Abstract: An activated, substantially water-soluble poly(ethylene glycol) is provided having of a linear or branched poly(ethylene glycol) backbone and at least one terminus linked to the backbone through a hydrolytically stable linkage, wherein the terminus is branched and has proximal reactive groups. The free reactive groups are capable of reacting with active moieties in a biologically active agent such as a protein or peptide thus forming conjugates between the activated (polyethylene glycol) and the biologically active agent.

Abstract: The invention provides reagents and methods for conjugating a polymer specifically to the ?-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 ?-amine of a polypeptide having a cytokine 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.

Abstract: The invention provides a sterically hindered polymer that comprises a water-soluble and non-peptidic polymer backbone having at least one terminus covalently bonded to an alkanoic acid or alkanoic acid derivative, wherein the carbon adjacent to the carbonyl group of the acid or acid derivative group has an alkyl or aryl group pendent thereto. The steric effects of the alkyl or aryl group allow greater control of the hydrolytic stability of polymer derivatives. The polymer backbone may be poly(ethylene glycol).

Abstract: The invention provides a method for preparing a 1-benzotriazolylcarbonate ester of a water-soluble and non-peptidic polymer by reacting a terminal hydroxyl group of a water-soluble and non-peptidic polymer with di(1-benzotriazolyl)carbonate in the presence of an amine base and an organic solvent. The polymer backbone can be poly(ethylene glycol). The 1-benzotriazolylcarbonate ester can then be reacted directly with a biologically active agent to form a biologically active polymer conjugate or reacted with an amino acid, such as lysine, to form an amino acid derivative.

Abstract: The present invention is directed to maleamic acid derivatives of water soluble polymers, to chemically stable water-soluble polymer succinamic acid-active agent conjugates, and to methods for reproducibly preparing, characterizing and using such polymer reagents and their conjugates.

Abstract: The invention provides a multi-arm block copolymer for use in delivering a variety of bioactive agents. The copolymer of the invention contains a central core from which extend multiple (3 or more) copolymer arms. Each copolymer arm possesses an inner polypeptide segment and an outer hydrophilic polymer segment. Thus, the overall structure of the copolymer comprises an inner core region that includes the central core and the inner polypeptide segment, while the outer core region is hydrophilic in nature. The multi-arm copolymer of the invention is particularly useful for delivery of biologically active agents that can be entrapped within the inner core region.

Abstract: The present invention provides both crosslinked polymer compositions capable of forming hydrogel upon exposure to an aqueous environment and thiosulfonate hydrogel-forming components. The thiosulfonate hydrogel-forming components of the invention are preferably multi-arm thiosulfonate polymer derivatives that form a crosslinked polymer composition when exposed to a base without requiring the presence of a second cross-linking reagent, redox catalyst, or radiation. Methods for forming hydrogel compositions, as well as methods for using the hydrogel, are also provided.

Abstract: The invention provides methods for making copolymers and multi-arm block copolymers useful as drug delivery vehicles. The multi-arm block copolymers comprise a central core molecule, such as a residue of a polyol, and at least three copolymer arms covalently attached to the central core molecule, each copolymer arm comprising an inner hydrophobic polymer segment covalently attached to the central core molecule and an outer hydrophilic polymer segment covalently attached to the hydrophobic polymer segment, wherein the central core molecule and the hydrophobic polymer segment define a hydrophobic core region. The solubility of hydrophobic biologically active agents can be improved by entrapment within the hydrophobic core region of the block copolymer. The invention further includes pharmaceutical compositions including such block copolymers, pharmaceutical compositions, and methods of using the block copolymers as drug delivery vehicles.

Abstract: A water soluble polymer is provided having two or more oligomers linked to each other by hydrolytically degradable carbonate linkages. The polymer can be hydrolytically degraded into oligomers (e.g., oligomers of ethylene oxide) under physiological conditions. The polymer can be conjugated to biologically active agents such as proteins or peptides to impart improved water solubility, reduced immunogenicity, reduced rate of renal clearance, and increased stability. The polymer is useful in making hydrolytically degradable hydrogels which can be used in drug delivery and related biomedical applications. On example of the polymer is a poly (ether carbonate) of the formula X—O—[(—CH2CH2-O-)n—CO2—]n—(CH2CH2))n -y where X and Y are independently H, alkyl, alkenyl, aryl, or a reactive moiety, and at least one of X and Y is a reactive moiety.

Abstract: An activated, substantially water soluble poly(ethylene glycol) is provided having of a linear or branched poly(ethylene glycol) backbone and at least one terminus linked to the backbone through a hydrolytically stable linkage, wherein the terminus is branched and has proximal reactive groups. The free reactive groups are capable of reacting with active moieties in a biologically active agent such as a protein or peptide thus forming conjugates between the activated poly(ethylene glycol) and the biologically active agent.

