ ID NO: 59 claim 7 , SEQ ID NO: 75 claim 7 , SEQ ID NO: 76 claim 7 , SEQ ID NO: 71 claim 7 , SEQ ID NO: 52 claim 7 , SEQ ID NO: 96 claim 7 , and SEQ ID NO: 50.9. The composition according to claim 7 , further comprising a polypeptide comprising any one sequence selected from SEQ ID NOS: 211-224.10. A composition comprising a polynucleotide encoding a polypeptide comprising the sequence selected from any one of SEQ ID NOs:1-106; and a diluent.11. The composition according to claim 10 , further comprising a polynucleotide comprising a sequence selected from any one of SEQ ID NOS: 141-210.12. The composition according to claim 10 , further comprising a polynucleotide comprising a sequence selected from any one of SEQ ID NOS: 224-254.13. A method of eliciting an immune response in a mammal claim 10 , ...

Fluoro-pyridinone phosphates and boronates useful as antibacterial agents

The present invention is directed to a new fluoro-pyridinone hydroxamic acid phosphates and boronates of Formulae I, II and III wherein Q is selected from the group consisting of —P(O)(OH) 2 , —P(O)(OH)(O − M + ), —P(O)(O − M + ) 2 and —P(O)(O − ) 2 M 2+ ; M + at each occurrence is a pharmaceutically acceptable monovalent cation; and M 2+ is a pharmaceutically acceptable divalent cation and their use as LpxC inhibitors and, more specifically, their use to treat bacterial infections.

RSV F protein mutants

The present disclosure relates to RSV F protein mutants, nucleic acids or vectors encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and compositions.

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylam ides and analogues thereof, having the structure:or a pharmaceutically acceptable salt thereof, as set forth in the Description. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

PYRROLO[2,3-D]PYRIMIDINYL, PYRROLO[2,3-B]PYRAZINYL AND PYRROLO[2,3-D]PYRIDINYL ACRYLAMIDES

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK. 123-. (canceled)25. The method of claim 24 , wherein the compound is selected from the group consisting of:2-(1-acryloylpiperidin-4-ylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;N-isopropyl-2-(3-(N-methylacrylamido)azetidin-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;2-((3R,4R)-1-acryloyl-3-hydroxypiperidin-4-ylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;(S)-2-(1-acryloylpyrrolidin-3-ylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;(S)-2-((1-acryloylpyrrolidin-2-yl)methylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;2-((1R,3R)-3-acrylamidocyclobutylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;(S)-2-((1-acryloylpyrrolidin-3-yl)methylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;(R)-4-(1-acryloylpiperidin-3-ylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;(R)-1-(3-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)prop-2-en-1-one;1-((2S,5R)-5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-2-methylpiperidin-1-yl)prop-2-en-1-one;1-((3R,5S)-3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-5-hydroxypiperidin-1-yl)prop-2-en-1-one;(R)-1-(3-(5-(2-methoxyethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)prop-2-en-1-one;1-(5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-2-(hydroxymethyl)piperidin-1-yl)prop-2-en-1-one;1-((3R,5S)-3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-5-fluoropiperidin-1-yl)prop-2-en-1-one;1-((3R,4S)-3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-4-methylpiperidin-1-yl)prop-2-en-1-one;1-((3S,4R)-3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-4-fluoropiperidin-1-yl)prop-2-en-1-one;1-((2S,5R)-5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)- ...

RSV F Protein Mutants

The present disclosure relates to RSV F protein mutants, nucleic acids or vectors encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and compositions. 1. A mutant of a wild-type RSV F protein , which mutant comprises a F1 polypeptide and a F2 polypeptide , wherein the mutant comprises at least one amino acid mutation relative to the amino acid sequence of the wild-type RSV F protein , and wherein the amino acid mutation is selected from the group consisting of:(1) an engineered disulfide bond mutation;(2) a cavity filling mutation;(3) an electrostatic mutation;(4) a combination of at least one engineered disulfide mutation and at least one cavity filling mutation;(5) a combination of at least one engineered disulfide mutation and at least one electrostatic mutation;(6) a combination of at least one cavity filling mutation and at least one electrostatic mutation; and(7) a combination of at least one engineered disulfide mutation, at least one cavity filling mutation, and at least one electrostatic mutation.2. The mutant according to claim 1 , wherein the amino acid mutation is a combination of at least one engineered disulfide mutation claim 1 , at least one cavity filling mutation claim 1 , and at least one electrostatic mutation.3. The mutant according to claim 1 , which is in the form of a trimer.4. The mutant according to claim 1 , which has increased stability as compared with the corresponding wild-type RSV F protein claim 1 , wherein the stability is measured by binding of the mutant with antibody AM14.5. The mutant according to claim 1 , wherein the wild-type RSV is subtype A claim 1 , subtype B claim 1 , strain A2 claim 1 , strain Ontario claim 1 , or strain Buenos Aires.6. The mutant according to claim 2 , wherein the engineered disulfide mutation is selected from the group consisting of: 55C and 188C; 155C and 290C; 103C and 148C; and 142C and ...

Pyrrolo[2,3-D]pyrimidinyl, pyrrolo[2,3-B]pyrazinyl, pyrrolo[2,3-B]pyridinyl acrylamides and epoxides thereof

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl, and pyrrolo[2,3-b]pyridinyl acrylamides, epoxides, and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

N-Link Hydroxamic Acid Derivatives Useful As Antibacterial Agents

The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors, and more specifically their use to treat bacterial infections. 2. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof in which Rand Rare each methyl.3. A compound according to claim 2 , or a pharmaceutically acceptable salt thereof in which Ris hydrogen.4. A compound according to claim 2 , or a pharmaceutically acceptable salt thereof in which said compound is the R-enantiomer.5. A compound according to claim 2 , or a pharmaceutically acceptable salt thereof in which L is absent.6. A compound according to claim 2 , or a pharmaceutically acceptable salt thereof in which G and T is absent.7. A compound according to claim 2 , or a pharmaceutically acceptable salt thereof in which D is (C-C)aryl optionally substituted.8. A compound according to claim 6 , or a pharmaceutically acceptable salt thereof in which D is optionally substituted phenyl.913.-. (canceled)14. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof in admixture with at least one pharmaceutically acceptable excipient.15. A method for treating bacterial infections comprising administering a compound according to claim 1 , or a pharmaceutically acceptable salt thereof to a patient in need thereof.16. (canceled) This invention relates to novel hydroxamic acid derivatives that are useful for the treatment of bacterial infections, especially Gram-negative infections. The invention also relates to methods of using such compounds in the treatment of bacterial infections in mammals, and to pharmaceutical compositions containing such compounds.Infection by Gram-negative bacteria such as , Extended Spectrum β-lactamase producing (ESBL) Enterobacteriaceae, and is a major health problem, especially in the case of hospital-acquired infections. In addition, there is an increasing level of resistance to current ...

N-link hydroxamic acid derivatives useful as antibacterial agents

The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors, and more specifically their use to treat bacterial infections.

