Anti-inflammatory peptides and uses thereof

Abstract

To provide anti-inflammatory drugs that are not immune suppressive and / or would not cause other adverse side effects.SOLUTION: The anti-inflammatory peptide comprises an anti-inflammatory fragment of a protein of specific sequence, where the fragment is from 7 to 37 amino acids in length, having a charge of from -9 to +3, whose C terminal amino acid is neither cysteine nor methionine, whose N terminal amino acid is neither cysteine, histidine, proline nor threonine. The anti-inflammatory fragment has no cysteine. The anti-inflammatory fragment is derived from a region of a protein of specific amino acid sequence, and the region is from 17 to 109 amino acids in length and has a charge of between -6 and +4, the C terminal amino acid of the region is neither aspartic acid, phenyl alanine, methionine nor tryptophan, and the N terminal amino acid of the region is neither aspartic acid, histidine, methionine, proline nor tryptophan.SELECTED DRAWING: None

Description

[Background technology]

[0001] It is estimated that as many as two billion people worldwide suffer from some type of inflammation. Inflammation is a vast biological process and an integral part of our immune response. Inflammatory responses can be acute (short-lasting) or chronic (longer-lasting) and can occur in almost any part of the body, whether internal or external. Interestingly, the biological changes that occur in the body due to the inflammatory response are similarly the same throughout the body, regardless of the cause of the inflammation, meaning that different anti-inflammatory agents reduce inflammation in the same way in all parts of the body.

[0002] Normally, inflammation is a natural response, necessary to remove damaging cells, attack foreign bodies, or remove dead cells. However, excessive inflammation can have dramatic, sometimes harmful, effects on the human body. In fact, inflammatory responses can have negative consequences, such as persistent tissue damage. During an inflammatory response, the body releases lysosomal enzymes that can damage tissue and further lead to life-threatening hypersensitivity reactions. These conditions can have persistent effects externally, with the development of acute rashes and eczema, and internally, by inducing diseases such as inflammatory bowel disease. As a result, maintaining normal levels of inflammation is crucial for both our internal and external health and well-being. Unfortunately, inflammation is on the rise. One of the major factors behind this increase is our body's increased exposure to a variety of external agents to which it is unaccustomed.

[0003] Most anti-inflammatory treatments used today are drugs. There are two major types of anti-inflammatory drugs: corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). These include immunosuppressants (methotrexate, cyclosporine); specific biologics (primarily TNF-α inhibitors, but also, for example, inhibitors of the cyclooxygenase enzyme); cytotoxic agents and oral retinoids (acitretin). In addition, topical treatments exist to specifically reduce skin inflammation. Examples include creams and ointments (primarily cortisone-based) and physical treatments such as UV irradiation. However, these drugs have severe side effects, such as gastrointestinal toxicity and anaphylactoid reactions. They can also suppress the immune system to the point of making it vulnerable to other diseases and pathogens.

[0004] Therefore, there is a clear need to identify agents with anti-inflammatory activity that are not immunosuppressive and / or do not cause other undesirable side effects. To that end, very specific types of foods have been found to reduce inflammation (Non-Patent Document 1, Non-Patent Document 2, Non-Patent Document 3). Indeed, the specific components of these specific foods are in low concentrations, hidden, or confined, but once identified and brought to light, our bodies understand the food components and can easily process these molecules, so they can be tailored to specifically target inflammation in a recognized manner. In fact, these specific food molecules may completely shut off this immune system response and reduce inflammation without leaving the body in a vulnerable state. Similarly, for those with multiple food allergies, identifying and bringing to light specific components of foods that can reduce inflammation could allow these individuals to benefit from the anti-inflammatory properties of foods to which they would otherwise be allergic. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] US Patent Application Publication No. 2014120131 [Patent Document 2] US Patent Application Publication No. 2004132667 [Patent Document 3] U.S. Patent No. 4,186,183 [Patent Document 4] U.S. Patent No. 4,217,344 [Patent Document 5] U.S. Patent No. 4,235,871 [Patent Document 6] U.S. Patent No. 4,261,975 [Patent Document 7] U.S. Patent No. 4,485,054 [Patent Document 8] U.S. Patent No. 4,501,728 [Patent Document 9] U.S. Patent No. 4,774,085 [Patent Document 10] U.S. Patent No. 4,837,028 [Patent Document 11] U.S. Patent No. 4,946,787 [Patent Document 12] PCT Publication Number International Publication No. 91 / 17424 Pamphlet [Patent Document 13] European Patent No. 2050437 [Patent Document 14] International Publication No. 2005023290 Brochure [Patent Document 15] US Patent Application Publication No. 2010098660 [Patent Document 16] US Patent Application Publication No. 20070053845 [Patent Document 17] European Patent No. 1072600.2 [Patent Document 18] European Patent No. 13171757.1 [Patent Document 19] US Patent Application Publication No. 2014120141 [Non-patent literature]

[0006] [Non-licensed document 1] Kiecolt-Glaser JK et al. 2010 [Non-licensed document 2] Middleton E. et al. 2000 [Non-licensed document 3] Chatterjee M. et al. 2005

Non-licensed Document 4

Non-licensed Document 5

Non-licensed Document 6

Non-licensed Document 7

Non-licensed literature 9

Non-licensed literature 10

Non-licensed Document 11

Non-licensed Document 12

Non-licensed Document 13

[0007] It is an object of the present invention to overcome at least one of the above problems. [Means for solving the problem]

[0008] Description of the Invention The pea genome encodes over 70,000 different proteins. Applicants have identified seven of these proteins, each of which contains one or more anti-inflammatory fragments. Similarly, of the over 60,000 proteins encoded by the rice genome, Applicants have identified eight proteins, each of which contains one or more anti-inflammatory fragments. Anti-inflammatory fragments of the 16 identified proteins have anti-inflammatory activity when incubated with human cells stimulated with LPS (Figures 1 to 19), do not cause human cell viability problems (Figure 20), and are not toxic to human cells (Figure 21). Specific plant proteins from which natural peptides are derived are provided in SEQ ID NOS: 1-15 and 353-355, particularly from regions of the proteins provided in SEQ ID NOS: 17-69. Specific pea proteins from which peptides are derived are provided in SEQ ID NOS: 1-5, 8, and 9, and specific rice proteins from which peptides are derived are provided in SEQ ID NOS: 6, 7, and 10-15.

[0009] Homologs of these proteins are set forth in SEQ ID NOS: 222-267. Specific peptides first identified in pea proteins are set forth in SEQ ID NOS: 71-107 and 110-111. Specific peptides first identified in rice proteins are set forth in SEQ ID NOS: 108-109 and 112-220. Additional peptides of the invention identified in pea and rice proteins are provided herein, for example, in SEQ ID NOS: 320, 331-352 and 356-424. Peptides of the invention include peptides comprising or consisting of any of the above peptides.

