Patents

Patents are legal documents drawn up by inventors and lawyers and granted by various patent offices around the world, to protect the inventors' intellectual property. The short description accompanying each patent in this Patents section is therefore taken from the legal document as is, with minor corrections for Greek symbols and obvious spelling errors. The patents included in this section may be for material products (defensins or defensin-like peptides or nucleic acid sequences, synthetic or natural) or for novel methods of detecting, quantitating, synthesizing, or delivering antimicrobial peptides/nucleic acid sequences in general. The curators' criterion for inclusion in this section is broader for novel methods than for material products, in the hope that these methods may in future be similarly applied to defensins.

Patents in which the defensins or defensin-like material products and methods as above are not novel, such as biomarker sets containing unmodified defensin or defensin-like peptides or oligonucleotides, are excluded from this section. The exception to such exclusions is where the patent provides other novel defensin-related material products or methods in addition to those non-novel of the biomarker set itself. This exclusion is because the reasonable presence of defensin or defensin-like sequences or indeed any other sequences in patented biomarker sets is necessarily attributed to some prior discovery of disease state correlation with such sequences. The curators have observed therefore that the novel discovery in biomarker-related patents is often the method of biomarker array analysis and validation as well as its resultant implications for diagnostics and prognostics. The expert evaluation of such biomarker analysis and validation is well outside the scope of the Defensins Knowledgebase. The reader is respectfully referred to a biomarker database specific to the disease to perform his own assessment of the validity of the biomarker.

Methods not pertaining to the antimicrobial activity of defensins, but where defensins or antimicrobial peptides or small cationic peptides or disulphide-bonded peptides or their respective nucleic acid sequences are suggested in some unambiguous detail to play a useful role in the method, with or without supporting experimental evidence, are included as well in this section. Patents in which natural defensins are up/downregulated in a clearly defined signal transduction pathway as a result of the unrelated patented novel compound or method are also included. And lastly, all patents showing experimental work done with defensins or antimicrobial peptides or small cationic peptides or disulphide-bonded peptides or their respective nucleic acid sequences, where such peptides or nucleic acid sequences are not the experimental controls, are included without exception.

The data in this section have been extracted from the academic version of SciFinder Scholar 2007 and from public Google search - a wide range of defensin-related patents are included.

Keywords:

Results 211 - 220 of 333

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Last updated: 20th February 2008

Patents
Patent No.: WO 069900
Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components.
Applicant: Bridon DP, Ezrin AM, Milner PG, Holmes DL, Thibaudeau K (2000)
A method for protecting a peptide from peptidase activity in vivo, the peptide being composed of between 2 and 50 amino acids and having a C-terminus and an N-terminus and a C-terminus amino acid and an N-terminus amino acid is described. In the first step of the method, the peptide is modified by attaching a reactive group to the C-terminus amino acid, to the N-terminus amino acid, or to an amino acid located between the N-terminus and the C-terminus, such that the modified peptide is capable of forming a covalent bond in vivo with a reactive functionality on a blood component. The solid phase peptide synthesis of a no. of derivs. with 3-maleimidopropionic acid (3-MPA) is described. In the next step, a covalent bond is formed between the reactive group and a reactive functionality on a blood component to form a peptide-blood component conjugate, thereby protecting said peptide from peptidase activity. The final step of the method involves the analyzing of the stability of the peptide-blood component conjugate to assess the protection of the peptide from peptidase activity. Thus, the percentage of a K5 kringle peptide (Pro-Arg-Lys-Leu-Tyr-Asp-Lys-NH2) conjugated to human serum albumin via MPA remained relatively const. through a 24-h plasma assay in contrast to unmodified K5 which decreased to 9% of the original amt. of K5 in only 4 h in plasma.

Patent No.: WO 068405
Cloning and cDNA sequences of plant defensins and uses thereof.
Applicant: Miao G-H, Weng Z, Famodu OO (2000)
This invention relates to isolated cDNAs encoding plant defensins. The invention also relates to the construction of a chimeric gene encoding all or a substantial portion of the plant defensin, in sense or antisense orientation, wherein expression of the chimeric gene results in prodn. of altered levels of the plant defensin in a transformed host cell.