RSV F Protein Mutants

The present disclosure relates to RSV F protein mutants, nucleic acids or vectors encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and compositions. 1. A mutant of a wild-type RSV F protein , which mutant comprises a F1 polypeptide and a F2 polypeptide , wherein the mutant comprises at least one amino acid mutation relative to the amino acid sequence of the wild-type RSV F protein , and wherein the amino acid mutation is selected from the group consisting of:(1) an engineered disulfide bond mutation;(2) a cavity filling mutation;(3) an electrostatic mutation;(4) a combination of at least one engineered disulfide mutation and at least one cavity filling mutation;(5) a combination of at least one engineered disulfide mutation and at least one electrostatic mutation;(6) a combination of at least one cavity filling mutation and at least one electrostatic mutation; and(7) a combination of at least one engineered disulfide mutation, at least one cavity filling mutation, and at least one electrostatic mutation.2. The mutant according to claim 1 , wherein the amino acid mutation is a combination of at least one engineered disulfide mutation claim 1 , at least one cavity filling mutation claim 1 , and at least one electrostatic mutation.3. The mutant according to claim 1 , which is in the form of a trimer.4. The mutant according to claim 1 , which has increased stability as compared with the corresponding wild-type RSV F protein claim 1 , wherein the stability is measured by binding of the mutant with antibody AM14.5. The mutant according to claim 1 , wherein the wild-type RSV is subtype A claim 1 , subtype B claim 1 , strain A2 claim 1 , strain Ontario claim 1 , or strain Buenos Aires.6. The mutant according to claim 2 , wherein the engineered disulfide mutation is selected from the group consisting of: 55C and 188C; 155C and 290C; 103C and 148C; and 142C and ...

RSV F Protein Mutants

The present disclosure relates to RSV F protein mutants, nucleic acids or vectors encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and compositions.

Fluoro-Pyridinone Phosphates And Boronates Useful As Antibacterial Agents

The present invention is directed to a new fluoro-pyridinone hydroxamic acid phosphates and boronates of Formulae I, II and III 3. The compound according to wherein Q is —P(O)(OH).4. The compound according to wherein Q is —P(O)(OH)(OM) claim 2 ,{'sup': −', '+, 'sub': '2', 'or —P(O)(OM).'}5. The compound according to wherein Q is —P(O)(OM).6. The compound according to wherein Q is —P(O)(O)M.7. The compound according to wherein M at each occurrence is independently selected from the group consisting of Li claim 4 , K and Na.8. The compound according to wherein M at each occurrence is a pharmaceutically acceptable monovalent cation independently selected from ammonium claim 4 , (C-Calkyl)ammonium claim 4 , (C-Calkyl)ammonium claim 4 , (C-Calkyl)ammonium claim 4 , (C-Calkyl)ammonium claim 4 , (C-Ccycloalkyl)ammonium claim 4 , (C-Ccycloalkyl)ammonium claim 4 , (C-Ccycloalkyl)ammonium claim 4 , (C-Ccycloalkyl)ammonium claim 4 , pyrrolidinium claim 4 , piperidinium and pyridinium; wherein each of the (C-Calkyl) or (C-Ccycloalkyl) moieties are optionally substituted with one to three hydroxy or halo.9. The compound according to wherein M at each occurrence is a pharmaceutically acceptable monovalent cation independently selected from the group consisting of glycinium claim 4 , alaninium claim 4 , β-alaninium claim 4 , valinium claim 4 , lysinium claim 4 , isoleucinium claim 4 , leucinium claim 4 , methioninium claim 4 , threoninium claim 4 , asparaginium claim 4 , glutaminium claim 4 , histidinium claim 4 , argininium claim 4 , ornithinium claim 4 , tryptophanium claim 4 , prolinium claim 4 , glutaminium claim 4 , cysteinium claim 4 , phenylalaninium claim 4 , tyrosinium and serinium.16. The compound according to wherein M is selected from the group consisting of Ca claim 6 , Mg and Zn.19. The compound according to wherein M is selected from the group consisting of Li claim 18 , K and Na.20. The compound according to wherein M is selected from ammonium claim 18 , (C-Calkyl) ...

N-link hydroxamic acid derivatives useful as antibacterial agents

The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors, and more specifically their use to treat bacterial infections.

FLUORO-PYRIDINONE DERIVATIVES USEFUL AS ANTIBACTERIAL AGENTS

The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors and, more specifically, their use to treat bacterial infections. 2. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof in which Rand Rare each methyl.3. A compound according to claim 2 , or a pharmaceutically acceptable salt thereof in which Ris hydrogen.4. A compound according to claim 3 , or a pharmaceutically acceptable salt thereof in which said compound is the R-enantiomer claim 3 , substantially pure.5. A compound according to claim 4 , or a pharmaceutically acceptable salt thereof in which T is represented by phenyl which may be optionally substituted.6. A compound according to claim 4 , or a pharmaceutically acceptable salt thereof in which D and E are both absent.7. A compound according to claim 4 , or a pharmaceutically acceptable salt thereof in which D is a bond.8. A compound according to claim 7 , or a pharmaceutically acceptable salt thereof in which E is represented by cyclohexyl claim 7 , pyrimidinyl claim 7 , triazolyl claim 7 , pyridinyl claim 7 , isoxazolyl claim 7 , or cyclopropyl claim 7 , any of which may be optionally substituted.911-. (canceled)12. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof in admixture with at least one pharmaceutically acceptable excipient.1314-. (canceled)15. A compound selected from the group consisting of(2R)-4-{5-fluoro-2-oxo-4-[4-(2H-tetrazol-2-yl)phenyl]pyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[5-fluoro-4-(2-fluoro-3-methylphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(4-chlorophenyl)-5-fluoro-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[5-fluoro-4-(2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-[4-(2,3-dihydro-1-benzofuran-5-yl)-5-fluoro-2-oxopyridin-1 ...

HUMAN CYTOMEGALOVIRUS GB POLYPEPTIDE

The present invention relates to polypeptides and cytomegalovirus (CMV) antigens that include at least two introduced amino acid mutations relative to the amino acid sequence of the wild-type HCMV glycoprotein B (gB). In some embodiments, the polypeptide is stabilized in a conformation alternative to the gB postfusion conformation. Also disclosed are compositions including the polypeptides and uses thereof. 1. A mutant of a wild-type cytomegalovirus (CMV) glycoprotein B (gB) protein , which mutant comprises at least two amino acid mutations relative to the amino acid sequence of the wild-type CMV gB protein , and wherein the amino acid mutation is selected from the group consisting of:(1) an engineered disulfide bond mutation;(2) an additional mutation; and(3) a combination of at least one engineered disulfide mutation and at least one additional mutation.2. The mutant according to claim 1 , wherein the amino acid mutations comprise a combination of at least two engineered disulfide mutations and at least one additional mutation.3. The mutant according to claim 1 , which is in the form of a trimer.4. The mutant according to claim 1 , which has increased stability in prefusion form as compared with the corresponding wild-type CMV gB protein claim 1 , wherein the stability is measured by binding of a prefusion-specific antibody claim 1 , thermal shift assay or EM imaging.5. The mutant according to claim 1 , wherein the wild-type CMV gB is Towne strain.6. The mutant according to claim 1 , wherein the engineered disulfide mutation is selected from the group consisting of: D217C and Y589C; M371C and W506C; and N524C and M684C.7. The mutant according to claim 1 , wherein the additional mutation is selected from the group consisting of:(1) substitution of YIH at positions 155-157 with GHR,(2) substitution of W at position 240 with A;(3) substitution of C at position 246 with S;(4) substitution of P at position 655 with S;(5) substitution of F at position 678 with S; and(6) ...