[0010] EWQINEK (SEQ ID NO: 331) - a fragment of the rice protein of SEQ ID NO: 7 FLPQHTD (SEQ ID NO: 332) - fragment of the pea protein of SEQ ID NO: 1 GPQQYAEWQINEK (SEQ ID NO: 333) - a fragment of the rice protein of SEQ ID NO: 7 PGQLQSFLLSGN (SEQ ID NO: 334) - fragment of the pea protein of SEQ ID NO: 1 PGQLQSFLLSGNQNQQNYLSGF (SEQ ID NO: 335) - fragment of the pea protein of SEQ ID NO: 1 PQQYAEWQ (SEQ ID NO: 336) - Fragment of the rice protein of SEQ ID NO: 7 QLQSFLLSGNQNQQNYLSGFSK (SEQ ID NO: 337) - a fragment of the pea protein of SEQ ID NO: 1 QNQQNYLSGFSK (SEQ ID NO: 338) - a fragment of the pea protein of SEQ ID NO: 1 QSFLLSGNQNQQ (SEQ ID NO: 339) - fragment of the pea protein of SEQ ID NO: 1 QSFLLSGNQ (SEQ ID NO: 340) - fragment of the pea protein of SEQ ID NO: 1 RGPQQYA (SEQ ID NO: 341) - a fragment of the rice protein of SEQ ID NO: 7 DALEPDNR (SEQ ID NO: 342) - a fragment of the pea protein of SEQ ID NO: 354 SEEGYYGEQQQQPGMTR (SEQ ID NO: 343) - Fragment of the rice protein of SEQ ID NO: 353 GYYGEQQQQPGMTR() - Fragment of rice protein of SEQ ID NO: 353 IDGYDTPVEGR (SEQ ID NO: 345) - a fragment of the rice protein of SEQ ID NO: 15 NGVLRPGQL (SEQ ID NO: 346) - a fragment of the rice protein of SEQ ID NO: 14 RHGEWGPSY (SEQ ID NO: 347) FWM (SEQ ID NO: 348) - a fragment of the pea protein of SEQ ID NO: 3 TVFDGVLRPGQL [SEQ ID NO: 349] - fragment of the rice protein of SEQ ID NO: 10 RLQSQNDQRGEIIHVK [SEQ ID NO: 350] - fragment of the rice protein of SEQ ID NO: 10 HGPVEMPYTLLYPSSK [SEQ ID NO: 351] - a fragment of the pea protein of SEQ ID NO: 355 LDALEPDNR [SEQ ID NO: 352] - a fragment of the pea protein of SEQ ID NO: 354 RGPQQYAEWQINE [SEQ ID NO: 320] - Fragment of the rice protein of SEQ ID NO: 7

[0011] The peptides of the present invention are primarily useful for causing a reduction in inflammation and therefore have utility in the prevention or treatment of inflammatory conditions and the maintenance of intestinal health in mammals.

[0012] In a first aspect, the present invention provides a peptide, or a variant or fragment of the peptide (hereinafter "peptide of the invention"), comprising a fragment of a protein or homolog thereof disclosed herein, e.g., selected from SEQ ID NOs: 1 to 16, 349 or 350, typically 3 to 50 amino acids in length. In one embodiment, the peptide or variant or fragment thereof is biologically active. In one embodiment, the peptide or variant or fragment thereof has anti-inflammatory activity.

[0013] In one embodiment, the peptide of the present invention comprises a sequence selected from SEQ ID NOs: 17-220, 268-352 and 356-424.

[0014] In one embodiment, the peptide of the present invention consists essentially of a sequence selected from SEQ ID NOs: 17-220, 268-352 and 356-424.

[0015] In one embodiment, the peptide consists of 3 to 50 amino acids. In one embodiment, the peptide consists of 4 to 50 amino acids. In one embodiment, the peptide consists of 5 to 50 amino acids. In one embodiment, the peptide consists of 6 to 50 amino acids.

[0016] In one embodiment, the fragment has between 7 and 37 amino acids and a charge between -9 and +3.

[0017] Preferably, the C-terminal amino acid is not cysteine ​​(C) or methionine (M).

[0018] Preferably, the N-terminal amino acid is not cysteine ​​(C), histidine (H), proline (P) or threonine (T).

[0019] Preferably, the C-terminal domain of the fragment does not contain a cysteine ​​(C).

[0020] Preferably, the N-terminal domain of the fragment does not contain a cysteine ​​(C).

[0021] Preferably, the fragment does not contain a cysteine ​​(C).

[0022] Preferably, the peptide does not contain a cysteine ​​(C).

[0023] Preferably, the fragment is derived from a region of the protein of SEQ ID NO: 1 to 16, which region is characterized by the following features: - 17 to 109 amino acids in length, - charge between -6 and +4, - the C-terminal amino acid is not aspartic acid (D), phenylalanine (F), methionine (M) or tryptophan (W); - The N-terminal amino acid is not aspartic acid (D), histidine (H), methionine (M), proline (P), or tryptophan (W).

[0024] Preferably, the C-terminal domain of the region does not contain a tryptophan (W).

[0025] Preferably, the regions of the proteins of SEQ ID NOs: 1 to 7 are selected from SEQ ID NOs: 17-33.

[0026] Preferably, the regions of the proteins of SEQ ID NOs: 8 to 16 are selected from SEQ ID NOs: 34-70.

[0027] Preferably, the region of the protein of SEQ ID NO: 1 to 16 is selected from SEQ ID NO: 17-70.

[0028] Preferably, the fragment is selected from SEQ ID NOs: 71 to 221 or a variant of the fragment.

[0029] Preferably, the peptide consists of a fragment or variant of a fragment selected from SEQ ID NOs: 71 to 221.

[0030] Preferably, the peptide consists of a sequence selected from SEQ ID NOs: 71 to 221.

[0031] In one embodiment the peptide comprises a fragment of a pea protein, wherein the fragment is selected from SEQ ID NOs: 71-107, 332, 334, 335, 337-340, 342, 348 and 351-352.

[0032] In one embodiment the peptide comprises a fragment of a pea protein, wherein the fragment is selected from SEQ ID NOs: 71-107, 332, 334, 335, 337-340, 342, 348 and 351-352. In one embodiment the fragment is selected from 339, 352, 351, 93, 92, 75, 76, 105.

[0033] In one embodiment, the peptide comprises a fragment of a rice protein, wherein the fragment is selected from SEQ ID NOs: 108-109, 112-220, 320, 331, 333, 336, 341, 343-346, 349-350. In one embodiment, the fragment is selected from 341, 144, 320, 349, 350, 177, 343-346.

[0034] In one embodiment, the peptide is a modified peptide. In one embodiment, the peptide is modified with a protecting group. In one embodiment, the peptide is modified to increase its lipophilicity. In one embodiment, the peptide is modified to increase its half-life. In one embodiment, the N- or C-terminal amino acid of the peptide is modified. In one embodiment, the N- or C-terminal amino acid of the peptide is modified with a protecting group.

[0035] The present invention also provides a conjugate comprising a peptide of the present invention conjugated to a binding partner, hi one embodiment, the peptide of the present invention is modified with a reactive group configured to allow conjugation to a binding partner.

[0036] [SEQ ID NO: 1 (pea protein 1)] Preferably, the peptide comprises a biologically active fragment of the protein of SEQ ID NO: 1 or a homologue thereof, or a biologically active variant of that protein fragment.

[0037] Preferably, the peptide comprises seven regions of SEQ ID NO: 1, ie a biologically active fragment of one of SEQ ID NOs: 17 to 23, or a biologically active variant of that protein fragment.

[0038] Preferably, the peptide comprises a biologically active fragment selected from SEQ ID NOs: 71 to 91 or 360, or a biologically active variant of that protein fragment.

[0039] Preferably, the peptide comprises a fragment of a region of SEQ ID NO: 17, for example SEQ ID NO: 71, or a biologically active variant of that protein fragment.

[0040] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 18, for example SEQ ID NO: 72, or a biologically active variant of the fragment.

[0041] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 19, for example, either or both of SEQ ID NOs: 73 or 74, or a biologically active variant of the fragment.

[0042] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 20, for example, either or both of SEQ ID NO: 75 or 76, or a biologically active variant of the fragment.

[0043] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 21, for example one or more or all of SEQ ID NOs: 77 to 84, or a biologically active variant of that fragment.

[0044] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 22, for example one or more or all of SEQ ID NOs: 85 to 89, or a biologically active variant of that fragment.

[0045] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 23, for example SEQ ID NO: 90, or a biologically active variant of that fragment.

[0046] Preferably, the peptide comprises SEQ ID NO: 91, or a biologically active variant of a fragment thereof.

[0047] The present invention also provides a composition comprising at least one peptide of the present invention, wherein the peptide comprises a fragment of SEQ ID NO: 1 or a homolog thereof. The present invention also provides a composition comprising at least two, preferably three, preferably four, preferably five, preferably six, preferably seven, preferably eight, preferably nine, or preferably ten, peptides of the present invention, each comprising a different fragment of SEQ ID NO: 1 or a homolog thereof. Preferably, the peptide(s) are biologically active. Preferably, the peptide(s) are anti-inflammatory. Preferably, the composition comprises a first peptide of the present invention comprising a fragment of a first region selected from SEQ ID NOs: 17 to 23 and a second peptide of the present invention comprising a fragment of a second region selected from SEQ ID NOs: 17 to 23. Preferably, the composition comprises a first biologically active peptide comprising a first biologically active fragment (or a biologically active variant of the fragment) selected from SEQ ID NOs: 71 to 91 and a second biologically active peptide comprising a second biologically active fragment (or a biologically active variant of the fragment) selected from SEQ ID NOs: 71 to 91.

