Atopic Dermatitis News and Articles

Return to Library

Recent Atopic Dermatitis News and Articles

• Patent Issued for Pharmaceutical Composition Comprising Racemic Aminopterin
• \"Substituted Pyrimidines as Prostaglandin D2 Receptor Antagonists\" in Patent Application Approval Process
• Agency Reviews Patent Application Approval Request for \"Manufacturing Process for Fresh and Frozen Stem Cells\"
• New Dermatitis Study Findings Have Been Reported from Oita University
• New Inflammation Study Findings Have Been Published by Scientists at Federal University
• Patent Application Titled \"Substituted Pyrimidine as a Prostaglandin D2 Receptor Antagonist\" Under Review
• Research from Yonsei University College of Medicine Has Provided New Data on Dermatology
• Patent Issued for Skin-Care Preparations Containing Mupirocin and Betamethasone Dipropionate
• Research from Kyung Hee University in Dermatitis Provides New Insights

---

Patent Issued for Method for Treatment of Inflammatory Disease and Disorder

2013 JAN 21 (NewsRx) -- By a News Reporter-Staff News Editor at Cancer Gene Therapy Week -- According to news reporting originating from Alexandria, Virginia, by NewsRx journalists, a patent by the inventors Braiman-Wiksman, Liora (Le-Zion, IL); Tennenbaum, Tamar (Jerusalem, IL); Sagiv, Yuvai (Gedera, IL); Gartsbein, Marina (Tikva, IL); Brener, Ephraim (Rishon Le Zion, IL); Ben-Hamo, Moshe (Bene Braq, IL); Hammer, Liat (Modiin, IL), filed on July 13, 2011, was cleared and issued on January 8, 2013.

The assignee for this patent, patent number 8349793, is Heal0r, Ltd. (Rehovot, IL).

Reporters obtained the following quote from the background information supplied by the inventors: "Initiation of inflammation begins with an inflammatory response and leads to the activation of neutrophils, granulocytes, monocytes, macrophages, as well as other immunomodulatory cells. This may result in a topical or systemic inflammatory cascade involving inflammatory cytokines and mediators, such as interleukins (ILs), Tumor necrosis factor alpha (TNF.alpha.), and prostaglandins. This complex inflammatory mediated cascade triggers a whole range of responses, such as cellular chemotaxis and endothelial injury and leads to the recruitment of additional cells from the innate and adaptive immune systems.

"The skin serves as an important boundary between the internal body and the environment, preventing contact with potentially harmful pathogens. In the case of antigen/pathogen penetration, an inflammatory response is often induced to eliminate the antigen. This response leads to a dermal infiltrate that consists predominantly of T cells, polymorphonuclear cells, and macrophages.

"The inflammatory response is not necessarily associated with external stimuli, or may be caused by a non-harmful environmental substances (in case of allergies). In both cases an over-expression of proinflammatory cytokines without proper controls leads to inflammation which is the hallmark of topical and systemic inflammation generally, as well as a variety of inflammatory diseases and disorders. Inflammation is associated with a variety of disorders such as eczema and dermatitis, including for example, atopic dermatitis, seborrheic dermatitis, dyshidrotic eczema, nummular dermatitis, stasis dermatitis, allergic dermatitis, psoriasis, pruritis, multiple sclerosis, cutaneous inflammation, cicatricial pemphigoid, scleroderma, hidradenitis suppurativa, toxic epidermal necrolysis, acne, osteitis, graft vs. host disease (GvHD), pyroderma gangrenosum, and Behcet's Syndrome.

"Over production of proinflammatory cytokines has been implicated in many inflammatory and autoimmune diseases. For example, the secretion of cytokines such as TNF.alpha. and Interleukin-23 (IL-23), which stimulates survival and proliferation of Th17 cells, are highly associated with psoriasis, where IL-6 is required for Th17 development in addition to its general role as proinflammatory cytokine. Other cytokines like IL-12 and IP-10 are initiators and involves in Th1 pathway which is typical to psoriasis and other autoimmune diseases. IL-5, a cytokine that increases the production of eosinophils, is over-expressed in asthma resulting in accumulation of eosinophils in the asthmatic bronchial mucosa, a hallmark of allergic inflammation. IL-4 and IL-13 are known mediators of the hypercontractility of smooth muscle found in inflammatory bowel disease and asthma. Additionally, as discussed further below, inflammatory cytokines have been shown to be implicated in, by way of example, psoriasis, multiple sclerosis, arthritis, ischemia, septic shock, and organ transplant rejection.