Abstract: Polymeric reagents comprising a polymer attached, either directly or through one or more atoms to a ketone or a related functional group such as ketone hydrate, thione, monothiohydrate, dithiohydrate, hemiketal, monothiohemiketal, dithiohemiketal, ketal, or dithioketal are provided. The polymeric reagents are useful for, among other things, forming polymer-active agent conjugates. Related methods, compositions, preparations, and so forth are also provided.

Abstract: The invention provides a sterically hindered polymer that comprises a water-soluble and non-peptidic polymer backbone having at least one terminus covalently bonded to an alkanoic acid or alkanoic acid derivative, wherein the carbon adjacent to the carbonyl group of the acid or acid derivative group has an alkyl or aryl group pendent thereto. The steric effects of the alkyl or aryl group allow greater control of the hydrolytic stability of polymer derivatives. The polymer backbone may be poly(ethylene glycol).

Abstract: Conjugates of a Factor VIII moiety and one or more water-soluble polymers are provided. Typically, the water-soluble polymer is poly(ethylene glycol) or a derivative thereof. Also provided are compositions comprising the conjugates, methods of making the conjugates, and methods of administering compositions comprising the conjugates to a patient.

Abstract: The present invention provides storage stable dry powder compositions of IL-4R. The powder compositions demonstrate superior chemical and physical stability over their solution counterparts, particularly upon storage under varying conditions of temperature and humidity. Moreover, the powders, as prepared, possess good aerosol properties, which are maintained upon storage.

Abstract: Managing packets in a shared memory buffer involves linking buffered packets into a linked list in the order that the packets are written into the shared memory buffer, examining the packets in the order of the linked list to determine which packets are intended for available output links, and then dispatching the oldest packet that is intended for an available output link even if the packet is preceded on the linked list by packets that are older but are intended for unavailable output links. Packets are stored with NEXT pointers that establish the linked list and output link identifiers that identify the intended output links of the packets. The head of the linked list is identified by a linked list HEAD pointer. When a packet is dispatched, the packet is removed from the linked list by adjusting the linked list HEAD pointer or the NEXT pointer of the previous packet.

Abstract: Different levels of service are provided to different types of traffic within a single virtual circuit (VC) by converting the traffic from fixed-length cells to variable-length packets, classifying the packets based on information in the packet headers, associating the packets with a VC, and then implementing class-specific enqueuing and dequeuing of the classified packets on a per-VC basis. Classified packets are dequeued from VC-specific and class-specific queues into VC-specific segmentation and re-assembly (SAR) queues according to an algorithm that is a function of traffic class. The dequeuing algorithm determines the level of service that is provided to the different classes of traffic within each VC. Packets are dequeued from the VC-specific SAR queues and converted back to fixed-length cells according to an algorithm that arbitrates among multiple VC-specific SAR queues.

Abstract: A pool of integers is managed by dividing the pool of integers into groups and initializing, in memory, doubly linked lists related to the groups on an as needed basis in response to requests to allocate integers. If an initialized group of integers no longer includes any allocated integers, the doubly linked list related to the group is deleted from memory. Memory locations of the group-specific doubly linked lists are identified by a hash table that includes a unique hash table pointer for each one of the groups. Each element of the doubly linked list includes a next pointer for identifying a next element and a previous pointer for identifying a previous element. A specific free integer can be allocated in an order of one, O(1), operation by indexing into the linked list and utilizing the next and previous pointers of the linked list element to remove the linked list element from the linked list.

Abstract: Managing a position-dependent data set that is stored in a content addressable memory (CAM) array involves identifying an instance of a base position-dependent data set that exists in software, identifying an instance of an edited position-dependent data set that exists in software, determining differences between the instance of the base position-dependent data set that exists in software and the instance of the edited position-dependent data set that exists in software, and incorporating the differences between the instance of the base position-dependent data set that exists in software and the instance of the edited position-dependent data set that exists in software into an instance of said base position-dependent data set that exists in a CAM array.

Abstract: Multiple techniques for providing failure protection in a network node that includes primary and secondary control modules (CMs) are disclosed. One technique involves synchronizing configuration state information between the CMs by executing a configuration command within the primary CM and then executing the same configuration command within the secondary CM only if executing the configuration command within the primary CM does not cause the primary CM to fail. Another technique involves gleaning table entries from hardware-based forwarding tables and using the gleaned table entries to generate a software-based forwarding table in the secondary CM.

Abstract: The present invention provides storage stable dry powder compositions of IL-4R. The powder compositions demonstrate superior chemical and physical stability over their solution counterparts, particularly upon storage under varying conditions of temperature and humidity. Moreover, the powders, as prepared, possess good aerosol properties, which are maintained upon storage.