[0048] Homologues of pea protein 1 (SEQ ID NO: 1) include broad bean (Vicia fabia), chickpea (Cicer arietinum) and lentil (Lens culinaris) homologues (SEQ ID NOs: 222-224).

[0049] [SEQ ID NO: 2 (pea protein 2)] Preferably, the peptide comprises a biologically active fragment of the protein of SEQ ID NO: 2 or a homologue thereof.

[0050] Preferably, the peptide comprises a biologically active fragment of one of two regions of SEQ ID NO:2, namely SEQ ID NO:24 or SEQ ID NO:25.

[0051] Preferably, the peptide comprises a region of SEQ ID NO: 24, for example a biologically active fragment of SEQ ID NO: 92, or a biologically active variant of that fragment.

[0052] Preferably, the peptide comprises a region of SEQ ID NO: 25, for example a biologically active fragment of SEQ ID NO: 93, or a biologically active variant of that fragment.

[0053] The present invention also provides compositions comprising at least one bioactive peptide of the present invention, wherein the peptide comprises a bioactive fragment of SEQ ID NO:2 or a homolog thereof. The present invention also provides compositions comprising at least two bioactive peptides of the present invention, each comprising a different bioactive fragment of SEQ ID NO:2 or a homolog thereof. Preferably, the composition comprises a first bioactive peptide comprising a bioactive fragment of the region of SEQ ID NO:24 and a second bioactive peptide comprising a bioactive fragment of the region of SEQ ID NO:25. Preferably, the composition comprises a first bioactive peptide comprising a bioactive fragment of SEQ ID NO:92 and a second bioactive peptide comprising a bioactive fragment of SEQ ID NO:93.

[0054] Homologues of pea protein 2 (SEQ ID NO: 2) include lentil, Vicia narbonensis, and soybean (Glycine max) (SEQ ID NOs: 225-227).

[0055] [SEQ ID NO: 3 (pea protein 3)] Preferably, the peptide comprises a biologically active fragment of the protein of SEQ ID NO: 3 or a homologue thereof.

[0056] Preferably, the peptide comprises a biologically active fragment of one of two regions of SEQ ID NO:3, namely SEQ ID NO:26 or SEQ ID NO:27.

[0057] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 26, for example SEQ ID NO: 94, or a biologically active variant of that fragment.

[0058] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 27, for example SEQ ID NO: 95, or a biologically active variant of that fragment.

[0059] The present invention also provides a composition comprising at least a bioactive peptide of the present invention, wherein the peptide comprises a bioactive fragment of SEQ ID NO:3 or a homolog thereof. The present invention also provides a composition comprising at least two bioactive peptides of the present invention, each comprising a different bioactive fragment of SEQ ID NO:3 or a homolog thereof. Preferably, the composition comprises a first peptide comprising a bioactive fragment of a region of SEQ ID NO:26 and a second peptide comprising a bioactive fragment of SEQ ID NO:27. Preferably, the composition comprises a first bioactive peptide comprising a bioactive fragment of SEQ ID NO:94 (or a bioactive variant of the fragment) and a second bioactive peptide comprising a bioactive fragment of SEQ ID NO:95 (or a bioactive variant of the fragment).

[0060] Homologues of pea protein 3 (SEQ ID NO: 3) include Vicia sativa, Medicago truncatula and Lotus japonicas (SEQ ID NOs: 228-230).

[0061] [SEQ ID NO: 4 (pea protein 4)] Preferably, the peptide comprises a biologically active fragment of the protein of SEQ ID NO: 4 or a homologue thereof.

[0062] Preferably, the peptide comprises five regions of SEQ ID NO: 4, i.e., a biologically active fragment of one of SEQ ID NOs: 28 to 32. Preferably, the region is SEQ ID NO: 28, preferably SEQ ID NO: 29, preferably SEQ ID NO: 30, preferably SEQ ID NO: 31, preferably SEQ ID NO: 32.

[0063] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 28, for example SEQ ID NO: 96, or a biologically active variant of that fragment.

[0064] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 29, for example SEQ ID NOs: 97 to 103, or a biologically active variant of that fragment.

[0065] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 30, for example SEQ ID NO: 104, or a biologically active variant of that fragment.

[0066] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 31, for example SEQ ID NO: 105, or a biologically active variant of that fragment.

[0067] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 32, for example SEQ ID NO: 106, or a biologically active variant of that fragment.

[0068] The present invention also provides a composition comprising at least one bioactive peptide of the present invention, wherein the peptide comprises a bioactive fragment of SEQ ID NO: 4 or a homolog thereof. The present invention also provides a composition comprising at least two, preferably three, preferably four, preferably five, preferably six, preferably seven, preferably eight, preferably nine, or preferably ten, peptides of the present invention comprising different bioactive fragments of SEQ ID NO: 4 or a homolog thereof. Preferably, the composition comprises a first peptide comprising a bioactive fragment of a first region selected from SEQ ID NOs: 28-32 and a second peptide comprising a bioactive fragment of a second region selected from SEQ ID NOs: 28-32. Preferably, the composition comprises a first bioactive peptide comprising a first bioactive fragment selected from SEQ ID NOs: 96-106 (or a bioactive variant of that fragment) and a second bioactive peptide comprising a second bioactive fragment selected from SEQ ID NOs: 96-106 (or a bioactive variant of that fragment).

[0069] Homologues of pea protein 4 (SEQ ID NO: 4) include Pisum abyssinicum, Lathyrus annuus, and Vicia villosa (SEQ ID NOs: 231-233).

[0070] [SEQ ID NO: 5 (pea protein 5)] Preferably, the peptide comprises a biologically active fragment of the protein of SEQ ID NO: 5 or a homologue thereof.

[0071] Preferably, the peptide comprises a region of SEQ ID NO:5, ie, a biologically active fragment of a region of SEQ ID NO:33, for example SEQ ID NO:107, or a biologically active variant of that fragment.

[0072] The present invention also provides compositions comprising at least one biologically active peptide of the present invention, wherein the peptide comprises a biologically active fragment of SEQ ID NO: 5 or a homolog thereof. The present invention also provides compositions comprising at least two peptides of the present invention, each comprising at least one biologically active fragment of SEQ ID NO: 5 or a homolog thereof, e.g., SEQ ID NO: 107.

[0073] Homologues of pea protein 5 (SEQ ID NO: 5) include Medicago sativa, Vicia peregrine, and Vicia lutea (SEQ ID NOs: 234-236).

[0074] [SEQ ID NO: 6 (Rice Protein 7-Q6K508)] Preferably, the peptide comprises a biologically active fragment of the protein of SEQ ID NO: 6 or a homologue thereof.

[0075] Preferably, the peptide comprises a biologically active fragment of SEQ ID NO: 108 or a biologically active variant of that fragment.

[0076] The present invention also provides compositions comprising at least one biologically active peptide of the present invention, wherein the peptide comprises a biologically active fragment of SEQ ID NO: 6 or a homolog thereof. The present invention also provides compositions comprising at least two peptides of the present invention, each comprising at least one biologically active fragment of SEQ ID NO: 6 or a homolog thereof, e.g., SEQ ID NO: 108 (SP1).

[0077] Homologues of rice protein 7 (SEQ ID NO: 6) include Oryza brachyantha, Avena sativa, and Brachypodium distachyon (SEQ ID NOs: 237-239).

[0078] [SEQ ID NO: 7 (Rice protein 8-Q6K7K6)] Preferably, the peptide comprises a biologically active fragment of the protein of SEQ ID NO: 7 or a homologue thereof.

[0079] Preferably, the peptide comprises a biologically active fragment of SEQ ID NO: 109 (SP2) or a biologically active variant of that fragment.

[0080] The present invention also provides compositions comprising at least one biologically active peptide of the present invention, wherein the peptide comprises a biologically active fragment of SEQ ID NO: 7 or a homolog thereof. The present invention also provides compositions comprising at least two peptides of the present invention, each comprising at least one biologically active fragment of SEQ ID NO: 7 or a homolog thereof, e.g., SEQ ID NO: 109 (SP2).