Patent No.: WO 068265
Antimicrobial theta-defensins and methods of using same.
Applicant: Selsted ME, Tang Y, Yuan J, Ouellette AJ (2000)
The present invention relates to an isolated cyclic peptide, theta-defensin, having antimicrobial activity, and to theta-defensin analogs. A theta-defensin can have the amino acid sequence Xaal-Xaa2-Xaa3-Xaa4-Xaa5-Xaa1-Xaa6-Xaa4-Xaa4-Xaa1-Xaa1-Xaa6-Xaa4-Xaa5-Xaa1-Xaa3- aa7-Xaa8, wherein Xaa1 to Xaa8 are defined; wherein Xaa1 can be linked through a peptide bond to Xaa8; and wherein crosslinks can be formed between Xaa3 and Xaa3, between Xaa5 and Xaa5, and between Xaa7 and Xaa7. For example, the invention provides a theta-defensin having the amino acid sequence Gly-Phe-Cys-Arg-Cys-Leu-Cys-Arg-Arg-Gly-Val-Cys-Arg-Cys-Ile-Cys-Thr-Arg (SEQ ID NO:1), wherein the Gly at position 1 (Gly-1) is linked through a peptide bond to Arg-18, and wherein disulfide bonds are present between Cys-3 and Cys-16, between Cys-5 and Cys-14, and between Cys-7 and Cys-12. The invention also provides nucleic acids encoding theta-defensins and antibodies that specifically bind a theta-defensin. In addn., the invention relates to methods of using theta-defensin to reduce or inhibit microbial growth or survival.

Patent No.: WO 062736
Low adenosine anti-sense oligonucleotide, compositions, kit and method for treatment of airway disorders associated with bronchoconstriction, lung inflammation, allergy(ies) and surfactant depletion.
Applicant: Nyce JW (2000)
An in vivo method of selectively delivering a nucleic acid to a target gene or mRNA, comprises the topical administration, e.g. to the respiratory system, of a subject of a therapeutic amt. of an oligonucleotide (oligo) that is antisense to the initiation codon region, the coding region, the 5' or 3' intron-exon junctions or regions within 2 to 10 nucleotides of the junctions of the gene or antisense to a mRNA complementary to the gene in an amt. effective to reach the target polynucleotide and reducing or inhibiting expression. In addn. a method of treating an adenosine-mediated effect comprises topically administering to a subject an antisense oligo in an amt. effective to treat the respiratory, pulmonary, or airway disease. In order to minimize triggering adenosine receptors by their metab., the administered oligos have a low content of or are essentially free of adenosine. A pharmaceutical compn. and formulations comprise the oligo antisense to an adenosine receptor, genes and mRNAs encoding them, genomic and mRNA flanking regions, intron and exon borders and all regulatory and functionally related segments of the genes and mRNAs encoding the polypeptides, their salts and mixts. Various formulations contain a requisite carrier, and optionally other additives and biol. active agents. The low-adenosine or adenosine-free (des-A) agent for practicing the method of the invention may be prepd. by selecting a target gene(s), genomic flanking region(s), RNA(s) and/or polypeptide(s) assocd. with a disease(s) or condition(s) afflicting lung airways, obtaining the sequence of the mRNA(s) corresponding to the target gene(s) and/or genomic flanking region(s), and/or RNAs encoding the target polypeptide(s), selecting at least one segment of the mRNA which may be up to 60 % free of thymidine (T) and synthesizing one or more anti-sense oligonucleotide(s) to the mRNA segments which are free of adenosine (A) by substituting a universal base for A when present in the oligonucleotide. The agent may be prepd. by selection of target nucleic acid sequences with GC running stretches, which have low T content, and by optionally replacing A in the antisense oligonucleotides with a "Universal or alternative base". The agent, compn. and formulations are used for prophylactic, preventive and therapeutic treatment of ailments assocd. with impaired respiration, lung allergy(ies) and/or inflammation and depletion lung surfactant or surfactant hypoprodn., such as pulmonary vasoconstriction, inflammation, allergies, allergic rhinitis, asthma, impeded respiration, lung pain, cystic fibrosis, bronchoconstriction. The present treatment is suitable for administration in combination with other treatments, e.g. before, during and after other treatments, including radiation, chemotherapy, antibody therapy and surgery, among others. Alternatively, the present agent is effectively administered prophylactically or therapeutically by itself for conditions without known therapies or as a substitute for therapies exhibiting undesirable side effects. The treatment of this invention may be administered directly into the respiratory system of a subject so that the agent has direct access to the lungs, or by other effective routes of administration, e.g. topically, transdermally, by implantation, etc., in an amt. effective to reduce or inhibit the symptoms of the ailment.

