Patents Assigned to Metabolix, Inc.
  • Patent number: 7026526
    Abstract: Methods and constructs for the introduction of multiple genes into plants using a single transformation event are described. Constructs contain a single 5? promoter operably linked to DNA encoding a modified intein splicing unit. The splicing unit is expressed as a polyprotein and consists of a first protein fused to an intein fused to a second protein. The splicing unit has been engineered to promote excision of all non-essential components in the polyprotein but prevent the ligation reactions normally associated with protein splicing. Additional genetic elements encoding inteins and additional proteins can be fused in frame to the 5?-terminus of the coding region for the second protein to form a construct for expression of more than two proteins. A single 3? termination sequence, such as a polyadenylation sequence when the construct is to be expressed in eucaryotic cells, follows the last coding sequence.
    Type: Grant
    Filed: February 9, 2001
    Date of Patent: April 11, 2006
    Assignee: Metabolix, Inc.
    Inventor: Kristi D. Snell
  • Patent number: 7001969
    Abstract: Methods of forming intermediates from PHAs are disclosed.
    Type: Grant
    Filed: December 21, 2004
    Date of Patent: February 21, 2006
    Assignee: Metabolix Inc.
    Inventors: Luhua Zhong, Edward M. Muller, James J. Barber, Joseph Pugach
  • Patent number: 6933404
    Abstract: In some embodiments, this invention relates to a method that includes contacting a PHA with an aprotic catalyst to form an ester. The ester has only one monomer unit from the PHA. In certain embodiments, this invention relates to a method that includes treating a PHA-containing non-lyophilized biomass to form an ester, and removing at least some of the ester from the biomass.
    Type: Grant
    Filed: December 18, 2002
    Date of Patent: August 23, 2005
    Assignee: Metabolix Inc.
    Inventors: Luhua Zhong, Edward M. Muller, James J. Barber, Joseph Pugach, Robert S. Whitehouse, Sean K. Daughtry
  • Patent number: 6913911
    Abstract: Transgenic microbial strains are provided which contain the genes required for PHA formation integrated on the chromosome. The strains are advantageous in PHA production processes, because (1) no plasmids need to be maintained, generally obviating the required use of antibiotics or other stabilizing pressures, and (2) no plasmid loss occurs, thereby stabilizing the number of gene copies per cell throughout the fermentation process, resulting in homogeneous PHA product formation throughout the production process. Genes are integrated using standard techniques, preferably transposon mutagenesis. In a preferred embodiment wherein mutiple genes are incorporated, these are incorporated as an operon. Sequences are used to stabilize mRNA, to induce expression as a function of culture conditions (such as phosphate concentration), temperature, and stress, and to aid in selection, through the incorporation of selection markers such as markers conferring antibiotic resistance.
    Type: Grant
    Filed: June 13, 2003
    Date of Patent: July 5, 2005
    Assignee: Metabolix, Inc.
    Inventors: Gjalt W. Huisman, Oliver P. Peoples, Frank A. Skraly
  • Patent number: 6897338
    Abstract: Methods of forming acrylic acid from a PHA, such as, for example, poly 3-hydroxypropionate or a 3-hydroxypropionate containing polymer are disclosed. The methods can include, for example, heating a biomass containing the PHA to form acrylic acid. The methods can include, for example, heating the PHA to a temperature of at least about 200° C. to form acrylic acid. The methods can include for example, heating a mixture containing a first portion of the PHA to form a first portion of acrylic acid, and then adding a second portion of the PHA to the mixture.
    Type: Grant
    Filed: December 18, 2002
    Date of Patent: May 24, 2005
    Assignee: Metabolix, Inc.
    Inventors: Luhua Zhong, Robert S. Whitehouse
  • Publication number: 20050101760
    Abstract: Methods of forming intermediates from PHAs are disclosed.
    Type: Application
    Filed: December 21, 2004
    Publication date: May 12, 2005
    Applicant: Metabolix Inc.