Cyclic Peptides As C5a Receptor Antagonists

The invention relates to cyclic peptide derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to cyclic peptide C5a receptor antagonists of formula (Ia) or formula (Ib), or pharmaceutically acceptable salts thereof, wherein R, R, R, Rand Rareas defined in the description. C5a receptor antagonists are potentially useful in the treatment of a wide range of 1 disorders, including inflammatory disorders and immune disorders. 2. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris OH claim 1 , O(CH)—C(O)OR claim 1 , NH claim 1 , NH—C(O)Ror NH(CH)—C(O)OR; or Ris NH claim 1 , NH—C(O)Ror NH(CH)—C(O)OR.3. A compound according to of formula (Ia) claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris OH or O(CH)—C(O)OR.4. A compound according to of formula (Ia) claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris OH.5. A compound according to of formula (Ib) claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris NH claim 1 , NH—C(O)Ror NH(CH)—C(O)OR.6. A compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris a 9-membered heteroaryl containing one or two nitrogen atoms and wherein the heteroaryl is optionally substituted on a ring carbon atom with one or two R.9. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris methyl or methoxy.10. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H.11. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , selected from:N-[(2S)-1-{[(3R,6S,9S,15S,19R,20aS)-9-(3-carbamimidamidopropyl)-19-hydroxy-3-[(cis-4-hydroxycyclohexyl)methyl]-6-(1H-indol-3-ylmethyl)-1,4,7,10,16-pentaoxoicosahydropyrrolo[1,2-a][1,4,7,10,13] ...

E. COLI FIMH MUTANTS AND USES THEREOF

This disclosure relates to the design of E. coli mutated FimH polypeptides that result in improved biochemical properties and immunogenicity, compositions comprising such polypeptides, and uses thereof.

PYRIDINONE AND PYRIMIDINONE PHOSPHATES AND BORONATES USEFUL AS ANTIBACTERIAL AGENTS

The present invention is directed to new pyridinone or pyrimidinone hydroxamic acid phosphates of Formula (1) and boronates of Formula (2), stereoisomers thereof; 4. The Formula (1a) compound of wherein Q is —P(O)(OH);{'sup': −', '+', '−', '+', '−', '2+', '+', '+', '+', '+', '+', '+', '+', '+', '2+', '2+', '2+', '2+, 'sub': 2', '2', '4', '3', '2', '3', '2', '2', '3', '2', '2', '2', '3', '2, '—P(O)(OH)(OM); —P(O)(OM); or —P(O)(O)M; M at each occurrence is independently selected from the group consisting of Li, K, and Na, or M+ at each occurrence is a pharmaceutically acceptable monovalent cation independently selected from NH, NHC(CHOH), NH(CHCH); NH(CHCH); pyrrolidinium; and glycinium; and wherein M is selected from the group consisting of Ca, Mg and Zn.'}7. The compound of claim 6 , wherein M is selected from the group consisting of Li claim 6 , K claim 6 , and Na claim 6 , NH claim 6 , NHC(CHOH) claim 6 , NH(CHCH) claim 6 , NH(CHCH) claim 6 , pyrrolidinium claim 6 , and glycinium.8. A pharmaceutical composition comprising a compound of of in admixture with at least one pharmaceutically acceptable excipient claim 1 , diluent or carrier.9. A method for treating a bacterial infection in a patient claim 1 , in need thereof claim 1 , the method comprising administering a therapeutically effective amount of a compound of to a patient claim 1 , wherein the therapeutically effective amount of the compound is administered orally claim 1 , topically claim 1 , or by injection.10. The method of wherein the bacterial infection is a Gram-negative bacterial infection.11Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Actinobacillus pleuropneumoniae, Salmonella enteritidis, Salmonella gallinarium, Lawsonia intracellularis, Brachyspira hyodysenteriae, Brachyspira pilosicoli, Acinetobacter baumannii, AcinetobacterCitrobacterEnterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Serratia marcescens, ...

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof, having the structure: or a pharmaceutically acceptable salt or solvate thereof, or an enantiomer or diastereomer thereof, as set forth in the Description. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

Fluoro-pyridinone derivatives useful as antibacterial agents

The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors and, more specifically, their use to treat bacterial infections.

RSV F Protein Mutants

The present disclosure relates to RSV F protein mutants, nucleic acids or vectors encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and compositions.

N-Link Hydroxamic Acid Derivatives Useful As Antibacterial Agents

The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors, and more specifically their use to treat bacterial infections. 116-. (canceled)17. A pharmaceutical composition comprising a therapeutically effective amount of a compound selected from the group consisting of(2R)—N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(2,3,4-trifluorophenyl)pyridin-1(2H)-yl]butanamide;(2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-1 (2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)-4-(4-(2-fluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide;(2R)—N-hydroxy-4-[4-{4-[(trans-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide;(2R)—N-hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}butanamide;or a pharmaceutically acceptable salt thereof; in admixture with at least one pharmaceutically acceptable excipient.18. The pharmaceutical composition of wherein the compound is (2R)—N-hydroxy-2-methyl-2-(methylsulfonyl)-4-[2-oxo-4-(2 claim 17 ,3 claim 17 ,4-trifluorophenyl)pyridin-1(2H)-yl]butanamide; or a pharmaceutically acceptable salt thereof.19. The pharmaceutical composition of wherein the compound is (2R)-4-[4-(4-chloro-2 claim 17 ,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide; or a pharmaceutically acceptable salt thereof.20. The pharmaceutical composition of wherein the compound is (2R)-4-(4-(2-fluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide; or a pharmaceutically acceptable salt thereof.21. The pharmaceutical composition of wherein the compound is (2R)—N-hydroxy-4-[4-{4-[(trans-4-hydroxycyclohexyl)methoxy]phenyl}-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanamide; or a pharmaceutically acceptable salt thereof.22. The pharmaceutical composition of wherein the compound is (2R)—N-hydroxy-2 ...

PYRROLO[2,3-D]PYRIMIDINYL, PYRROLO[2,3-B]PYRAZINYL AND PYR-ROLO[2,3-D]PYRIDINYL ACRYLAMIDES

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK. 11. The compound of selected from the group consisting of:2-(1-acryloylpiperidin-4-ylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;N-isopropyl-2-(3-(N-methylacrylamido)azetidin-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;2-((3R,4R)-1-acryloyl-3-hydroxypiperidin-4-ylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;(S)-2-(1-acryloylpyrrolidin-3-ylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;(S)-2-((1-acryloylpyrrolidin-2-yl)methylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;2-((1R,3R)-3-acrylamidocyclobutylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide; and,(S)-2-((1-acryloylpyrrolidin-3-yl)methylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide; or, a pharmaceutically acceptable salt thereof.12. The compound of selected from the group consisting of:(R)-4-(1-acryloylpiperidin-3-ylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;(R)-4-(1-acryloylpiperidin-3-ylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;(R)-1-(3-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)prop-2-en-1-one;1-((2S,5R)-5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-2-methylpiperidin-1-yl)prop-2-en-1-one;1-((3R,5S)-3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-5-hydroxypiperidin-1-yl)prop-2-en-1-one;(R)-1-(3-(5-(2-methoxyethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)prop-2-en-1-one;1-(5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-2-(hydroxymethyl)piperidin-1-yl)prop-2-en-1-one;1-((3R,5S)-3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-5-fluoropiperidin-1-yl)prop-2-en-1-one;1-((3R,4S)-3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-4-methylpiperidin-1-yl)prop-2-en-1-one;1 ...