"Similarly, granulocyte macrophage-colony stimulating factor (GM-CSF) is a regulator of maturation of granulocyte and macrophage lineage population and has been implicated as a key factor in many inflammatory and autoimmune diseases. For example, antibodies that inhibit GM-CSF secretion have been shown to ameliorate autoimmune disease.

"Thus, development of therapeutics that reduce secretion of proinflammatory cytokines and/or regulate immunomodulators would be beneficial in alleviating topical and systemic inflammation generally, as well as a host of inflammatory and/or autoimmune diseases as discussed herein. Several lines of evidence point to modulators of PKC isoforms as useful in achieving these results.

"Several in vivo studies have shown the involvement of T helper (Th) 17 cells as well as secretion of cytokines such as interleukins and TNF.alpha., by skin associated cells such as keratinocytes, dendritic and T helper cells, as key players in the development of the inflammatory response involved in the pathogenesis of psoriasis and other autoimmune inflammatory diseases. The secretion of cytokines such as TNF.alpha. and Interleukin (IL)-23, which stimulates survival and proliferation of Th17 cells, also serves as a key master cytokine regulator for these diseases. (Fitch et al. (2007) Curr Rheumatol Rep. 9:461-7). Th17 cells within dermis in turn, induce secretion of IL-17A and IL-22. IL-22, in particular, derive keratinocyte hyperproliferation and augment the inflammatory response in psoriasis (Fitch et al. (2007) Curr Rheumatol Rep 9:461-7).

"The protein kinase C (PKC) family represents a group of phospholipid dependent enzymes catalyzing the covalent transfer of phosphate from ATP to serine and threonine residues of proteins. The family is currently considered as composed of at least 12 individual isoforms which belong to 3 distinct categories based on their activation by calcium ion(s) and other factors. The PKC family consists of at least ten members, usually divided into three subgroups: classical, novel and atypical PKCs (FIG. 1). The specific cofactor requirements, tissue distribution, and cellular compartmentalization suggest differential functions and the tuning of specific signaling cascades for each isoform. Thus, specific stimuli can lead to differential responses via isoform specific PKC signaling regulated by their factors, such as: expression, localization, and/or phosphorylation status in particular biological settings. PKC isoforms are activated by a variety of extracellular signals and, in turn, modify the activities of cellular proteins including receptors, enzymes, cytoskeletal proteins, and transcription factors. Accordingly, the PKC family plays a central role in cellular signal processing including regulation of cell proliferation, differentiation, survival and death.