    Inventors: Luhua Zhong, Edward Muller, James Barber, Joseph Pugach
  • Patent number: 6878758
    Abstract: Biocompatible polyhydroxyalkanoate compositions with controlled degradation rates have been developed. In one embodiment, the polyhydroxyalkanoates contain additives to alter the degradation rates. In another embodiment, the polyhydroxyalkanoates are formed of mixtures of monomers or include pendant groups or modifications in their backbones to alter their degradation rates. In still another embodiment, the polyhydroxyalkanoates are chemically modified. Methods for manufacturing the devices which increase porosity or exposed surface area can be used to alter degradability. For example, as demonstrated by the examples, porous polyhydroxyalkanoates can be made using methods that creates pores, voids, or interstitial spacing, such as an emulsion or spray drying technique, or which incorporate leachable or lyophilizable particles within the polymer. Examples describe poly(4HB) compositions including foams, coatings, meshes, and microparticles.
    Type: Grant
    Filed: March 28, 2003
    Date of Patent: April 12, 2005
    Assignee: Metabolix, Inc.
    Inventors: David P. Martin, Frank Skraly, Simon F. Williams
  • Patent number: 6867247
    Abstract: Devices formed of or including biocompatible polyhydroxyalkanoates are provided with controlled degradation rates, preferably less than one year under physiological conditions. Preferred devices include sutures, suture fasteners, meniscus repair devices, rivets, tacks, staples, screws (including interference screws), bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopedic pins (including bone filling augmentation material), adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats.
    Type: Grant
    Filed: May 1, 2002
    Date of Patent: March 15, 2005
    Assignee: Metabolix, Inc.
    Inventors: Simon F. Williams, David P. Martin, Frank A. Skraly
  • Patent number: 6867248
    Abstract: Biocompatible polyhydroxyalkanoate compositions with controlled degradation rates have been developed. In one embodiment, the polyhydroxyalkanoates contain additives to alter the degradation rates. In another embodiment, the polyhydroxyalkanoates are formed of mixtures of monomers or include pendant groups or modifications in their backbones to alter their degradation rates. In still another embodiment, the polyhydroxyalkanoates are chemically modified. Methods for manufacturing the devices which increase porosity or exposed surface area can be used to alter degradability. For example, as demonstrated by the examples, porous polyhydroxyalkanoates can be made using methods that creates pores, voids, or interstitial spacing, such as an emulsion or spray drying technique, or which incorporate leachable or lyophilizable particles within the polymer. Examples describe poly(4HB) compositions including foams, coatings, meshes, and microparticles.
    Type: Grant
    Filed: March 28, 2003
    Date of Patent: March 15, 2005
    Assignee: Metabolix, Inc.
    Inventors: David P. Martin, Frank Skraly, Simon F. Williams
  • Patent number: 6844447
    Abstract: Methods of forming intermediates from PHAs are disclosed. In general, the methods include forming a pyrrolidone from a PHA, such as poly 4-hydroxybutyrate or a 4-hydroxybutyrate containing polymer. The methods can include, for example, treating (e.g., heating) the PHA to form a pyrrolidone. The methods can include, for example, treating a biomass containing the PHA to form a pyrrolidone. The methods can include, for example, heating the PHA to a temperature of at most about 90° C. to form a pyrrolidone, wherein the percent yield of the pyrrolidone is at least about 50%.
    Type: Grant
    Filed: December 18, 2002
    Date of Patent: January 18, 2005
    Assignee: Metabolix Inc.
    Inventors: Luhua Zhong, Edward M. Muller, James J. Barber, Joseph Pugach
  • Patent number: 6841603
    Abstract: Biodegradable polymer blend compositions are provided which contain oligomeric esters. The oligoester compound can compatibilize blends of two or more biodegradable polymers resulting in excellent ductility and reduced tendency to embrittlement of products produced from therefrom. In a preferred embodiment of the invention, the blend composition comprises a PHA, polycaprolactone (PCL) and one or more oligomeric esters. In another preferred embodiment of the invention, the blend composition comprises a PHA, polybutylenesuccinate-adipate (PBSUA), and one or more oligomeric esters.