RSV F protein mutants

The present disclosure relates to RSV F protein mutants, nucleic acids or vectors encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and compositions.

N-link hydroxamic acid derivatives useful as antibacterial agents

The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors, and more specifically their use to treat bacterial infections.

N-linked hydroxamic acid derivatives useful as antibacterial agents

The present invention is directed to a new class of hydroxamic acid derivatives of formula I, wherein the variables G, T, D, L, R1, R2, R3 are as described herein, their use as LpxC inhibitors, and more specifically their use to treat bacterial infections in a patient in need thereof.

N-Linked Hydroxamic Acid Derivatives Useful As Antibacterial Agents

The present invention is directed to a new class of hydroxamic acid derivatives of formula I, wherein the variables G, T, D, L, R1, R2, R3 are as described herein, their use as LpxC inhibitors, and more specifically their use to treat bacterial infections in a patient in need thereof.

FLUORO-PYRIDINONE DERIVATIVES USEFUL AS ANTIBACTERIAL AGENTS

The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors and, more specifically, their use to treat bacterial infections. 2. A compound according to in which Rand Rare each methyl.3. A compound according to or in which Ris hydrogen.4. A compound according to or in which said compound is the R-enantiomer claim 1 , substantially pure.5. A compound according to any of claim 1 , claim 1 , or in which T is represented by phenyl which may be optionally substituted.6. A compound according to any of claim 1 , claim 1 , claim 1 , or in which D and E are both absent.75. A compound according to any of - in which D is a bond.8. A compound according to in which E is represented by cyclohexyl claim 7 , pyrimidinyl claim 7 , triazolyl claim 7 , pyridinyl claim 7 , isoxazolyl claim 7 , or cyclopropyl claim 7 , any of which may be optionally substituted.10. (2R)-4-{5-Fluoro-2-oxo-4-[4-(2H-1 claim 7 ,2 claim 7 ,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide claim 7 , or a pharmaceutically acceptable salt thereof.11. (2R)-4-[5-Fluoro-4-(2-fluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide claim 7 , or a pharmaceutically acceptable salt thereof.1211. A pharmaceutical composition comprising a compound according to any of - in admixture with at least one pharmaceutically acceptable excipient.1311. A method for treating bacterial infections comprising administering a compound according to any of - to a patient in need thereof.1411. Use of a compound according to any of - in the manufacture of a medicament for bacterial infections. This invention relates to novel hydroxamic acid derivatives. The invention also relates to methods of using such compounds in the treatment of bacterial infections (especially Gram-negative infections) and to pharmaceutical compositions containing such compounds.Infection by Gram-negative bacteria such as , Extended Spectrum ...

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl, pyrrolo[2,3-b]pyridinyl acrylamides and epoxides thereof

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl, and pyrrolo[2,3-b]pyridinyl acrylamides, epoxides, and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

N-Link Hydroxamic Acid Derivatives Useful As Antibacterial Agents

The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors, and more specifically their use to treat bacterial infections.

HETEROARYL SULFONE-BASED CONJUGATION HANDLES, METHODS FOR THEIR PREPARATION, AND THEIR USE IN SYNTHESIZING ANTIBODY DRUG CONJUGATES

The present invention is directed to novel heteroaryl sulfone-based conjugation handles of the formula: (wherein R, R, Het, D, E, X, Y, Z, m, n, p, q, r, s and t are as defined herein), methods for their preparation, their use in synthesizing antibody drig conjugates, and the resulting antibody drig conjugates made with components having heteroaryl sulfone-based conjugation handles. 6. The compound of or , or a pharmaceutically acceptable salt or solvate thereof , wherein D is a cytotoxic moiety.7. The compound of claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein D is selected from the group consisting of: an anthracycline claim 6 , an auristatin claim 6 , a spliceostatin claim 6 , a CBI dimer claim 6 , a CPI dimer claim 6 , a CTI dimer claim 6 , dimers comprising two different monomers selected from CBI claim 6 , CPI and CTI claim 6 , an enediyne optionally selected from a calicheamicin claim 6 , an esperamycin and a neocarzinostatin claim 6 , a duocarmycin claim 6 , a geldanamycin claim 6 , a maytansine claim 6 , a puromycin claim 6 , a taxane claim 6 , a vinca alkaloid claim 6 , SN 38 claim 6 , a tubulysin claim 6 , a hemiasterlin claim 6 , a camptothecin claim 6 , a combretastatin claim 6 , a dolastatin claim 6 , an indolino benzodiazepine dimer claim 6 , a pyrrolobenzodiazepine dimer and a pladienolide claim 6 , and stereoisomers claim 6 , isosteres claim 6 , analogs claim 6 , or derivatives thereof; orD is a therapeutic agent, an anti-viral agent, an immunological agent, a fluorophore, a non-fluorophore imaging agent.8. The compound of claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein D is selected from: dolestatin claim 6 , MMAD claim 6 , MMAE claim 6 , MMAF claim 6 , PF-06380101 claim 6 , PF-06463377 claim 6 , PF-06456780 claim 6 , PF-06843982 claim 6 , PF-06874082 claim 6 , PF-06852321 claim 6 , PF-06757725 claim 6 , PF-06859944 and PF-06698970.9. The compound of or or a pharmaceutically ...

Heteroaryl sulfone-based conjugation handles, methods for their preparation, and their use in synthesizing antibody drug conjugates

The present invention is directed to novel heteroaryl sulfone-based conjugation handles of the formula: (wherein R 1 , R 2 , Het, D, E, X, Y, Z, m, n, p, q, r, s and t are as defined herein), methods for their preparation, their use in synthesizing antibody drig conjugates, and the resulting antibody drig conjugates made with components having heteroaryl sulfone- based conjugation handles.

Heteroaryl sulfone-based conjugation handles, methods for their preparation, and their use in synthesizing antibody drug conjugates

The present invention is directed to novel heteroaryl sulfone-based conjugation handles of the formula: (wherein R 1 , R 2 , Het, D, E, X, Y, Z, m, n, p, q, r, s and t are as defined herein), methods for their preparation, their use in synthesizing antibody drig conjugates, and the resulting antibody drig conjugates made with components having heteroaryl sulfone- based conjugation handles.

E. coli fimh mutants and uses thereof

This disclosure relates to the design of E. coli mutated FimH polypeptides that result in improved biochemical properties and immunogenicity, compositions comprising such polypeptides, and uses thereof.

PYRROLO[2,3-D]PYRIMIDINYL, PYRROLO[2,3-B]PYRAZINYL AND PYRROLO[2,3-D]PYRIDINYL ACRYLAMIDES

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

RSV F protein mutants

The present disclosure relates to RSV F protein mutants, nucleic acids or vectors encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and compositions.