"PKC.alpha., which is highly abundant in skin, is the major conventional, Ca.sup.2+ responsive, PKC isoform in epidermis and it was initially the only cPKC detected in the keratinocytes in vitro and in vivo (Dlugosz et al. (1992) Biomed Pharmacother 46:304; Wang et al. (1993) J Cancer Res Clin Oncol 119:279-287). Therefore, PKC.alpha. had been proposed as a key player in Ca.sup.2+ induced differentiation (Denning et al. (1995) Cell Growth Differ 6:149-157; Dlugosz et al. (1992) Biomed Pharmacother 46:304). Being in epidermis and mainly restricted to suprabasal layers (Denning et al. (2004) Int J Biochem Cell Biol 36:1141-1146), PKC.alpha. is involved in cell cycle withdrawal and primarily associated with the keratin cytoskeleton and desmosomal cell-cell junctions (Jansen et al. (2001) Int J Cancer 93:635-643; Tibudan et al. (2002) J Invest Dermatol. 119:1282-1289). Since, upon exposure to the classical PKC activator TPA (12-O-tetradecanoylphorbol-13-acetate), spinous markers were suppressed, PKC.alpha. was thought to be largely responsible for the shift from spinous to granular differentiation as a result of TPA activation (Dlugosz and Yuspa (1993) J Cell Biol 120:217-225; Lee et al. (1998) J Invest Dermatol 111:762-766; Matsui et al. (1992) J Invest Dermatol 99:565-571; Punnonen et al. (1993) J Invest Dermatol 101:719-726). Indeed, blocking PKC.alpha. activity or its synthesis by antisense oligonucleotides appeared to abolished granular markers and revive spinous markers like K1 and K10. Likewise, implementation of dominant negative PKC.alpha. appeared to restore the (late) spinous marker involucrin (Deucher et al. (2002) J Biol Chem 277:17032-17040). Accordingly, defective differentiation in skin cancer (Tennenbaum et al. (1993) Cancer Res 3:4803-4810; Tomakidi et al. (2003) J Pathol 200:298-307) correlates with elevated PKC.alpha. activity, also observed in tumor cells in vitro (Dlugosz et al. (1992) Biomed Pharmacother 46:304; Yang et al. (2003) J Cell Physiol. 195:249-259). However, over-expression of PKC.alpha. in normal human keratinocytes did not appear to alter their differentiation pattern (Deucher et al. (2002) J Biol Chem 277:17032-17040). The influence of PKC.alpha. on the cellular traffic and membrane recruitment of .beta.1-integrin during migration (Ng et al. (1999) EMBO J. 18:3909-3923) may well promote both wound reepithelialization and tumor cell invasion.

"Over-expression of PKC.alpha. in transgenic mice has appeared to induce a striking inflammatory response, increased epidermal thickening and edema correlated with neutrophil infiltration, multiple micro-abscesses, and a marked increase of inflammatory cytokines and chemokines, such as TNF.alpha., macrophage inflammatory protein-2 (MIP-2), Cyclooxygenase-2 (COX-2) or macrophage inflammatory protein (MIP). These results implicate PKC.alpha. in the epidermal inflammatory response (Wang and Smart (1999) J Cell Sci 112:3497-3506). Treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA, a PKC.alpha. activator) apparently caused epidermal hyperplasia, intra-epidermal inflammation, and massive apoptosis (Cataisson et al. (2003) J Immunol 171:2703-2713; Jansen et al. (2001) Int J Cancer 93:635-643). In addition, recent in vivo studies in PKC isoenzyme-selective knockout and transgenic mice appear to have highlighted distinct functions of individual PKCs in the immune system. These genetic analyses, along with biochemical studies appear to indicate that PKC-regulated signaling pathways play a significant role in many aspects of the immune responses. For example, members of the PKC family appear crucial in T cell signaling pathways. Particularly, PKC.alpha., isotype appears to determine the nature of lymphocyte-specific in vivo effector. PKC.alpha. is also discussed as being involved in macrophages activation and was apparently shown to be involved in mast cell signaling (Cataisson et al. (2005) J Immunol 174:1686-1692).

"One example of an inflammatory disease is psoriasis. There are two main hypotheses about the basic pathology leading to psoriasis development. The first considers psoriasis as primarily a disorder of excessive growth and reproduction of skin cells. The second hypothesis considers psoriasis as an immune-mediated disorder in which the excessive reproduction of skin cells is secondary to factors produced by the immune system. Accordingly, most drugs for psoriasis target one component of the disease, either the hyper-proliferative state of skin cells, or the skin inflammatory response as presented in psoriasis plaques.

"Recent data support the notion that both pathways underlie the pathology of the diseases through a cross talk between skin cells and immunological milieu (encompassing environment, surroundings, location and/or setting). Classic genome wide linkage analysis has identified nine locations (loci) on different chromosomes associated with tendency to develop psoriasis named psoriasis susceptibility 1 through 9 (PSORS1 through PSORS9) loci. In these locations several genes were characterized and found to encode for proteins expressed in epidermal cells such as corneodesmosin, expressed in the granular and cornified layers of the epidermis and upregulated in psoriasis. On the other hand, other psoriasis linked genes encode for proteins involved in modulation of the immune system where characterized such as IL-12B on chromosome 5q (Frank et al. (2009) N Engl J Med 361:496-509).