    Type: Grant
    Filed: November 16, 2000
    Date of Patent: January 11, 2005
    Assignee: Metabolix, Inc.
    Inventors: Jawed Asrar, Jean R. Pierre
  • Patent number: 6838493
    Abstract: Devices formed of or including biocompatible polyhydroxyalkanoates are provided with controlled degradation rates, preferably less than one year under physiological conditions. Preferred devices include sutures, suture fasteners, meniscus repair devices, rivets, tacks, staples, screws (including interference screws), bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopedic pins (including bone filling augmentation material), adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats.
    Type: Grant
    Filed: February 26, 2002
    Date of Patent: January 4, 2005
    Assignee: Metabolix, Inc.
    Inventors: Simon F. Williams, David P. Martin, Frank A. Skraly
  • Publication number: 20040253693
    Abstract: Coexpression of a polyhydroxyalkanoic acid synthase and a either a fatty acid:acyl-CoA transferase or an acyl-CoA synthetase in cells enables the biosynthesis of polyester materials. Plasmids, bacteria, materials, and methods for the preparation of polyesters are disclosed.
    Type: Application
    Filed: June 14, 2004
    Publication date: December 16, 2004
    Applicant: Metabolix, Inc.
    Inventors: Silke Hein, Brigitte Sohling, Gerhard Gottschalk, Alexander Steinbuchel
  • Patent number: 6828357
    Abstract: Biocompatible polyhydroxyalkanoate compositions with controlled degradation rates have been developed. In one embodiment, the polyhydroxyalkanoates contain additives to alter the degradation rates. In another embodiment, the polyhydroxyalkanoates are formed of mixtures of monomers or include pendant groups or modifications in their backbones to alter their degradation rates. In still another embodiment, the polyhydroxyalkanoates are chemically modified. Methods for manufacturing the devices which increase porosity or exposed surface area can be used to alter degradability. For example, as demonstrated by the examples, porous polyhydroxyalkanoates can be made using methods that creates pores, voids, or interstitial spacing, such as an emulsion or spray drying technique, or which incorporate leachable or lyophilizable particles within the polymer. Examples describe poly(4HB) compositions including foams, coatings, meshes, and microparticles.
    Type: Grant
    Filed: March 28, 2003
    Date of Patent: December 7, 2004
    Assignee: Metabolix, Inc.
    Inventors: David P. Martin, Frank Skraly, Simon F. Williams
  • Publication number: 20040172675
    Abstract: Methods for engineering transgenic organisms that synthesize polyhydroxyalkanoates (PHAs) containing 3-hydroxyhexanoate as comonomer have been developed. These processes are based on genetically engineered bacteria such as Escherichia coli or in plant crops as production systems which include PHA biosynthetic genes from PHA producers. In a preferred embodiment of the method, additional genes are introduced in wild type or transgenic polyhydroxybutyrate (PHB) producers, thereby creating new strains that synthesize 3HH monomers which are incorporated into PHAs. The 3HH monomer preferably is derived in microbial systems using butanol or butyrate as feedstocks, which are precursors of 3-hydroxyhexanoyl-CoA. Pathways for in vivo production of butyrol-CoA specifically encompassing butyryl-CoA dehydrogenase activity are provided.
    Type: Application
    Filed: November 7, 2003
    Publication date: September 2, 2004
    Applicant: Metabolix, Inc.