[0081] Homologues of rice protein 8 (SEQ ID NO: 7) include those from Oryza sativa Japonica Group, Oryza sativa Indica Group, and Oryza brachyantha (SEQ ID NOs: 240-242).

[0082] [SEQ ID NO: 8 (Pea Protein 6-P13919)] Preferably, the peptide comprises a biologically active fragment of the protein of SEQ ID NO: 8 or a homologue thereof.

[0083] Preferably, the peptide comprises a biologically active fragment of SEQ ID NO: 110 (SP3) or a biologically active variant of that fragment.

[0084] The present invention also provides compositions comprising at least one biologically active peptide of the present invention, wherein the peptide comprises a biologically active fragment of SEQ ID NO: 8 or a homolog thereof. The present invention also provides compositions comprising at least two peptides of the present invention, each comprising at least one biologically active fragment of SEQ ID NO: 8 or a homolog thereof, e.g., SEQ ID NO: 110 (SP3).

[0085] Homologues of pea protein 8 (SEQ ID NO: 8) include Pisum fulvum, Pisum abyssinicum and Pisum sativum (SEQ ID NOs: 243-245).

[0086] [SEQ ID NO: 9 (Pea Protein 7-P02855)] Preferably, the peptide comprises a biologically active fragment of the protein of SEQ ID NO: 9 or a homologue thereof.

[0087] Preferably, the peptide comprises a biologically active fragment of SEQ ID NO: 111 (SP4) or a biologically active variant of that fragment.

[0088] The present invention also provides compositions comprising at least one biologically active peptide of the present invention, wherein the peptide comprises a biologically active fragment of SEQ ID NO: 9 or a homolog thereof. The present invention also provides compositions comprising at least two peptides of the present invention, each comprising at least one biologically active fragment of SEQ ID NO: 9 or a homolog thereof, e.g., SEQ ID NO: 111 (SP4).

[0089] Homologues of pea protein 9 (SEQ ID NO: 9) include Lathyrus hirsutus, Lathyrus cicero, and Lathyrus sativus (SEQ ID NOs: 246-248).

[0090] [SEQ ID NO: 10 (Rice Protein 1-P07728)] Preferably, the peptide comprises a biologically active fragment of the protein of SEQ ID NO: 10 or a homologue thereof.

[0091] Preferably, the peptide comprises nine regions of SEQ ID NO: 10, i.e., a fragment of one of SEQ ID NOs: 34 to 42. Preferably, the region is SEQ ID NO: 34, preferably SEQ ID NO: 35, preferably SEQ ID NO: 36, preferably SEQ ID NO: 37, preferably SEQ ID NO: 38, preferably SEQ ID NO: 39, preferably SEQ ID NO: 40, preferably SEQ ID NO: 41, preferably SEQ ID NO: 42.

[0092] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO:34, for example, SEQ ID NO:112 or SEQ ID NO:113, or a biologically active variant of the fragment.

[0093] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 35, for example SEQ ID NO: 114, or a biologically active variant of that fragment.

[0094] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO:36, for example, SEQ ID NO:115 or SEQ ID NO:116, or a biologically active variant of the fragment.

[0095] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO:37, for example, SEQ ID NO:117 or SEQ ID NO:118, or a biologically active variant of that fragment.

[0096] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 38, for example SEQ ID NO: 119, or a biologically active variant of that fragment.

[0097] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 39, for example SEQ ID NO: 120, 121 or 122, or a biologically active variant of that fragment.

[0098] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 40, for example SEQ ID NO: 123, or a biologically active variant of that fragment.

[0099] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 41, for example SEQ ID NO: 124, 125, 126, 127, 128 or 129, or a biologically active variant of that fragment.

[0100] Preferably, the peptide comprises a fragment of a region of SEQ ID NO: 42, for example, SEQ ID NO: 130, 131 or 132, or a biologically active variant of that fragment.

[0101] The present invention also provides a composition comprising at least one bioactive peptide of the present invention, wherein the peptide comprises a bioactive fragment of SEQ ID NO: 10 or a homolog thereof. The present invention also provides a composition comprising at least two, preferably three, preferably four, preferably five, preferably six, preferably seven, preferably eight, preferably nine, or preferably ten, peptides of the present invention, each comprising a different bioactive fragment of SEQ ID NO: 10 or a homolog thereof. Preferably, the composition comprises a first peptide comprising a bioactive fragment of a first region selected from SEQ ID NOs: 34 to 42 and a second peptide comprising a bioactive fragment of a second region selected from SEQ ID NOs: 34 to 42. Preferably, the composition comprises a first bioactive peptide comprising a first bioactive fragment selected from SEQ ID NOs: 112 to 132 (or a bioactive variant of that fragment) and a second bioactive peptide comprising a second bioactive fragment selected from SEQ ID NOs: 112 to 132 (or a bioactive variant of that fragment).

[0102] Homologues of rice protein 1 (SEQ ID NO: 10) include Oryza brachyantha and Zizania latifolia (SEQ ID NOs: 249-251).

[0103] [SEQ ID NO: 11 (Rice Protein 2-P07728)] Preferably, the peptide comprises a biologically active fragment of the protein of SEQ ID NO: 11 or a homologue thereof.

[0104] Preferably, the peptide comprises a biologically active fragment of one of four regions of SEQ ID NO: 11, namely SEQ ID NOs: 43 to 46. Preferably, the region is SEQ ID NO: 43, preferably SEQ ID NO: 44, preferably SEQ ID NO: 45, preferably SEQ ID NO: 46.

[0105] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 43, for example SEQ ID NO: 133, or a biologically active variant of that fragment.

[0106] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 44, for example SEQ ID NOs: 134 to 137, or a biologically active variant of that fragment.

[0107] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 45, for example SEQ ID NOs: 138 to 144, or a biologically active variant of that fragment.

[0108] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 46, for example SEQ ID NO: 145, or a biologically active variant of that fragment.

[0109] The present invention also provides a composition comprising at least one bioactive peptide of the present invention, wherein the peptide comprises a bioactive fragment of SEQ ID NO: 11 or a homolog thereof. The present invention also provides a composition comprising at least two, preferably three, preferably four, preferably five, preferably six, preferably seven, preferably eight, preferably nine, or preferably ten, peptides of the present invention, each of which comprises a bioactive fragment of SEQ ID NO: 11 or a homolog thereof. Preferably, the composition comprises a first peptide comprising a bioactive fragment of a first region selected from SEQ ID NOs: 43-46 and a second peptide comprising a bioactive fragment of a second region selected from SEQ ID NOs: 43-46. Preferably, the composition comprises a first bioactive peptide comprising a first bioactive fragment (or a bioactive variant of the fragment) selected from SEQ ID NOs: 133-145 and a second bioactive peptide comprising a second bioactive fragment (or a bioactive variant of the fragment) selected from SEQ ID NOs: 133-145.

[0110] Homologues of rice protein 2 (SEQ ID NO: 11) include those from rice indica, Zizania latifolia, and oats (SEQ ID NOs: 252 to 254).

[0111] [SEQ ID NO: 12 (Rice Protein 3-P07730)] Preferably, the peptide comprises a biologically active fragment of the protein of SEQ ID NO: 12 or a homologue thereof.

[0112] Preferably, the peptide comprises a biologically active fragment of one of eight regions of SEQ ID NO: 12, i.e., SEQ ID NOs: 47 to 54. Preferably, the region is SEQ ID NO: 47, preferably SEQ ID NO: 48, preferably SEQ ID NO: 49, preferably SEQ ID NO: 50, preferably SEQ ID NO: 51, preferably SEQ ID NO: 52, preferably SEQ ID NO: 53, preferably SEQ ID NO: 54.

[0113] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 47, for example, one of SEQ ID NOs: 146 to 150, or a biologically active variant of that fragment.

[0114] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 48, for example, one of SEQ ID NOs: 151 to 157, or a biologically active variant of that fragment.

[0115] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO:49, for example, one of SEQ ID NO:158 or SEQ ID NO:159, or a biologically active variant of that fragment.