Patent No.: WO 051621
Method for validating/invalidating target(s) and pathways.
Applicant: Nyce JW (2000)
A method of detg. the existence of a correlation between a function of a disease or condition and a gene or mRNA encoding a target polypeptide suspected of being assocd. with a disease or condition, comprises obtaining oligonucleotides (oligos) consisting of up to about 15 % adenosine (A), preferably having no adenosine content, and which is anti-sense to a target selected from the group consisting of target genes and their corresponding mRNAs, genomic and mRNA flanking regions selected from the group consisting of 3' and 5' intron-exon borders and the juxta-section between coding and non-coding regions, and all mRNA segments encoding polypeptides assocd. with a pre-selected disease or condition; selecting amongst the oligos one that significantly inhibits or ablates expression of the polypeptide encoded by the mRNA upon in vitro hybridization to the target mRNA; administering to a subject an amt. of the selected oligo effective for in vivo hybridization to the target mRNA; and assessing a subject's function that is assocd. with the disease or condition before and after administration of the oligo; wherein a change in the function's value greater than about 70% indicates a pos. correlation, between about 40 and about 70% a possible correlation, and below about 30% a lack of correlation. The present method preferably administers the oligos in situ where the target is located, e.g. into the subject's respiration when validating targets assocd. with malignant and other pulmonary and respiratory functions, so that the agent has direct access to the lungs. Alternatively, such desAdenosine oligos may be delivered directly to the CNS or other organs, tissues and organ systems, by known delivery formulations. This invention provides a rapid, reliable method for drug target validation/invalidation in various biol. systems that utilize proprietary low or desAdenosine antisense oligonucleotides. Using desAdenosine antisense oligonucleotides, the present method may validate/invalidate potential gene targets with a level of speed and accuracy that has heretofore been impossible using traditional techniques. The use of antisense oligonucleotides to target adenosine receptors is described. Adenosine A1 receptor antisense oligonucleotides had bronchodilator activity in rabbits and adenosine A3 receptor antisense oligonucleotides had anti-inflammatory activity in asthmatic rabbits.

Patent No.: WO 034312
Method of separating basic peptide or basic protein from fusion protein using hydroxylamine.
Applicant: Park H-B, Pyo S-H, Hwang SW, So J-E, Kim J-H, Kim JH, Hong S-S, Lee H-S (2000)
The present invention relates to a method of recovering basic peptide or basic protein at a high yield from a fusion protein that has a hydroxylamine cleavage site between the basic peptide or basic protein and the fusion partner. More particularly, the present invention is composed of the processes of reacting fusion protein with hydroxylamine at a pH of 7.5 ~ 8.5 and recovering the basic peptide from the reaction mixt. Magainin deriv. MSI-344 was prepd. as a fusion peptide. The fusion product was purified from the culture medium. Then MSI-344 was cleaved using 6M hydroxylamine HCl at pH 8.1.

Patent No.: WO 031279
Efficient methods for producing antimicrobial cationic peptides in host cells.
Applicant: Burian J, Bartfeld D (2000)
Endogenously produced cationic antimicrobial peptides are ubiquitous components of host defenses in mammals, birds, amphibia, insects, and plants. Cationic peptides are also effective when administered as therapeutic agents. A practical drawback in cationic peptide therapy, however, is the cost of producing the agents. The methods described herein provide a means to efficiently produce cationic peptides from recombinant host cells. These recombinantly-produced cationic peptides can be rapidly purified from host cell proteins using anion exchange chromatog.