Fluoro-pyridinone derivatives useful as antibacterial agents

The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors and, more specifically, their use to treat bacterial infections.

Rsv f protein mutants

【課題】対応する野生型ＲＳＶ Ｆタンパク質のアミノ酸配列に対する、アミノ酸配列において導入された突然変異を呈し、かつ野生型ＲＳＶ Ｆタンパク質に対してまたは野生型Ｆタンパク質を含むウイルスに対して免疫原性である野生型ＲＳＶ Ｆタンパク質の突然変異体を提供する。【解決手段】Ｆ１ポリペプチドおよびＦ２ポリペプチドを含み、野生型ＲＳＶ Ｆタンパク質のアミノ酸配列に対する少なくとも１つのアミノ酸突然変異を含む、野生型ＲＳＶ Ｆタンパク質の突然変異体であって、アミノ酸突然変異が（ｉ）１５５Ｃおよび２９０Ｃのシステイン突然変異の対、ならびに（ｉｉ）１）１９０位のＩによるアミノ酸置換、２）５４位のＩ、Ｙ、Ｌ、Ｈ、またはＭによるアミノ酸置換、および３）２９６位のＩ、Ｙ、またはＨによるアミノ酸置換からなる群から選択される１つまたは複数の間隙充填突然変異を含む、突然変異体である。【選択図】なし

N-linked hydroxamic acid derivatives useful as antibacterial agents

The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors, and more specifically their use to treat bacterial infections. Formula (I).

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides

N-linked hydroxamic acid derivatives useful as antibacterial agents

【課題】新しいＬｐｘＣ阻害剤、より具体的には、細菌感染症を治療するためのそれらの使用方法及びその様な化合物を含有する医薬組成物の提供。【解決手段】式（Ｉ）で表されるヒドロキサム酸誘導体又は薬学的に許容できるその塩。（Ｒ１はＣ１〜３のアルキル；Ｒ２はＨ又はＣ１〜３のアルキル；Ｒ３はＨ、ハロゲン、Ｃ１〜３のアルキル、トリフルオロメチル等；Ｌは存在しないか、アルキレン、アルケニレン等；Ｄはシクロアルキル、アリール等；Ｔは（ＣＨ２）ｑ、Ｓ−（ＣＨ２）ｚ−Ｏ−（ＣＨ２）ｎ等；Ｇは存在しないか、シクロアルキル等）【選択図】なし

N-linked hydroxamic acid derivatives useful as antibacterial agents

The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors, and more specifically their use to treat bacterial infections. Formula (I).

RSV F protein mutants

RSV F PROTEIN MUTANTS The present disclosure relates to RSV F protein mutants, nucleic acids or vectors 5 encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and compositions.

Rsv f protein mutants.

La presente descripción se relaciona con mutantes, ácidos nucleicos o vectores de proteína F de RSV, que codifican un mutante de proteína F de RSV, composiciones o ácidos nucleicos que comprenden un mutante de proteína F de RSV, y usos de los mutantes, ácidos nucleicos o vectores de proteína F de RSV y composiciones.

RSV F protein mutants

RSV F PROTEIN MUTANTS ABSTRACT The present disclosure relates to RSV F protein mutants, nucleic acids or vectors 5 encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and compositions.

USEFUL FLUORO-PIRIDINONE DERIVATIVES AS ANTIBACTERIAL AGENTS

La presente invención se refiere a una nueva clase de derivados de ácido hidroxámico, su uso como inhibidores de LpxC y, más específicamente, a su uso para tratar infecciones bacterianas.

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

USEFUL FLUORO-PIRIDINONE DERIVATIVES AS ANTI-BACTERIAL AGENTS.

La presente invención se refiere a una nueva clase de derivados de ácido hidroxámico, su uso como inhibidores de LpxC y, más específicamente, a su uso para tratar infecciones bacterianas.

RSV F protein mutants

The present disclosure relates to RSV F protein mutants, nucleic acids or vectors encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and compositions.

? PIRROLO ACRYLAMIDS [2,3-D] PIRIMIDINI LO, PIRROLO [2,3-B] IRAZINYL AND PIRROLO [2,3-D] PIRIDINYL?

La presente invención provee acrilamidas farmacéuticamente activas de pirrolo[ 2,3-d]pirimidinilo y pirrolo [2,3-d]piridinilo y análogos de las mismas. Dichos compuestos son útiles para inhibir quinasa de Janus. Esta invención también está dirigida a composiciones que comprend en métodos para hacer dichos compuestos, y métodos para tratar y preven ir condiciones mediadas por JAK.

Fluoro-pyridinone derivatives useful as antibacterial agents

The disclosure relates to a class of fluoro-pyridinone derivatives of general structure I, wherein R1, R2, R3, T, D and E are as defined in the specification. The disclosure also relates to their use as LpxC inhibitors and to treat bacterial infections. Example compounds include: 4-{ 5-fluoro-4-[2-fluoro-3-(hydroxymethyl)phenyl]-2-oxopyridin-1(2H)-yl} -N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide, 4-[4-(3-ethoxyphenyl)-5-fluoro-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide, 4-(5-chloro-5’-fluoro-2’-oxo-2,4’-bipyridin-1’(2’H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide, 4-{ 4-[4-(1-cyano-1-methylethyl)phenyl]-5-fluoro-2-oxopyridin-1(2H)-yl} -N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide, (2R)-4-(5-fluoro-2-oxo-4-quinoxalin-6-ylpyridin-1(2H)-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide, (2R)-4-[5-fluoro-4-{ 4-[(trans-4-hydroxycyclohexyl)methoxy]phenyI} -2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide.

Fluoro-pyridinone derivatives useful as antibacterial agents

The present invention is directed to a compound to Formula I derivatives, their use as LpxC inhibitors and, more specifically, their use to treat bacterial infections. (see formula I)

Fluoro-pyridinone derivatives useful as antibacterial agents

The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors and, more specifically, their use to treat bacterial infections.

Coronavirus vaccine

This disclosure relates to the field of RNA to prevent or treat coronavirus infection. In particular, the present disclosure relates to methods and agents for vaccination against coronavirus infection and inducing effective coronavirus antigen-specific immune responses such as antibody and/or T cell responses. Specifically, in one embodiment, the present disclosure relates to methods comprising administering to a subject RNA encoding a peptide or protein comprising an epitope of SARS-CoV-2 spike protein (S protein) for inducing an immune response against coronavirus S protein, in particular S protein of SARS-CoV-2, in the subject, i.e., vaccine RNA encoding vaccine antigen.

大腸菌ＦｉｍＨ変異体およびその使用

【課題】改善された生化学的特性および免疫原性をもたらす大腸菌（Ｅ．ｃｏｌｉ）突然変異ＦｉｍＨポリペプチドの設計、そのようなポリペプチドを含む組成物、ならびにこれらの使用を提供する。【解決手段】野生型ＦｉｍＨポリペプチドのアミノ酸配列と比べた少なくとも１個のアミノ酸突然変異を含む、突然変異したＦｉｍＨポリペプチド、および薬学的に許容できる担体を含む医薬組成物とする。【選択図】なし

Escherichia coli compositions and methods thereof

In one aspect, the invention relates to a polypeptide derived from E. coli and a fragment thereof, including compositions and methods thereof. Also disclosed herein are compositions that include a polypeptide derived from E. coli and a fragment thereof; and modified O-polysaccharide molecules derived from E. coli lipopolysaccharides and conjugates thereof. In a further aspect, disclosed herein are mammalian host cells that include sequence(s) encoding a polypeptide derived from E. coli or fragments thereof.