"WO 2005/007072 of some of the inventors of the present application discloses pharmaceutical compositions for topical administration, for inducing or accelerating a healing process of a damaged skin or skin wound, comprising insulin and additional agent, such as alpha PKC inhibitor, acting in synergy with the insulin.

"WO 2009/016629 of some of the inventors of the present application discloses compositions comprising a delta-PKC activator, an alpha PKC inhibitor, and a carrier that is free of calcium (Ca.sup.2+) and magnesium (Mg.sup.2+) cations for decreasing inflammation at the site of a skin wound.

"Current therapies for combating inflammatory diseases generally fail to provide a multi-component approach targeting multiple components of pathogenesis. For example, many treatments for autoimmune diseases involve targeting a single component of a disease, either by blocking cellular proliferation, or by suppressing the immune response in order to block inflammation. Consequently, there is a strong need to provide effective therapeutics which target multiple components of inflammatory disease pathogenesis by targeting and modulating PKC isoform activity. Specifically targeted therapeutics that are capable of selective inhibition or activation of specific PKC isoforms are necessary and would provide for a therapeutic approach that targets multiple components of inflammatory disease pathogenesis, while retaining a low level of side effects, for example, when topically administered. Thus, development of therapeutics that reduce secretion of proinflammatory cytokines and/or regulate immunomodulators via PKC isoform modulation would be beneficial in alleviating topical and systemic inflammation generally and specifically, inflammation of the skin and other epithelial tissues."

In addition to obtaining background information on this patent, NewsRx editors also obtained the inventors' summary information for this patent: "The present disclosure relates to treatment of inflammatory diseases and disorders by administering to a subject a modulator of PKC, such as an inhibitor of PKC.alpha., PKC.epsilon., or PKC.eta., or an activator of PKC.delta.. Specifically, the compositions and methods of the present invention are useful for the treatment of inflammatory disorders and diseases the skin and other epithelial tissues. In particular it is shown that specific peptide or polypeptide modulators of PKC isoforms are capable, not only of promoting wound healing but also to treat skin and other epithelial tissue diseases and disorders. According to some embodiments the compositions are unexpectedly effective when applied topically as a sole active ingredient.

"Without wishing to be bound by any specific theory, it is suggested that the peptide modulators of PKC according to the present invention, even when applied topically, have not only local effect on the skin cells, but also systemic effect on the immune system, leading to inhibition of the pro-inflammatory cytokine cascade.

"As exemplified herein, the modulatory peptides of the present disclosure exhibit direct effects on secretion of cytokines by splenocytes. The direct effects of the modulatory peptides are also significant on keratinocytes.

"Accordingly, in one aspect, the present disclosure provides a method of inhibiting the secretion of a pro-inflammatory cytokine in a subject suffering from an inflammatory disease or disorder, comprising administering a pharmaceutical composition comprising at least one PKC modulator peptide, thereby treating the inflammatory disease or disorder. More specifically, inflammatory diseases or disorders of the skin or other epithelial tissue are treated by administering to the subject a modulator of PKC.

"According to some embodiments, the PKC modulator is an inhibitor of certain PKC isoforms. According to some embodiments, the PKC inhibitor selectively inhibits PKC.alpha., PKC.epsilon. or PKC.eta.. According to some particular embodiments, the PKC inhibitor is a peptide according to any one of SEQ ID NOs: 1-5, 6-11, and 12-13 which selectively inhibits PKC.alpha., PKC.epsilon. and PKC.eta., respectively, or a salt, analog or derivative thereof.

"According to some embodiments, the PKC modulator is an activator of other PKC isoforms. According to some embodiments, the PKC activator selectively activates PKC. In various embodiments, the activator is a peptide of according to any one of SEQ ID NOs: 14-17, or a salt, analog or derivative thereof.