Patent No.: WO 011196
Dahlia merckii antifungal Dm gene sequences, and their use in producing transgenic plants with microorganism infection resistance.
Applicant: Evans IJ, Ray JA (2000)
Dahlia merckii antifungal Dm gene sequences, and their use in producing transgenic plants with resistance to microorganism infection are described. CDNAs for Dm genes and a mature Dm-AMP1 gene were cloned from Dahlia merckii and sequenced. Recombinant proteins expressed in transgenic tobacco and oil seeds demonstrated antifungal activity. Arabidopsis thaliana transformed with the expression vector for the co-expression of DmAMP1 and RsAFP2 expressed both plant defensins. Transgenic tomato contg. an expression construct of Dahlia merckii antimicrobial protein signal peptide fused with the sweet tasting protein Brazzein gene were also produced, and accumulation of Brazzein was detected. Vector constructs for the transient expression of Dm-AMP were also created, and used to transform black Mexican sweet (BMS) maize cell suspensions.

Patent No.: WO 011175
Using linker peptides containing multiple proteinase cleavage sites to co-express multiple antimicrobial proteins in transgenic plant.
Applicant: Broekaert WF, Francois IEJA, De Bolle MFC, Evans IJ, Ray JA (2000)
To co-express or improve expression levels of two distinct plant defensins DmAMP1 (from dahlia seed) and RsAFP2 (from radish seed), their coding region are linked by coding sequence for peptides contg. proteinase cleavage sites. The proteinase cleavage sites are chosen from Impatiens balsamina Ib-AMP gene protein, C-terminal propeptides of either DmAMP1 precursor or AcAMP2 precursor, picornavirus FMDV 2A or subtilisin-like protease processing sites. Signal peptide are also included in the chimeric polyprotein for post-translational processing in the secretory pathway of plants and individual components to release functional individual components extracellularly. The method can also be applied to express 4 mature antimicrobial proteins.

Patent No.: WO 009525
Low-adenosine antisense oligonucleotide agents, compositions, kits and treatments for respiratory disorders.
Applicant: Nyce JW (2000)
A compn. comprises a nucleic acid comprising an oligo antisense to a target such as polypeptide(s) assocd. with an ailment afflicting lung airways, genes and mRNAs encoding them, genomic and mRNA flanking regions, intron and exon borders and all regulatory and functionally related segments of the genes and mRNAs encoding the polypeptides, their salts and mixts. Various formulations contain a requisite carrier, and optionally other additives and biol. active agents. The agent of the invention may be prepd. by selecting a target gene(s), genomic flanking region(s), RNA(s) and/or polypeptide(s) assocd. with a disease(s) or condition(s) afflicting lung airways, obtaining the sequence of the mRNA(s) corresponding to the target gene(s) and/or genomic flanking region(s), and/or RNAs encoding the target polypeptide(s), selecting at least one segment of the mRNA which may be up to 60% free of thymidine (T) and synthesizing one or more antisense oligonucleotide(s) to the mRNA segments which are free of adenosine (A) by substituting a universal base for A when present in the oligonucleotide. The agent may be prepd. by selection of target nucleic acid sequences with GC running stretches, which have low T content, and by optionally replacing A in the antisense oligonucleotides with a universal base. The agent, compn. and formulations are used for prophylactic, preventive and therapeutic treatment of ailments assocd. with impaired respiration, allergy(ies) and/or inflammation, such as pulmonary vasoconstriction, inflammation, allergies, asthma, impeded respiration, lung pain, cystic fibrosis, bronchoconstriction, pulmonary hypertension and bronchoconstriction, chronic bronchitis, emphysema, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), ischemic conditions including ischemia itself, and cancers such as leukemias, lymphomas, carcinomas, and the like, e.g. colon cancer, breast cancer, pancreatic cancer, lung cancer, hepatocellular carcinoma, kidney cancer, melanoma, hepatic metastasis, etc., as well as all types of cancers with may metastasize or have metastasized to the lung(s), including breast and prostate cancer. The present treatment is suitable for administration in combination with other treatments, e.g. before, during and after other treatments, including radiation, chemotherapy, antibody therapy and surgery, among others. The present agent is effectively administered preventatively, prophylactically or therapeutically by itself for conditions without known therapies, or as a substitute for, or in conjunction with, other therapies exhibiting undesirable side effects. The treatment of this invention may be administered directly into the respiratory system of a subject, so that the agent has direct access to the airways and the lungs. The invention is exemplified with specificity and pharmacokinetic studies using phosphorothioated antisense oligonucleotides targeted to the adenosine receptors A1, A2a, A2b, and A3.