Methods of protecting rna

The present disclosure provides methods of protecting ribonucleic acid (RNA) from degradation under certain conditions by contacting the RNA with an amino acid. The present disclosure also provides compositions comprising such amino acid(s) and RNA.

Composiciones de escherichia coli y metodos de las mismas.

En un aspecto, la invención se relaciona con un polipéptido derivado de E. coli y un fragmento del mismo, incluyendo composiciones y métodos del mismo. También se divulgan aquí composiciones que incluyen un polipéptido derivado de E. coli y un fragmento del mismo; y moléculas de polisacáridos O modificados derivados de lipopolisacáridos de E. coli y conjugados de los mismos. En otro aspecto, se divulgan en el presente documento células huésped de mamíferos que incluyen secuencia(s) que codifican un polipéptido derivado de E. coli o fragmentos del mismo.

Mutantes de proteina f de rsv

Referido a mutantes de proteina F del virus sincicial respiratorio (RSV) de tipo silvestre, cuyo mutante comprende polipeptidos F1 y F2, en donde el mutante comprende al menos una mutacion de aminoacidos introducida relativa a la secuencia de aminoacidos de la proteina F de RSV de tipo silvestre, y la mutacion de aminoacidos introducida comprende: (i) el par de mutaciones de cisteina 155C y 290C y (ii) una o mas mutaciones de cavidad de carga seleccionadas del grupo que consiste en: (1) sustitucion del aminoacido en la posicion 62 con I, Y, L, H o M; (2) sustitucion del aminoacido en la posicion 190 con I; (3) sustitucion del aminoacido en la posicion 54, 58, 189, 219 o 397 con I, Y, L, H o M; (4) sustitucion del aminoacido en la posicion 151 con A o H; (5) sustitucion del aminoacido en la posicion 147 o 298 con I, L, H o M; y (6) sustitucion del aminoacido en la posicion 164, 187, 192, 207, 220, 296, 300 o 495 con I, Y, H; y en donde las posiciones de los aminoacidos estan numeradas de acuerdo a la SEQ ID NO: 1. Tambien se refiere a una molecula de acido nucleico que comprende una secuencia de nucleotidos que codifica una secuencia de aminoacidos del mutante de proteina F de RSV, y una composicion farmaceutica que comprende dicho mutante de proteina F de RSV y un portador farmaceuticamente aceptable como la vacuna.

Self-amplifying rna encoding an influenza virus antigen

Self-amplifying RNA (saRNA) molecules encoding an influenza virus antigen and methods of use thereof are disclosed herein.

Human cytomegalovirus gb polypeptide

The present invention relates to polypeptides and cytomegalovirus (CMV) antigens that include at least two introduced amino acid mutations relative to the amino acid sequence of the wild-type HCMV glycoprotein B (gB). In some embodiments, the polypeptide is stabilized in a conformation alternative to the gB postfusion conformation. Also disclosed are compositions including the polypeptides and uses thereof.

Self-amplifying rna encoding an influenza virus antigen

Self-amplifying RNA (saRNA) molecules encoding an influenza virus antigen and methods of use thereof are disclosed herein.

RSV F protein mutants

RSV F PROTEIN MUTANTS ABSTRACT The present disclosure relates to RSV F protein mutants, nucleic acids or vectors 5 encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and compositions.

RSV F protein mutants

RSV F PROTEIN MUTANTS ABSTRACT The present disclosure relates to RSV F protein mutants, nucleic acids or vectors 5 encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and compositions.

Human cytomegalovirus GB polypeptide

The present invention comprises mutants of a wild-type cytomegalovirus (CMV) glycoprotein B (gB) protein that include at least two introduced amino acid mutations relative to the amino acid sequence of the wild-type HCMV glycoprotein B (gB), compositions including the mutants and uses thereof. In some embodiments, the mutant is stabilized in a conformation alternative to the gB postfusion conformation.

Rsv f protein mutants

The present disclosure relates to RSV F protein mutants, nucleic acids or vectors encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and com positions.

Rsv f protein mutants

The present disclosure relates to RSV F protein mutants, nucleic acids or vectors encoding a RSV F protein mutant, compositions comprising a RSV F protein mutant or nucleic acid, and uses of the RSV F protein mutants, nucleic acids or vectors, and compositions.

Ακρυλαμιδια πυρρολο[2,3-d]πυριμιδινυλιου, πυρρολo[2,3-β]πυραζινυλιου και πυρρολο[2,3-d]πυριδινυλιου

Η παρούσα εφεύρεση παρέχει φαρμακευτικώς ενεργά ακρυλαμίδια πυρρολο[2,3-d]πυριμιδινυλίου και πυρρολο[2,3-d]πυριδινυλίου και ανάλογα εξ' αυτών. Τέτοιες ενώσεις είναι χρήσιμες για αναστολή της Κινάσης Janus [Ιανός] (JAK). Αυτή η εφεύρεση απευθύνεται επίσης και σε συνθέσεις περιλαμβάνοντας μεθόδους για παρασκευή τέτοιων ενώσεων, και μεθόδους για αγωγή και πρόληψη καταστάσεων που μεσολαβούνται από JAK.

Methods of Protecting RNA

The present disclosure provides methods of protecting ribonucleic acid (RNA) from degradation under certain conditions by contacting the RNA with an amino acid. The present disclosure also provides compositions comprising such amino acid(s) and RNA.

Lipid compounds and uses thereof

Compounds are provided having the following structure: (I) or a pharmaceutically acceptable salt, N-oxide, tautomer or stereoisomer thereof, wherein R1, G1, W and m, n, o and p are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a nucleic acid, compositions comprising the compounds and methods for their use and preparation are also provided.

Mutantes de proteina f de rsv

La presente invencion se refiere a mutantes de una proteina F de RSV de tipo silvestre y del subtipo A o B, los cuales comprenden un polipeptido F1 y F2 y mutaciones de aminoacidos introducidas relativas a la proteina F de RSV de tipo silvestre, por ejemplo, un par de mutaciones de cisteina que consiste en: 103C y 148C. Asimismo, las posiciones de los aminoacidos de esta proteina estan numeradas de acuerdo a la SEQ ID NO: 1. Tambien, refiere a los usos de moleculas de acido nucleico y vectores que codifican a los presentes mutantes y composiciones farmaceuticas, que comprenden un primer y segundo mutante, en donde el extremo C-terminal del polipeptido F1 del primer mutante de la proteina F del RSV de subtipo A y el extremo C-terminal del polipeptido F1 del segundo mutante de la proteina F del RSV de subtipo B, esta cada uno enlazado a un dominio plegado de fibritina del fago T4.