[0116] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 50, for example, one of SEQ ID NOs: 160 to 162, or a biologically active variant of that fragment.

[0117] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 51, for example, one of SEQ ID NOs: 163 or 164, or a biologically active variant of that fragment.

[0118] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 52, for example SEQ ID NO: 165, or a biologically active variant of that fragment.

[0119] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 53, for example, one of SEQ ID NOs: 166 to 171, or a biologically active variant of that fragment.

[0120] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 54, for example, one of SEQ ID NOs: 172 to 176, or a biologically active variant of that fragment.

[0121] The present invention also provides a composition comprising at least one bioactive peptide of the present invention, wherein the peptide comprises a bioactive fragment of SEQ ID NO: 12 or a homolog thereof. The present invention also provides a composition comprising at least two, preferably three, preferably four, preferably five, preferably six, preferably seven, preferably eight, preferably nine, or preferably ten, peptides of the present invention, each of which comprises a bioactive fragment of SEQ ID NO: 12 or a homolog thereof. Preferably, the composition comprises a first peptide comprising a bioactive fragment of a first region selected from SEQ ID NOs: 47-54 and a second peptide comprising a bioactive fragment of a second region selected from SEQ ID NOs: 47-54. Preferably, the composition comprises a first bioactive peptide comprising a first bioactive fragment selected from SEQ ID NOs: 146-172 (or a bioactive variant of that fragment) and a second bioactive peptide comprising a second anti-inflammatory fragment selected from SEQ ID NOs: 146-172 (or a bioactive variant of that fragment).

[0122] Homologues of rice protein 3 (SEQ ID NO: 12) include Oryza brachyantha and Brachypodium indicum (SEQ ID NOs: 255-257).

[0123] [SEQ ID NO: 13 (Rice protein 4-Q0D7S0)] Preferably, the peptide comprises a biologically active fragment of the protein of SEQ ID NO: 13 or a homologue thereof.

[0124] Preferably, the peptide comprises a region of SEQ ID NO: 13, ie, SEQ ID NO: 55, a biologically active fragment of, for example, SEQ ID NO: 177, or a biologically active variant of that fragment.

[0125] The present invention also provides compositions comprising at least one biologically active peptide of the present invention, wherein the peptide comprises a biologically active fragment of SEQ ID NO: 13 or a homolog thereof. The present invention also provides compositions comprising at least two peptides of the present invention, at least one of which comprises a biologically active fragment of SEQ ID NO: 13 or a homolog thereof, e.g., SEQ ID NO: 177, or a biologically active variant of that fragment.

[0126] Homologues of rice protein 4 (SEQ ID NO: 13) include those from rice indica, Zizania latifolia, and oats (SEQ ID NOs: 252 to 254).

[0127] [SEQ ID NO: 14 (Rice Protein 5-P14614)] Preferably, the peptide comprises a fragment of the protein of SEQ ID NO: 14 or a homologue thereof.

[0128] Preferably, the peptide comprises seven regions of SEQ ID NO: 14, i.e., a biologically active fragment of one of SEQ ID NOs: 56 to 62. Preferably, the region is SEQ ID NO: 56, preferably SEQ ID NO: 57, preferably SEQ ID NO: 58, preferably SEQ ID NO: 59, preferably SEQ ID NO: 60, preferably SEQ ID NO: 61, preferably SEQ ID NO: 62.

[0129] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 56, for example, one of SEQ ID NOs: 178 to 180, or a biologically active variant of that fragment.

[0130] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 57, for example, one of SEQ ID NOs: 181-182, or a biologically active variant of that fragment.

[0131] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 58, for example SEQ ID NO: 183, or a biologically active variant of that fragment.

[0132] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 59, for example, one of SEQ ID NOs: 184 to 190, or a biologically active variant of that fragment.

[0133] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 60, for example SEQ ID NO: 191, or a biologically active variant of that fragment.

[0134] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 61, for example, one of SEQ ID NOs: 192 to 195, or a biologically active variant of that fragment.

[0135] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 62, for example, one of SEQ ID NOs: 196-197, or a biologically active variant of that fragment.

[0136] The present invention also provides a composition comprising at least one bioactive peptide of the present invention, wherein the peptide comprises a bioactive fragment of SEQ ID NO: 14 or a homolog thereof. The present invention also provides a composition comprising at least two, preferably three, preferably four, preferably five, preferably six, preferably seven, preferably eight, preferably nine, or preferably ten, peptides of the present invention, each of which comprises a bioactive fragment of SEQ ID NO: 14 or a homolog thereof. Preferably, the composition comprises a first peptide comprising a bioactive fragment of a first region selected from SEQ ID NOs: 56-62 and a second peptide comprising a bioactive fragment of a second region selected from SEQ ID NOs: 56-62. Preferably, the composition comprises a first bioactive peptide comprising a first bioactive fragment selected from SEQ ID NOs: 178-197 (or a bioactive variant of that fragment) and a second bioactive peptide comprising a second bioactive fragment selected from SEQ ID NOs: 178-197 (or a bioactive variant of that fragment).

[0137] Homologues of rice protein 5 (SEQ ID NO: 14) include Oryza japonica and Brachypodium indicum (SEQ ID NOs: 261 to 263).

[0138] [SEQ ID NO: 15 (Rice Protein 6-Q0DEV5)] Preferably, the peptide comprises a biologically active fragment of the protein of SEQ ID NO: 15 or a homologue thereof.

[0139] Preferably, the peptide comprises seven regions of SEQ ID NO: 15, i.e., a biologically active fragment of one of SEQ ID NOs: 63 to 67. Preferably, the region is SEQ ID NO: 63, preferably SEQ ID NO: 64, preferably SEQ ID NO: 65, preferably SEQ ID NO: 66, preferably SEQ ID NO: 67.

[0140] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 63, for example, one of SEQ ID NOs: 198-200, or a biologically active variant of that fragment.

[0141] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 64, for example, one of SEQ ID NOs: 201 to 203, or a biologically active variant of that fragment.

[0142] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 65, for example SEQ ID NO: 204, or a biologically active variant of that fragment.

[0143] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 66, for example, one of SEQ ID NOs: 205 to 208, or a biologically active variant of that fragment.

[0144] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 67, for example, one of SEQ ID NOs: 209 to 215, or a biologically active variant of that fragment.

[0145] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 68, for example, one of SEQ ID NOs: 216 to 219, or a biologically active variant of that fragment.

[0146] Preferably, the peptide comprises a biologically active fragment of a region of SEQ ID NO: 69, for example SEQ ID NO: 220, or a biologically active variant of that fragment.

[0147] The present invention also provides a composition comprising at least one bioactive peptide of the present invention, wherein the peptide comprises a bioactive fragment of SEQ ID NO: 15 or a homolog thereof. The present invention also provides a composition comprising at least two, preferably three, preferably four, preferably five, preferably six, preferably seven, preferably eight, preferably nine, or preferably ten, peptides of the present invention, each of which comprises a bioactive fragment of SEQ ID NO: 15 or a homolog thereof. Preferably, the composition comprises a first peptide comprising a bioactive fragment of a first region selected from SEQ ID NOs: 63-69 and a second peptide comprising a bioactive fragment of a second region selected from SEQ ID NOs: 63-69. Preferably, the composition comprises a first bioactive peptide comprising a first bioactive fragment (or a bioactive variant of the fragment) selected from SEQ ID NOs: 198-220 and a second bioactive peptide comprising a second bioactive fragment (or a bioactive variant of the fragment) selected from SEQ ID NOs: 198-220.

[0148] Homologues of rice protein 6 (SEQ ID NO: 15) include Oryza rufipogon, Oryza officinalis, and Hordeum vulgare subsp. vulgare (SEQ ID NOs: 264-266).

[0149] [SEQ ID NO: 16 (Bacterial Protein 1-P0C1U8)] Preferably, the peptide comprises a biologically active fragment of the protein of SEQ ID NO: 16 or a homologue thereof.

[0150] Preferably, the peptide comprises a region of SEQ ID NO: 16, ie a biologically active fragment of a region of SEQ ID NO: 70. Typically, the peptide is a biologically active variant of SEQ ID NO: 221 or a fragment.