    Inventors: Lara Madison, Gjalt W. Huisman, Oliver P. Peoples
  • Patent number: 6780911
    Abstract: Molding compositions including low molecular weight polyhydroxyalkanoates are provided. The use of the low molecular weight polyhydroxyalkanoates as a binder in molding compositions provides improved binder removal in the finished molded product, and offers a wide range of physical properties suitable for use in a variety of processing conditions. The composition preferably includes a powdered material, such as a metal powder, ceramic powder, or blend, admixed with a low molecular weight polyhydroxyalkanoate binder. The compositions are useful in powder processing techniques, such as injection molding, slip casting, tape casting, or extrusion. Methods of forming low molecular weight polyhydroxyalkanoates are also described.
    Type: Grant
    Filed: August 21, 2001
    Date of Patent: August 24, 2004
    Assignee: Metabolix, Inc.
    Inventors: Luhua Zhong, Robert S. Whitehouse
  • Patent number: 6770464
    Abstract: The present invention relates to a process for the production of poly (hydroxy fatty acids) as well as recombinant bacterial strains for carrying out the process. In addition, new poly(hydroxy fatty acids) and new substrates for the production of conventional and new poly(hydroxy fatty acids) are described. Moreover, the invention also relates to a DNA fragment, which codes for a PhaE and a PhaC component of the poly(hydroxy fatty acid) synthase from Thiocapsa pfennigii, as well as the corresponding poly (hydroxy fatty acid) synthase protein.
    Type: Grant
    Filed: February 8, 2001
    Date of Patent: August 3, 2004
    Assignee: Metabolix, Inc.
    Inventors: Alexander Steinbüchel, Mathias Liebergesell, Henry Valentin, Andreas Pries
  • Publication number: 20040137586
    Abstract: The gene encoding a 4-hydroxybutyryl-Co A transferase has been isolated from bacteria and integrated into the genome of bacteria also expressing a polyhydroxyalkanoate synthase, to yield an improved production process for 4HB-containing polyhydroxyalkanoates using transgenic organisms, including both bacteria and plants. The new pathways provide means for producing 4HB containing PHAs from cheap carbon sources such as sugars and fatty acids, in high yields, which are stable. Useful strains are obtaining by screening strains having integrated into their genomes a gene encoding a 4HB-CoA transferase and/or PHA synthase, for polymer production. Processes for polymer production use recombinant systems that can utilize cheap substrates. Systems are provided which can utilize amino acid degradation pathways, &agr;-ketoglutarate, or succinate as substrate.
    Type: Application
    Filed: February 6, 2004
    Publication date: July 15, 2004
    Applicant: Metabolix, Inc.
    Inventors: Gjalt W. Huisman, Frank Skraly, David P. Martin, Oliver P. Peoples
  • Patent number: 6759219
    Abstract: Coexpression of a polyhydroxyalkanoic acid synthase and either a fatty acid: acyl-CoA transferase or an acyl-CoA synthetase in cells enables the biosynthesis of polyester materials. Plasmids, bacteria, materials, and methods for the preparation of polyesters are disclosed.
    Type: Grant
    Filed: September 3, 1999
    Date of Patent: July 6, 2004
    Assignee: Metabolix, Inc.
    Inventors: Silke Hein, Brigitte Söhling, Gerhard Gottschalk, Alexander Steinbüchel
  • Patent number: 6753384
    Abstract: A polyurethane is described which is a reaction product of at least one isocyanate containing material having at least two isocyanate groups and at least one compound having at least two hydrogen atoms capable of reacting with the isocyanate. The compound having the at least two hydrogen atoms contains a hydroxyalkanoate, which is preferably a thermally decomposable or a biodegradable polyhydroxyalkanoate. The polyurethane of the present invention can be used in a number of applications and preferably has improved properties such as, but not limited to, improved flexibility and/or improved hydrophobicity. The polyurethanes of the present invention are preferably biodegradable and easily recycled.
    Type: Grant
    Filed: July 13, 2001
    Date of Patent: June 22, 2004
    Assignee: Metabolix, Inc.
    Inventors: Robert S. Whitehouse, Sean Daughtry, Luhua Zhong