Composições de escherichia coli e seus métodos

A presente invenção refere-se, em um aspecto, a um polipeptídeo derivado de E. coli e um fragmento do mesmo, incluindo suas composições e seus métodos. A invenção também se refere a composições que incluem um polipeptídeo derivado de E. coli e um fragmento do mesmo; e moléculas de O-polissacarídeo modificadas derivadas de lipopolissacarídeos de E. coli e seus conjugados. Em um outro aspecto, são fornecidas na presente invenção células hospedeiras de mamífero que incluem sequências que codificam um polipeptídeo derivado de E. coli ou fragmentos do mesmo. Escherichia coli.

Rsv f protein mutants

Polipeptídeo da gb do citomegalovírus humano

POLIPEPTÍDEO DA GB DO CITOMEGALOVÍRUS HUMANO. A presente invenção refere-se a polipeptídeos e antígenos do citomegalovírus (CMV) que incluem pelo menos duas mutações de aminoácido intriduzidas em relação à sequência de acminoácido da glicoproteína B (gB) do HCMV tipo selvagem. Em algumas modalidades, o polipeptídeo é estabilizado em uma conformação alternativa à conformação pós-fusão da gB. Da mesma forma descritos são as composições incluindo polipeptídeos e usos dos mesmos.

E. coli fimh mutants and uses thereof

This disclosure relates to the design of

Mutantes de fimh de e. coli y su uso

Esta divulgacion se refiere al diseno de polipeptidos FimH mutados de E.coli que resulta en propiedades bioquimicas mejoradas e inmunogenecidad, a composiciones que comprenden dichos polipeptidos y a sus usos.

Mutantes de fimh de e. coli y su uso.

Esta divulgación se refiere al diseño de polipéptidos FimH mutados de E.coli que resulta en propiedades bioquímicas mejoradas e inmunogenecidad, a composiciones que comprenden dichos polipéptidos y a sus usos.

Mutantes de fimh de e. coli y su uso

Esta divulgación se refiere al diseño de polipéptidos FimH mutados de E.coli que resulta en propiedades bioquímicas mejoradas e inmunogenecidad, a composiciones que comprenden dichos polipéptidos y a sus usos.

E. coli fimh mutants and uses thereof

This disclosure relates to the design of E. coli mutated FimH polypeptides that result in improved biochemical properties and immunogenicity, compositions comprising such polypeptides, and uses thereof.

Human cytomegalovirus gb polypeptide

The present invention relates to polypeptides and cytomegalovirus (CMV) antigens that include at least two introduced amino acid mutations relative to the amino acid sequence of the wild-type HCMV glycoprotein B (gB). In some embodiments, the polypeptide is stabilized in a conformation alternative to the gB postfusion conformation. Also disclosed are compositions including the polypeptides and uses thereof.

Polipeptido gb de citomegalovirus humano

La presente invencion se relaciona con polipeptidos y antigenos de citomegalovirus (CMV) que incluyen al menos dos mutaciones de aminoacidos introducidas en relacion con la secuencia de aminoacidos de glicoproteina B (gB) de HCMV de tipo silvestre. En algunas modalidades, el polipeptido se estabiliza en una conformacion alternativa para la conformacion de gB posterior a la fusion. Tambien se describen composiciones que incluyen los polipeptidos y usos de los mismos

Polipeptido gb de citomegalovirus humano.

La presente invención se relaciona con polipéptidos y antígenos de citomegalovirus (CMV) que incluyen al menos dos mutaciones de aminoácidos introducidas en relación con la secuencia de aminoácidos de glicoproteína B (gB) de HCMV de tipo silvestre. En algunas modalidades, el polipéptido se estabiliza en una conformación alternativa para la conformación de gB posterior a la fusión. También se describen composiciones que incluyen los polipéptidos y usos de los mismos.

Human cytomegalovirus gb polypeptide

The present invention relates to polypeptides and cytomegalovirus (CMV) antigens that include at least two introduced amino acid mutations relative to the amino acid sequence of the wild-type HCMV glycoprotein B (gB). In some embodiments, the polypeptide is stabilized in a conformation alternative to the gB postfusion conformation. Also disclosed are compositions including the polypeptides and uses thereof.

Human cytomegalovirus gB polypeptide

The present invention relates to polypeptides and cytomegalovirus (CMV) antigens that include at least two introduced amino acid mutations relative to the amino acid sequence of the wild-type HCMV glycoprotein B (gB). In some embodiments, the polypeptide is stabilized in a conformation alternative to the gB postfusion conformation. Also disclosed are compositions including the polypeptides and uses thereof.

Mutantes de proteína f de rsv (virus sincicial respiratorio)

Reivindicación 1: Un mutante de una proteína F de RSV de tipo silvestre, cuyo mutante comprende un polipéptido F1 y un polipéptido F2, caracterizado porque el mutante comprende al menos una mutación de aminoácidos relativa a la secuencia de aminoácidos de la proteína F de RSV de tipo silvestre, y en donde la mutación de aminoácidos se selecciona del grupo que consiste de: (1) una mutación de enlace disulfuro diseñada; (2) una mutación de carga de cavidad; (3) una mutación electrostática; (4) una combinación de al menos una mutación de disulfuro diseñada y al menos una mutación de carga de cavidad; (5) una combinación de al menos una mutación de disulfuro diseñada y al menos una mutación electrostática; (6) una combinación de al menos una mutación de carga de cavidad y al menos una mutación electrostática; y (7) una combinación de al menos una mutación de disulfuro diseñada, al menos una mutación de carga de cavidad, y al menos una mutación electrostática. Reivindicación 6: El mutante de acuerdo con cualquiera de las reivindicaciones 1 - 5, caracterizado porque la mutación de disulfuro diseñada se selecciona del grupo que consiste de: S55C y L188C; S155C y S290C; T103C y L148C; y L142C y N371C. Reivindicación 18: Una composición farmacéutica caracterizada porque comprende (i) un mutante de proteína F de RSV de acuerdo con cualquiera de las reivindicaciones 1 - 17 y (ii) un portador farmacéuticamente aceptable. Reivindicación 23: Un método para reducir la infección por RSV en un humano, caracterizado porque comprende administrar al sujeto una cantidad efectiva de la vacuna de conformidad con la reivindicación 22.

Rsv f protein mutants

Human cytomegalovirus gB polypeptide

The present invention relates to polypeptides and cytomegalovirus (CMV) antigens that include at least two introduced amino acid mutations relative to the amino acid sequence of the wild-type HCMV glycoprotein B (gB). In some embodiments, the polypeptide is stabilized in a conformation alternative to the gB postfusion conformation. Also disclosed are compositions including the polypeptides and uses thereof.

Polynucleotide compositions and uses thereof

The invention relates to RNA molecules encoding an E. coli fimbrial H antigen (FimH). The present disclosure further relates to compositions comprising the RNA molecules formulated in a lipid nanoparticle (RNA-LNP). The present disclosure further relates to the use of the RNA 5molecules, RNA-LNPs and compositions for the prevention of E.coli infection, including urinary tract infection.

