Nektar Therapeutics

Nektar Therapeutics Al, Corporation

Chelsea Therapeutics, Inc.

The University of Arizona

National Institutes of Health, a Component of the US Dept. of Health & Human Services

Applied Research Systems Ars Holding N.v.

Merck Serono S. A.

Laboratoires Serono S.a.

Shearwater Corporation

National Institute of Heatlh

Gas Technology Institute

Gti Energy

Ab-cwt LLC

Michael James Roberts

Terry L Marker

Martin Brendan Linck

Larry Gordon Felix

Michael David Bentley

Zhihao Fang

Antoni Kozlowski

Xiaoming Shen

Lin Cheng

Simon Pedder

Nabil El-Tayar

Milton Harris

Wayne Sawlivich

Michael R Boyd

Myron K Jacobson

Elaine L Jacobson

Barry R O'Keefe

Terry N Adams

Brian S Appel

Toshiyuki Mori

James H Freiss

William F Lange

Georg T Wondrak

Moonsun Kim

Craig Timothy Einfeldt

M Elizabeth Snell

Michael Charles Carnesi

Gerry Rowse

Barry R O'keefe

M K c/oUniversity Of Arizona Jacobson

EL University Of Arizona Jacobson

G T c/oUniversity Of Arizona Wondrak

Isolatable, hydroxyapatite-targeting polymeric structures, and biologically active conjugates thereof, are provided. The polymeric structure includes a linear or branched water-soluble and non-peptidic polymer backbone, such as a PEG backbone, having at least two termini, a first terminus being covalently bonded to a hydroxyapatite-targeting moiety, such as a bisphosphonate, and a second terminus covalently bonded to a chemically reactive group, wherein said chemically reactive group is protected or unprotected. Methods of preparing and using hydroxyapatite-targeting polymeric structures, and biologically active conjugates thereof, are also provided.

Hydroxyapatite-targeting poly(ethylene glycol) and related polymers

The present invention provides combinations of active agents, such combinations comprising one or more antifolate compounds. The particularly can include methotrexate and one or more further antifolate compounds. In specific embodiments, the combinations are useful for treating certain conditions, such as rheumatoid arthritis. The invention also provides articles useful to provide the combinations in desirable dosage forms and combinations. The combinations further may be useful in the treatment of further conditions, including abnormal cell proliferation, inflammatory diseases, asthma, and arthritis.

Antifolate combinations

The invention provides polymer conjugates of opioid antagonists comprising a polymer, such as poly(ethylene glycol), covalently attached to an opioid antagonist. The linkage between the polymer and the opioid antagonist is preferably hydrolytically stable. The invention also includes a method of treating one or more side effects associated with the use of opioid analgesics, such as constipation, nausea, or pruritus, by administering a polymer conjugate of the invention.

Polymer conjugates of opioid antagonists

The present invention is directed to compounds that are specifically structured to provide enzyme inhibition. In specific embodiments, the enzyme inhibiting compounds exhibit antifolate activity. Particularly, the inventive compounds are formed of an antifolate residue that is active in inhibiting one or more of TS, DHFR, GAR, FPGS, and AICAR Tfase. The enzyme inhibiting compounds are useful in a variety of methods of treatment, including treating abnormal cell proliferation and treating inflammation.

Enzyme inhibiting compounds

A substantially hydrophilic conjugate is provided having a peptide that is capable of passing the blood-brain barrier covalently linked to a water-soluble nonpeptidic polymer such as polyethylene glycol. The conjugate exhibits improved solubility and in vivo stability and is capable of passing the blood-brain barrier of an animal.

Polymer stabilized neuropeptides

The present invention provides pharmaceutical compositions comprising droxidopa alone, or in combination with one or more further active ingredients, for the treatment of conditions, such as mood disorders, sleep disorders, or attention deficit disorders. In certain embodiments, the compositions useful in the methods of the invention comprise droxidopa and a compound selected from the group consisting of DOPA decarboxylase inhibiting compounds, catechol-O-methyltransferase inhibiting compounds, cholinesterase inhibiting compounds, monoamine oxidase inhibiting compounds, norepinephrine reuptake inhibiting compounds, selective serotonin reuptake inhibiting compounds, tricyclic antidepressant compounds, serotonin norepinephrine reuptake inhibiting compounds, norepinephrine dopamine reuptake inhibiting compound, noradrenergic and specific serotonergic antidepressants, and combinations thereof. The inventive compositions are particularly useful in the treatment of depression, narcolepsy, insomnia, and Attention Deficit/Hyperactivity Disorder (AD/HD).

Droxidopa and pharmaceutical composition thereof for the treatment of mood disorders, sleep disorders or attention deficit disorders

The invention provides reagents and methods for conjugating a polymer specifically to the &#x3b1;-amine of a polypeptide. The invention provides monofunctional, bifunctional, and multifunctional PEGs and related polymers having a terminal thioester moiety capable of specifically conjugating to the &#x3b1;-amine of a polypeptide having a cysteine or histidine residue at the N-terminus. The invention provides reactive thioester-terminated PEG polymers that have suitable reactivity with an N-terminal cysteine or histidine residue of a polypeptide to produce an amide bond between the PEG molecule and the polypeptide.

Thioester-terminated water soluble polymers and method of modifying the N-terminus of a polypeptide therewith

The present invention provides methods of treating fibromyalgia or other diseases or conditions causing widespread pain and/or fatigue. In particular, the invention provides pharmaceutical compositions comprising droxidopa alone, or in combination with one or more further active agents, that can be used in the inventive methods. The methods of treatment can comprise treating, preventing, reducing, or eliminating a variety of symptoms recognized as indicative of fibromyalgia, such as chronic pain, allodynia, hyperalgesia, fatigue, sleep disturbance, and depression.

Droxidopa and pharmaceutical composition thereof for the treatment of fibromyalgia

The present invention is directed to antifolate compounds having the structure wherein:

Substituted pyrrolo[2,3-d]pyrimidines as antifolates

Hydroxypatite-targeting poly(ethylene glycol) and related polymers

Growing community of inventors

Charlotte, NC, United States of America

Michael James Roberts