[0151] The present invention also provides compositions comprising at least one biologically active peptide of the present invention, wherein the peptide comprises a biologically active fragment of SEQ ID NO: 16 or a homolog thereof. The present invention also provides compositions comprising at least two peptides of the present invention, at least one of which comprises a fragment of SEQ ID NO: 16 or a homolog thereof, e.g., SEQ ID NO: 212, or a biologically active variant of that fragment.

[0152] Homologs of bacterial protein 1 (SEQ ID NO: 16) include: >gi|580560623|gb|EVF84961.1|Glutamyl endopeptidase [Staphylococcus aureus COAS6020] >gi|580687002|gb|EVH10169.1|Glutamyl endopeptidase [Staphylococcus aureus UCIM6080] >gi|751815683|gb|KIN24957.1|Glutamyl endopeptidase [Staphylococcus aureus MRSA_CVM43477] >gi|781884797|dbj|BAR08486.1|Glutamyl endopeptidase precursor [Staphylococcus aureus subsp. aureus] >gi|781887762|dbj|BAR11210.1|Glutamyl endopeptidase precursor [Staphylococcus aureus subsp. aureus] Includes:

[0153] The present invention also provides bioactive compositions comprising at least one, and preferably a plurality, of bioactive peptides of the present invention, each of which comprises a bioactive fragment of a protein described herein. In one embodiment, the protein is selected from SEQ ID NOs: 1-16. Typically, the or each peptide of the present invention is selected from or comprises a bioactive fragment selected from SEQ ID NOs: 71-220, or a bioactive variant of that fragment.

[0154] In one embodiment, the composition comprises a peptide of the invention, wherein the peptide comprises a sequence selected from SEQ ID NOs: 17-220, 268-352 and 356-424.

[0155] In one embodiment, the composition comprises a peptide of the invention, wherein the peptide consists essentially of a sequence selected from SEQ ID NOs: 17-220, 268-352 and 356-424.

[0156] Typically the or each peptide of the invention is selected from or comprises a biologically active fragment selected from SEQ ID NOs: 71-107 and 110-111 or a biologically active variant of said fragment.

[0157] Typically the or each peptide of the invention is selected from or comprises an anti-inflammatory fragment selected from SEQ ID NOs: 108-109 and 112-220 or an anti-inflammatory variant of said fragment.

[0158] In embodiments, the bioactive peptides, variants or fragments of the invention are anti-inflammatory.

[0159] Preferably, the composition comprises at least two distinct peptides of the invention.

[0160] Preferably, the composition comprises at least three distinct peptides of the invention.

[0161] Preferably, the composition comprises at least four distinct peptides of the invention.

[0162] Preferably, the composition comprises at least five distinct peptides of the invention.

[0163] Preferably, the composition comprises at least six distinct peptides of the invention.

[0164] Preferably, the composition comprises at least seven distinct peptides of the invention.

[0165] Preferably, the composition comprises at least eight distinct peptides of the invention.

[0166] Preferably, the composition comprises at least 9 distinct peptides of the invention.

[0167] Preferably, the composition comprises at least 10 distinct peptides of the invention.

[0168] In one embodiment, the invention includes a composition comprising one or more of SEQ ID NOs: 71-107 and 110-111, or anti-inflammatory variants of fragments thereof, or a mixture of anti-inflammatory fragments and variants thereof.

[0169] In one embodiment, the composition comprises at least one, two, three, four, five or all of SEQ ID NOs: 75, 91, 92, 93, 110 and 111.

[0170] In one embodiment, the composition comprises substantially all of the fragments SEQ ID NOs: 71-107 and 110-111.

[0171] In one embodiment, the invention includes a composition comprising one or more of SEQ ID NOs: 108-109 and 112-220, or anti-inflammatory variants of fragments thereof, or a mixture of anti-inflammatory fragments and variants thereof.

[0172] In one embodiment, the composition comprises at least one, two or three of SEQ ID NOs:108, 109 and 144.

[0173] In one embodiment, the composition of the invention is enriched in peptides having a molecular weight of less than 10 KD. In one embodiment, the composition is depleted of cellular debris.

[0174] In one embodiment, the composition of the present invention is a powder.

[0175] In one embodiment, the invention includes a composition comprising substantially all of the fragments SEQ ID NOs: 108-109 and 112-220, or anti-inflammatory variants of said fragments, or a mixture of anti-inflammatory fragments and variants thereof.

[0176] In one embodiment, the composition is edible (eatable). In one embodiment, the composition is a food or beverage. In one embodiment, the composition is a personal care composition. In one embodiment, the composition is a pharmaceutical composition. In one embodiment, the composition is a dietary supplement. In one embodiment, the composition is a solid. In one embodiment, the composition is a semi-solid (i.e., a cream, gel, or lotion). In one embodiment, the composition is a liquid.

[0177] The present invention also relates to an edible product comprising the peptide of the present invention. Preferably, the edible product is artificial.

[0178] The present invention also relates to an edible product comprising a composition of the peptides of the present invention. Preferably, the edible product is artificial.

[0179] Preferably, the edible product is a food product for human or animal (mammal) consumption.

[0180] In one embodiment, the artificial edible product is a beverage. In one embodiment, the artificial edible product is a bakery product. In one embodiment, the artificial edible product is a dairy product. In one embodiment, the artificial edible product is a snack product. In one embodiment, the artificial edible product is a baked extruded food product. In one embodiment, the artificial edible product is a milk powder. In one embodiment, the artificial edible product is an infant formula product. In one embodiment, the artificial edible product is a confectionery product. In one embodiment, the artificial edible product is yogurt. In one embodiment, the artificial edible product is a yogurt drink. In one embodiment, the artificial edible product is an ice cream product. In one embodiment, the artificial edible product is a frozen food product. In one embodiment, the artificial edible product is a breakfast cereal. In one embodiment, the artificial edible product is bread. In one embodiment, the artificial edible product is a flavored milk drink. In one embodiment, the artificial edible product is a confectionery bar. In one embodiment, the artificial edible product is tea or a tea product. In one embodiment, the artificial edible product is a baked extruded snack product. In one embodiment, the artificial edible product is a fried snack product. In one embodiment, the artificial edible product is a dietary supplement. In one embodiment, the artificial edible product is a sports nutrition product. In one embodiment, the artificial edible product is a baby food. In one embodiment, the artificial edible product is a specialty food for immunocompromised individuals. In one embodiment, the artificial edible product is a geriatric food.

[0181] The present invention also relates to artificial personal care compositions comprising the peptides of the present invention.

[0182] The present invention also relates to artificial personal care compositions comprising compositions of the peptides of the present invention.

[0183] In one embodiment, the personal care composition is a skin care product. In one embodiment, the personal care composition is a hair care product. In one embodiment, the personal care composition is a dentifrice product. In one embodiment, the personal care composition is a fragrance product. In one embodiment, the personal care composition is a deodorant product. In one embodiment, the personal care composition is an antiperspirant product. In one embodiment, the personal care composition is a soap. In one embodiment, the personal care composition is a liquid soap. In one embodiment, the personal care composition is a cream. In one embodiment, the personal care composition is a lotion. In one embodiment, the personal care composition is a gel. In one embodiment, the personal care composition is a powder.

[0184] The present invention also relates to a peptide of the invention for use in the treatment or prevention of inflammation in a mammal.

[0185] The present invention also relates to compositions of the peptides of the invention for use in treating or preventing inflammation in a mammal.

[0186] The present invention also relates to a peptide of the invention for use in the treatment or prevention of an inflammatory disorder in a mammal.

[0187] The present invention also relates to compositions of the peptides of the present invention for use in the treatment or prevention of inflammatory disorders in mammals.

[0188] In one embodiment, the inflammation is symptomatic inflammation.