"According to some specific embodiments, a PKC modulator used in the methods of the present invention is an inhibitor of PKC alpha or epsilon selected from the group consisting of: AIP-1 (SEQ ID NO: 3), AIP-2 (SEQ ID NO: 4), EPIP-1 (SEQ ID NO: 6), EPIP-2 (SEQ ID NO: 7), EPIP-3 (SEQ ID NO: 8), EPIP-4 (SEQ ID NO: 9), EPIP-5 (SEQ ID NO: 10), EPIP-6 (SEQ ID NO: 11), or an analog, salt or derivative thereof; or an activator of PKC delta selected from the group consisting of DAP-1 (SEQ ID NO: 16), DAP-2 (SEQ ID NO: 14), DAP-3 (SEQ ID NO: 15), DAP-4 (SEQ ID NO: 17), ZIP-1 (SEQ ID NO: 18), or an analog, salt or derivative thereof. Each possibility is a preferred embodiment of the present invention.

"According to yet other embodiments, the PKC modulator used in the methods of the present invention is: i. an inhibitor of PKC alpha or epsilon selected from the group consisting of AIP-1 (SEQ ID NO: 3), AIP-2 (SEQ ID NO: 4), EPIP-1 (SEQ ID NO: 6), EPIP-2 (SEQ ID NO: 7), EPIP-3 (SEQ ID NO: 8), EPIP-4 (SEQ ID NO: 9), or an analog, salt or derivative thereof or an activator of PKC delta selected from the group consisting of: DAP-1 (SEQ ID NO: 16), DAP-2 (SEQ ID NO: 14), DAP-3 (SEQ ID NO: 15), ZIP-1 (SEQ ID NO: 18), or an analog, salt or derivative thereof. Each possibility is a preferred embodiment of the present invention.

"According to some embodiments, derivatives of the PKC modulator peptides are provided, comprising a permeability moiety conjugated to the peptide sequence.

"According to some embodiments, the permeability moiety is connected, by a covalent bond, to the N-terminus of the peptide.

"According to some embodiments the permeability moiety attached to the PKC modulator peptide is selected from the group consisting of i. hydrophobic moiety such as fatty acid, steroid and bulky aromatic or aliphatic compound; ii. moiety which may have cell-membrane receptors or carriers, such as steroid, vitamin and sugar; and iii. transporter peptide or amino acid.

"According to some embodiments, the fatty acid comprises an aliphatic tail of 3-12 carbons. According to some particular embodiments, the fatty acid is selected from the group consisting of: myristic acid, palmitic acid and cholesterol.

"According to some particular embodiments, the PKC modulator, comprising a permeability moiety is a peptide according to any one of SEQ ID NOs: 19-25, or an analog, derivative or salt thereof.

"According to some embodiments, peptides analogs, comprising modified amino- or carboxy-terminus of the PKC modulator peptide, are provided. According to some particular embodiments, the modification is selected from the group consisting of: N-terminus acylation, C-terminus amidation and modification of the C-terminal acid to an alcohol.

"According to some embodiments, the inflammatory disease of the skin is selected from the group consisting of: pruritus, skin inflammation, psoriasis, atopic dermatitis, allergic contact dermatitis, irritant contact dermatitis, and seborrhoeic dermatitis.

"According to a particular embodiment, the inflammatory disease of the skin is pruritus.

"According to yet other embodiments, the inflammatory disease or disorder of epithelial tissue is selected from the group consisting of: keratinopathy, asthma, inflammatory bowel disease such as ulcerative colitis and Crohn's disease.

"A pharmaceutical composition according to the present invention, comprising at least one PKC mediator, and a carrier, diluent or excipient, may be, according to some embodiments, free of calcium (Ca.sup.2+) and magnesium (Mg.sup.2+) cations. According to yet other embodiment, a pharmaceutical composition according to the present invention may comprise calcium (Ca.sup.2+) and/or magnesium (Mg.sup.2+) cations.

"A pharmaceutical composition comprising a PKC modulator according to the present invention may be administered by any suitable route of administration, including topically or systemically. Modes of administration include but are not limited to topical and transdermal routes as well as parenteral routes such as intravenous and intramuscular injections, as well as via nasal or oral ingestion.