Polipéptido gb de citomegalovirus humano

Se describen polipéptidos y antígenos de citomegalovirus (CMV) que incluyen al menos dos mutaciones de aminoácidos introducidas en relación con la secuencia de aminoácidos de glicoproteína B (gB) de HCMV de tipo silvestre. En algunas modalidades, el polipéptido se estabiliza en una conformación alternativa para la conformación de gB posterior a la fusión. También se describen composiciones que incluyen los polipéptidos y usos de los mismos. Se describe un mutante de una proteína de glicoproteína B (gB) de citomegalovirus (CMV) de tipo silvestre, comprende al menos dos mutaciones de aminoácidos en relación con la secuencia de aminoácidos de la proteína gB de CMV de tipo silvestre y en donde la mutación de aminoácidos se selecciona del grupo que consiste de: (i) una mutación de enlace disulfuro diseñada; (ii) una mutación adicional; y (iii) una combinación de al menos una mutación de enlace disulfuro diseñada y al menos una mutación adicional. Se describe una composición / vacuna farmacéutica que comprende (i) un mutante de proteína gB de CMV y (ii) un portador farmacéuticamente aceptable. Se describen métodos para reducir la infección por CMV, obtener una respuesta inmune contra la infección por CMV, o prevenir la infección por CMV en un sujeto que comprende administrar al sujeto una cantidad efectiva de la composición / vacuna.

Composiciones de polinucleotidos y sus usos

La invención se refiere a moléculas de ARN que codifican un antígeno fimbrial H de E. coli (FimH). La presente divulgación se refiere además a composiciones que comprenden las moléculas de ARN formuladas en una nanopartícula lipídica (ARN-LNP). La presente divulgación se refiere además al uso de las moléculas de ARN, las ARN-LNP y las composiciones para la prevención de la infección por E. coli, incluyendo la infección del tracto urinario.

Polynucleotide compositions and uses thereof

The invention relates to RNA molecules encoding an E. coli fimbrial H antigen (FimH). The present disclosure further relates to compositions comprising the RNA molecules formulated in a lipid nanoparticle (RNA-LNP). The present disclosure further relates to the use of the RNA 5molecules, RNA-LNPs and compositions for the prevention of E.coli infection, including urinary tract infection.

Coronavirus vaccine

This disclosure relates to the field of RNA to prevent or treat coronavirus infection. In particular, the present disclosure relates to methods and agents for vaccination against coronavirus infection and inducing effective coronavirus antigen-specific immune responses such as antibody and/or T cell responses. Specifically, in one embodiment, the present disclosure relates to methods comprising administering to a subject RNA encoding a peptide or protein comprising an epitope of SARS-CoV-2 spike protein (S protein) for inducing an immune response against coronavirus S protein, in particular S protein of SARS-CoV-2, in the subject, i.e., vaccine RNA encoding vaccine antigen.

Vaccines against respiratory diseases

The present disclosure relates to hMPV F, PIV3 F and PIV1 F protein mutants, nucleic acids or vectors encoding a hMPV F, PIV3 F and PIV1 F protein mutant, compositions comprising a hMPV F, PIV3 F and PIV1 F protein mutant or nucleic acid, and uses of the hMPV F, PIV3 F and PIV1 F protein mutants, nucleic acids or vectors, and compositions.

Polynucleotide compositions and uses thereof

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl, pyrrolo[2,3-b]pyridinyl acrylamides and epoxides thereof

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3- b]pyrazinyl,and pyrrolo[2,3-b]pyridinyl acrylamides, epoxides,and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

Nucleic acids and uses thereof

Self-amplifying RNA (saRNA) molecules encoding an influenza virus antigen and methods of use thereof are disclosed herein.

Vaccines against respiratory diseases

The present disclosure relates to hMPV F, PIV3 F and PIV1 F protein mutants, nucleic acids or vectors encoding a hMPV F, PIV3 F and PIV1 F protein mutant, compositions comprising a hMPV F, PIV3 F and PIV1 F protein mutant or nucleic acid, and uses of the hMPV F, PIV3 F and PIV1 F protein mutants, nucleic acids or vectors, and compositions.

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides

The present invention provides a method for treating alopecia using certain pharmaceutically active pyrrolo[2,3-d]pyrimidinyl acrylamides having the structure:or a pharmaceutically acceptable salt thereof, as set forth in the Description.

Polipéptido gb de citomegalovirus humano

La presente invención se relaciona con polipéptidos y antígenos de citomegalovirus (CMV) que incluyen al menos dos mutaciones de aminoácidos introducidas en relación con la secuencia de aminoácidos de glicoproteína B (gB) de HCMV de tipo silvestre. En algunas modalidades, el polipéptido se estabiliza en una conformación alternativa para la conformación de gB posterior a la fusión. También se describen composiciones que incluyen los polipéptidos y usos de los mismos.

Modulating the innate immunity of rna

The present disclosure provides methods and compositions for modulating the innate immunity to exogenous ribonucleic acid (RNA) when administered to a subject in need thereof. More particularly, the disclosure provides compositions comprising RNA encoding at least one antigen or therapeutic protein, and at least one compound that modulates the innate immunity to such RNA when administered to a subject in need thereof. The disclosure further provides methods of using such compounds to modulate the innate immunity of such compositions.

Rsv f protein mutants

Usos de um mutante de uma proteína da glicoproteína b (gb) do citomegalovírus (cmv) tipo selvagem ou composição que compreende o mutante, kit, vetor, célula hospedeira

A presente invenção refere-se a polipeptídeos e antígenos do citomegalovírus (CMV) que incluem pelo menos duas mutações de aminoácido intriduzidas em relação à sequência de acminoácido da glicoproteína B (gB) do HCMV tipo selvagem. Em algumas modalidades, o polipeptídeo é estabilizado em uma conformação alternativa à conformação pós-fusão da gB. Da mesma forma descritos são as composições incluindo polipeptídeos e usos dos mesmos.

Polynucleotide compositions and uses thereof

The invention relates to RNA molecules encoding an E. coli fimbrial H antigen (FimH). The present disclosure further relates to compositions comprising the RNA molecules formulated in a lipid nanoparticle (RNA-LNP). The present disclosure further relates to the use of the RNA 5molecules, RNA-LNPs and compositions for the prevention of E.coli infection, including urinary tract infection.

Composiciones de polinucleotidos y sus usos

Referido a una molecula de polinucleotido de acido ribonucleico (ARN) que comprende al menos un marco abierto de lectura (ORF) que codifica un polipeptido antigenico de FimH; en donde el polipeptido de FimH tiene al menos un 90 %, 95, 96 %, 97 %, 98 % o 99 % de identidad con la secuencia de aminoacidos seleccionada entre SEQ ID NO: 1 a 64. En donde el ARN esta fusionado a un dominio dirigido a la membrana del extremo C-terminal por un enlazador. Una composicion que comprende la molecula de ARN, en la que la molecula de ARN esta formulada en una nanoparticula lipidica (ARN-LNP). Tambien se refiere a un metodo para inducir la respuesta inmune contra la infeccion por E. coli, la fabricacion de vacunas de acido ribonucleico que comprenden moleculas de polinucleotidos, y su uso en el tratamiento o prevencion de infeccion del tracto urinario.

Composiciones de polinucleotidos y usos de los mismos.

La invención se relaciona con moléculas de ARN que codifican un antígeno fimbrial H de E.coli, antígeno fimbrial H (FimH). La presente descripción además se relaciona con composiciones que comprenden las moléculas de ARN formuladas en una nanopartícula lipídica (RNA-LNP). La presente descripción además se relaciona con el uso de las moléculas de ARN 5, RNA-LNPs y composiciones para la prevención de la infección de E.coli, incluyendo la infección del tracto urinario.