[0189] In one embodiment, the inflammatory disorder is an inflammatory disorder of the joints. In one embodiment, the inflammatory disorder is an inflammatory disorder of the cardiovascular system. In one embodiment, the inflammatory disorder is an autoimmune disease. In one embodiment, the inflammatory disorder is an inflammatory disorder of the lungs and airways. In one embodiment, the inflammatory disorder is an inflammatory disorder of the intestinal tract. In one embodiment, the inflammatory disorder is dermatitis. In one embodiment, the inflammatory disorder is acne vulgaris. In one embodiment, the inflammatory disorder is psoriasis. In one embodiment, the inflammatory disorder is rheumatoid arthritis. In one embodiment, the inflammatory disorder is cardiovascular disease. In one embodiment, the inflammatory disorder is atherosclerosis. In one embodiment, the inflammatory disorder is type 1 diabetes. In one embodiment, the inflammatory disorder is Graves' disease. In one embodiment, the inflammatory disorder is Guillain-Barré disease. In one embodiment, the inflammatory disorder is lupus. In one embodiment, the inflammatory disorder is psoriatic arthritis. In one embodiment, the inflammatory disorder is ulcerative colitis. In one embodiment, the inflammatory disorder is asthma. In one embodiment, the inflammatory disorder is cystic fibrosis. In one embodiment, the inflammatory disorder is COPD. In one embodiment, the inflammatory disorder is emphysema. In one embodiment, the inflammatory disorder is acute respiratory distress syndrome. In one embodiment, the inflammatory disorder is colitis. In one embodiment, the inflammatory disorder is inflammatory bowel disease.

[0190] The present invention also relates to a peptide of the invention for use in the treatment or prevention of pain in a mammal.

[0191] The present invention also relates to compositions of the peptides of the invention for use in treating or preventing pain in a mammal.

[0192] The present invention also relates to a peptide of the invention for use in the treatment or prevention of a metabolic disorder in a mammal.

[0193] The present invention also relates to compositions of the peptides of the present invention for use in the treatment or prevention of metabolic disorders in mammals.

[0194] In one embodiment, the metabolic disorder is prediabetes. In one embodiment, the metabolic disorder is diabetes. In one embodiment, the metabolic disorder is type 1 diabetes. In one embodiment, the metabolic disorder is type 2 diabetes. In one embodiment, the metabolic disorder is metabolic syndrome. In one embodiment, the metabolic disorder is obesity. In one embodiment, the metabolic disorder is diabetic dyslipidemia. In one embodiment, the metabolic disorder is hyperlipidemia. In one embodiment, the metabolic disorder is hypertension. In one embodiment, the metabolic disorder is hypertriglyceridemia. In one embodiment, the metabolic disorder is hyperfattyacidemia. In one embodiment, the metabolic disorder is hypercholerterolemia. In one embodiment, the metabolic disorder is hyperinsulinemia. In one embodiment, the metabolic disorder is MODY.

[0195] The present invention also relates to a peptide of the invention for use in maintaining or restoring intestinal health in a mammal.

[0196] The present invention also relates to compositions of the peptides of the invention for use in maintaining or restoring intestinal health in mammals.

[0197] The present invention also relates to a peptide of the invention for use in maintaining or restoring muscle health (eg, lean tissue mass) in a mammal.

[0198] The present invention also relates to compositions of the peptides of the invention for use in maintaining or restoring muscle health (eg, lean tissue mass) in a mammal.

[0199] The present invention also relates to pharmaceutical compositions comprising a peptide of the present invention in combination with a pharmaceutically acceptable carrier.

[0200] The present invention also relates to pharmaceutical compositions comprising a composition of the peptides of the present invention in combination with a pharmaceutically acceptable carrier.

[0201] Such peptides can be used in personal care products, nutritional supplements, foods and pharmaceutical products to treat or maintain a healthy level of inflammation in the body.The present invention fulfills the huge demand for specific peptides and peptide compositions derived from food that reduce inflammation in a way that can be processed by the body without completely blocking immune response and without causing autoimmune problems and other undesirable side effects.The present invention ultimately helps the 2 billion people who suffer from inflammation.

[0202] The present invention also relates to edible products, e.g., foods, such as dairy or non-dairy products, solid foods or beverages, food additives, or nutritional supplements, comprising the compositions of the present invention. The dairy products can be milk, cheese, or yogurt. In one embodiment, the food is a snack bar. The food can comprise any amount of the compositions of the present invention, for example, from 0.1% to 30% (w / w).

[0203] The peptides of the present invention are preferably used in topical cosmetic or pharmaceutical compositions of the present invention at cosmetically or pharmaceutically effective concentrations to achieve the desired effect, between 0.00000001% (by weight) and 20% (by weight), preferably between 0.000001% (by weight) and 15% (by weight), more preferably between 0.0001% (by weight) and 10% (by weight), and even more preferably between 0.0001% (by weight) and 5% (by weight) of the total weight of the composition. Ideally, the peptides of the present invention are used in an amount of about 0.00001% w / w to about 0.5% w / w [0.1 to 5000 ppm], more preferably 0.00005 w / w to about 0.05 w / w [0.5 to 500 ppm], and most preferably about 0.0001 w / w to about 0.01 w / w [1 to 100 ppm] of the composition. Ideally, the peptides of the present invention are used in an amount of from about 0.0001% w / w to about 0.004% w / w of the composition.

[0204] For a composition of the peptides of the present invention, a typical daily dosage may be from 0.2 g to 100 g.

[0205] Dosages of the compositions of the present invention for use in foods and food supplements (i.e., edible compositions) will broadly range from 0.2 to 100 g / day. In one embodiment, the daily dosage is 1 to 10 g / day, ideally about 3 to 8 g / day. In one embodiment, the daily dosage is 10 to 20 g / day. In one embodiment, the daily dosage is 20 to 30 g / day. In one embodiment, the daily dosage is 30 to 40 g / day. In one embodiment, the daily dosage is 10 to 100 g / day. In one embodiment, the daily dosage is about 5 g / day, ideally about 3 to 8 g / day. In one embodiment, the dosage is 2 to 1000 mg / kg of body weight / day. In one embodiment, the dosage is 10 to 500 mg / kg of body weight / day. In one embodiment, the dosage is 10 to 100 mg / kg of body weight / day. In one embodiment, the dosage is 30-70 mg / day / kg body weight. The dosage of the peptides of the present invention for dietary supplements can be 0.00001 mg to 0.01 mg per day or dose.

[0206] The food may be a Food for Specific Medicinal Purposes (FSMP), which is defined as a food that is specially formulated, processed, and intended for the dietary management of a disease, injury, or medical condition in an individual being treated under medical supervision. These foods are intended for the exclusive or partial feeding of individuals whose nutritional requirements cannot be met by a normal diet. The dose may be 50 to 500 g per day depending on the patient's age and condition. When administered as a special medical food or medical food, the daily dose may be 50 to 500 g per day.

[0207] The peptides and compositions of the present invention may also be used in the non-therapeutic treatment of inflammation, including use to reduce normal, non-pathological inflammation, such as inflammation in muscles and joints after exercise.

[0208] The present invention also provides topical compositions comprising the peptides of the present invention. It will be understood that the topical composition may comprise multiple peptides, fragments, and / or variants. In one embodiment, the topical composition comprises substantially all of the peptides. In one embodiment, the topical composition comprises substantially all of the variants. The topical compositions of the present invention may be present in a formulation selected from the group including creams, multiple emulsions, anhydrous compositions, aqueous dispersions, oils, milks, balsams, foams, lotions, gels, cream gels, hydroalcoholic solutions, hydroglycolic solutions, beauty products, personal care products, hydrogels, liniments, serums, soaps, dusting powders, pastes, semisolid formulations, liniments, serums, shampoos, conditioners, ointments, optional rinse-off formulations, talc, mousses, powders, sprays, aerosols, solutions, suspensions, emulsions, syrups, elixirs, polysaccharide films, patches, gel patches, bandages, adhesive systems, water-in-oil emulsions, oil-in-water emulsions, and silicone emulsions.

[0209] In one embodiment of the present invention, the emulsion contains lipid or oil. The emulsion can be, but is not limited to, oil-in-water, water-in-oil, water-in-oil-in-water, and oil-in-water-in-silicone emulsion. The emulsion can contain a moisturizing agent. The emulsion can contain an antifoaming agent such as silicone. The emulsion can have any suitable viscosity. The emulsion can further contain an emulsifier and / or an antifoaming agent. Methods for preparing emulsions are known to those skilled in the art.