"According to some embodiments, the PKC modulator is administered topically. According to other embodiments, the PKC modulator is administered systemically.

"As it is known to those skilled in the art a pharmaceutical composition comprising a PKC modulator according to the present invention may be administered alone or in conjunction with additional treatments for the conditions to be treated.

"In various aspects, the present disclosure provides a kit for carrying out the method of the disclosure. In one embodiment, the kit includes an inhibitor of PKC, such as an inhibitor of PKC.alpha., PKC.epsilon. or PKC.eta., or an activator of PKC.delta., as well as instructions for administering the inhibitor or activator.

"Some of the specific peptide modulators of PKC isoformes used in the methods of the present invention are listed in Table 1:

"TABLE-US-00001 TABLE 1 Examples of PKC Isoform Inhibitor and Activator Peptides Name Amino Acid Sequence SEQ ID PKC.alpha. Inhibitors Phe-Ala-Arg-Lys-Gly-Ala 1 Phe-Ala-Arg-Lys-Gly-Ala-Arg-Gln 2 Palmitoyl-Phe-Ala-Arg-Lys-Gly-Ala-Arg-Gln 19 AIP-1 Thr-Leu-Asn-Pro-Gln-Trp-Glu-Ser 3 Phe-Ala-Arg-Lys-Gly-Ala-Leu 4 AIP-2 Myristoyl-Phe-Ala-Arg-Lys-Gly-Ala-Leu 20 MPDY-1 Myristoyl-Phe-Ala-Arg-Lys-Gly-Ala-Leu-Arg-Gln 21 AWOT Phe-Ala-Arg-Lys-Gly-Ala-Leu-Arg-Gln 5 PPDY-1 Palmitoyl-Phe-Ala-Arg-Lys-Gly-Ala-Leu-Arg-Gln 22 PKC.epsilon. Inhibitors EPIP-1 Glu-Ala-Val-Ser-Leu-Lys-Pro-Thr 6 EPIP-2 Pro-Tyr-Ile-Ala-Leu-Asn-Val-Asp 7 EPIP-3 Pro-Ala-Trp-His-Asp 8 EPIP-4 Leu-Glu-Pro-Glu-Ala-Ala-Ala-Ala-Ala-Ala-Gly-Lys 9 EPIP-5 His-Phe-Glu-Asp-Trp-Ile-Asp 10 EPIP-6 Val-Tyr-Val-Ile-Ile-Asp-Leu 11 PKC.eta. Inhibitors Lys-Arg-Thr-Leu-Arg 12 Myristoyl-Lys-Arg-Thr-Leu-Arg 23 Thr-Arg-Lys-Arg-Gln-Arg-Ala-Met-Arg-Arg-Arg-Val-His-Gln-Ile-Asn-Gly 13 MPE-1 Myristoyl-Thr-Arg-Lys-Arg-Gln-Arg-Ala-Met-Arg-Arg-Arg-Val-His-Gln-Il- e-Asn-Gly 24 PKC.delta. Activators DAP-2 His-Phe-Glu-Asp-Thr-Ile-Asp 14 DAP-3 His-Phe-Glu-Asp-Trp-Ile-Asp-His-Phe-Glu-Asp-Trp-Ile-Asp 15 DAP-1 Met-Arg-Ala-Ala-Glu-Ala-Ala-Ala-Ala-Glu-Pro-Met 16 DAP-4 Val-Tyr-Val-Ile-Ile-Asp-Leu-His-Phe-Glu-Asp-Trp-Ile-Asp 17 PKC.zeta. Inhibitor Ser-Ile-Tyr-Arg-Arg-Gly-Ala-Arg-Arg-Trp-Arg-Lys-Leu 18 ZIP-1 Myristoyl-Ser-Ile-Tyr-Arg-Arg-Gly-Ala-Arg-Arg-Trp-Arg-Lys-Leu 25

"In another aspect, the present disclosure provides an isolated peptide modulator of PKC.

"According to some embodiments, the peptide modulator of PKC is set forth in a sequence selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 15, SEQ ID NO: 16 and SEQ ID NO: 17 or an analog, derivative or salt thereof. Each possibility represents a separate embodiment of the present invention.

"According to some embodiments, the peptide modulator of PKC is a peptide of 6-30 amino acids comprising the sequence Glu-Ala-Ala-Ala-Ala (SEQ ID NO:26). According to some specific embodiments, the peptide modulator is set forth in a sequence selected from the group consisting of SEQ ID NO: 9 and SEQ ID NO: 16, or an analog, derivative or salt thereof. Each possibility represents a separate embodiment of the present invention.

"According to other embodiments, the peptide modulator of PKC is a peptide multimer of 12-60 amino acids, comprising at least two, identical or different, sequences wherein at least one of the sequences is set forth in a sequence selected from the group consisting of SEQ ID NOs: 1-18. Each possibility represents a separate embodiment of the present invention.

"According to some specific embodiments, the peptide multimer comprises the sequence His-Phe-Glu-Asp-Trp-Ile-Asp (SEQ ID NO: 14). According to particular embodiments, the peptide multimer is set forth in a sequence selected from SEQ ID NO: 15 and SEQ ID NO:17. Each possibility represents a separate embodiment of the present invention.

"According to some embodiments the peptide modulator or peptide multimer comprises a permeability moiety. According to particular embodiments, the permeability moiety is a fatty acid. According to some specific embodiments an N-myristoylated peptide of any one of SEQ ID NOs: 9, 15, 16 and 17 is provided. Each possibility represents a separate embodiment of the present invention.

"The present disclosure further provides a pharmaceutical composition comprising at least one isolated peptide modulator of PKC and a pharmaceutically acceptable vehicle, diluent or excipient. According to some embodiments, the peptide modulator is a peptide of SEQ ID NO: 9, 15, 16 or 17, or an analog, derivative or salt thereof. According to some particular embodiments, the pharmaceutical composition comprises a peptide multimer comprising at least two, identical or different, sequences wherein at least one of the sequences is set forth in a sequence selected from the group consisting of SEQ ID NOs: 1-18. According to specific embodiments, the pharmaceutical compositions comprises a peptide multimer according to SEQ ID NO: 15 and SEQ ID NO:17. According to some specific embodiments, the pharmaceutical compositions comprise an N-myristoylated-derivative of a peptide of any one of SEQ ID NO: 9, 15, 16 and 17; and a pharmaceutically acceptable vehicle, diluent or excipient.

"In another aspect, the present invention provides a method of treating an inflammatory disease or disorder comprising administering to a subject in need thereof, a pharmaceutical composition comprising at least one peptide set forth in a sequence selected from the group consisting of: SEQ ID NO: 9, SEQ ID NO: 15, SEQ ID NO: 16 and SEQ ID NO: 17, or a peptide multimer comprising at least two, identical or different, sequences wherein at least one of the sequences is set forth in a sequence selected from the group consisting of SEQ ID NOs: 1-18 or a salt, derivative or analog thereof."

For more information, see this patent: Braiman-Wiksman, Liora; Tennenbaum, Tamar; Sagiv, Yuvai; Gartsbein, Marina; Brener, Ephraim; Ben-Hamo, Moshe; Hammer, Liat. Method for Treatment of Inflammatory Disease and Disorder. U.S. Patent Number 8349793, filed July 13, 2011, and issued January 8, 2013. Patent URL: http://patft.uspto.gov/netacgi/nph-Parser'Sect1=PTO2&Sect2=HITOFF&p=74&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=3692&f=G&l=50&co1=AND&d=PTXT&s1=20130108.PD.&OS=ISD/20130108&RS=ISD/20130108

Keywords for this news article include: Blood, Asthma, Cations, Genetics, Oncology, Allergies, Cytokines, Magnesium, Psoriasis, Dermatitis, Immunology, Leukocytes, Proteomics, Amino Acids, Dermatology, Heal0r Ltd., Macrophages, Pulmonology, Granulocytes, Inflammation, Light Metals, Therapeutics, Myeloid Cells, Allergy Medicine, Bone Marrow Cells.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2013, NewsRx LLC