[0210] The topical composition of the present invention can be incorporated into a medical device for administration. Such devices can include, but are not limited to, fabrics, patches, bandages, gauges, socks, tights, underwear, bandages, gloves, masks, adhesive patches, non-adhesive patches, occlusive patches, and microelectric patches or suitable adhesive systems. In such an embodiment, the device is in direct contact with a keratin layer such as skin, thus releasing the peptide of the present invention. It will be understood that the topical composition can be incorporated into any suitable form as detailed herein. For example, the topical composition or peptide of the present invention can be incorporated into the device or present on the surface of the device, or can be in a cream, gel, or wax formulation or any suitable formulation as defined herein and incorporated into or on the surface of the device. The device can be adapted for adhesion or attachment to the skin.

[0211] In one embodiment, the device is adapted to release a constant amount of the composition or peptide of the present invention. It will be understood that the amount of composition contained in the sustained release system will depend, for example, on the location where the composition is to be administered, the kinetics and duration of the release of the composition of the present invention, and the nature of the condition, disorder, and / or disease to be treated and / or cared for. The device may be such that the composition is released by biodegradation of the device, or by friction between the device and the body, or by body moisture, skin pH, or body temperature.

[0212] In one embodiment of the present invention, the topical composition may further comprise at least one cosmetically or pharmaceutically acceptable excipient. The term "excipient" may be used interchangeably with "functional ingredient" or "additive." It should be understood that the topical composition of the present invention may be administered alone, but is generally administered in a mixture with a cosmetically or pharmaceutical excipient. Cosmetically or pharmaceutically acceptable excipients are well known in the art, and any known excipient may be used, provided that it is suitable for topical administration and dermatologically acceptable without excessive toxicity, incompatibility, and / or allergic reaction.

[0213] Preferably, any excipients included are present in trace amounts. The amount of excipient included depends on many factors, including the type of excipient used, the nature of the excipient, the component(s) of the topical composition, the amount of active substance or peptide in the topical composition, and / or the intended use of the topical composition. The nature and amount of any excipient should not unacceptably alter the benefits of the peptides of the present invention.

[0214] In one embodiment of the present invention, the excipient may be a suitable diluent, carrier, binder, lubricant, suspending agent, coating agent, preservative, stabilizer, dye, vehicle, solubilizer, base, emollient, emulsifier, fragrance, moisturizer, and / or surfactant.

[0215] Examples of suitable diluents include, but are not limited to, any of the diluents disclosed in U.S. Patent No. 5,629,997 or U.S. Patent No. 5,629,997. Examples include ethanol, glycerol, and water.

[0216] Examples of suitable carriers include, but are not limited to, lactose, starch, glucose, methylcellulose, magnesium stearate, mannitol, sorbitol, and any suitable carrier disclosed in US Pat. No. 5,999,237 or US Pat. No. 5,999,237.

[0217] Examples of suitable binders include, but are not limited to, starch, gelatin, natural sugars such as glucose, anhydrous lactose, free-flowing lactose, β-lactose, corn sweeteners, natural and synthetic gums such as gum arabic, tragacanth, or sodium alginate, carboxymethylcellulose, and polyethylene glycol, and any suitable binder disclosed in U.S. Patent No. 5,629,999 or U.S. Patent No. 5,629,999.

[0218] Examples of suitable lubricants include, but are not limited to, sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, and sodium chloride and any suitable lubricant disclosed in U.S. Patent No. 5,627,999 or U.S. Patent No. 5,627,999.

[0219] The carrier may be any suitable carrier known in the art or disclosed in U.S. Patent No. 5,999,237 or U.S. Patent No. 5,999,237. In some embodiments, the carrier may include liquids such as water, oils, or surfactants, including those of petroleum, animal, vegetable, or synthetic origin, polymers, oils such as peanut oil, mineral oil, castor oil, and soybean oil, alcohols, polysorbates, sorbitan esters, ether sulfates, sulfates, betaines, glycosides, maltosides, fatty alcohols, nonoxynol, polixamers, polyoxyethylene, polyethylene glycol, dextrose, glycerol, or digitonin. It is understood that the carrier is dermatologically acceptable. Preferred carriers include emulsions such as oil-in-water, water-in-oil, water-in-oil-in-water, and oil-in-water-in-silicone emulsions. The emulsion may further contain an emulsifier and / or an antifoaming agent.

[0220] In one embodiment of the present invention, topical composition can further comprise one or more additional components.Topical composition of the present invention can be administered continuously, simultaneously or sequentially with one or more other additional drugs.Such additional components can be beneficial to be included in topical composition or beneficial according to the intended use of topical composition.Additional components can be active or functional or both.

[0221] Examples of such additional ingredients include, but are not limited to, one or more cleansing agents, conditioning agents, sunscreens, pigments, moisturizers, thickeners, gelling agents, essential oils, astringents, dyes, anti-caking agents, anti-foaming agents, binders, additives, buffers, chelating agents, topical analgesics, film formers or materials, bulking agents, polymers, opacifying agents, pH adjusters, propellants, reducing agents, sequestrants, skin bleaching and lightening agents, skin conditioning agents, aloe vera, healing agents, soothing agents, smoothing agents, pantothenic acid, therapeutic agents, thickeners, vitamins, colorants, pharmaceuticals, preservatives, anti-foaming agents, buffers, astringents, polymers, pH adjusters, deodorants, or any other dermatologically acceptable carrier or surfactant.

[0222] It should be understood that a listed additional ingredient may provide more than one benefit. The classification given herein is merely for clarity and convenience and is not intended to limit the additional ingredient to that particular application or category listed.

[0223] Any additional ingredients must be suitable for application to the skin without undue toxicity, incompatibility and / or allergic reaction.

[0224] In some embodiments, the additional ingredient has glucose transport activity or supports glucose transport activity. In some embodiments, the additional ingredient has anti-inflammatory activity or supports anti-inflammatory activity. In some embodiments, the additional ingredient has anti-aging activity or supports anti-aging activity. In some embodiments, the additional ingredient is for the health and / or development of the keratin layer, skin health and / or development, and / or muscle health, recovery, and / or development. The active agent can be a pharmacological enhancer. Such active agents are known and commercially available. In such cases, the topical composition of the present invention can be administered continuously, simultaneously, or sequentially with one or more other active agents.

[0225] In some embodiments, the additional ingredient can be farnesol ([2E,6E]-3,7,11-trimethyl-2,6,10,dodecatrien-1-ol), phytantriol (3,7,11,15,tetramethylhexadecane-1,2,3-triol), desquamation actives, enzymes, enzyme inhibitors, enzyme activators, plant and marine extracts, anti-acne actives, anti-wrinkle or anti-atrophy actives, antioxidants / radical scavengers, chelating agents, flavonoids, anti-inflammatory agents, anti-cellulite deposit agents, topical anesthetics, tanning actives, skin lightening agents, skin healing agents, bisabolol, antibacterial or antifungal actives, sunscreen actives, particulate materials, conditioning agents, structuring agents, thickeners.

[0226] The desquamation active can be any suitable agent that enhances the appearance or texture of the skin, such as those disclosed in US Pat. No. 5,629,999 or US Pat. No. 5,629,999.

[0227] Examples of anti-acne actives are as disclosed in US Pat. No. 5,629,999 or US Pat. No. 5,629,999 and include resorcinol, salicylic acid, erythromycin, zine, sulfur, and benzoyl peroxide.

[0228] Examples of thickeners are as disclosed in Patent Document 1 or Patent Document 2, and include carboxylic acid polymers, cross-linked polyacrylate polymers, polyacrylamide polymers, and polysaccharides.

[0229] Examples of conditioning agents are as disclosed in US Pat. No. 5,699,299 or US Pat. No. 5,699,299 and include humectants, moisturizers or skin conditioners.

[0230] Examples of structuring agents are as disclosed in US Pat. No. 5,629,999 or US Pat. No. 5,629,999, and include any agent that provides rheological characteristics to the composition and contributes to the stability of the composition.

[0231] Any suitable antibacterial or antifungal active agent may be used, examples of which are disclosed in U.S. Patent No. 5,629,999 or U.S. Patent No. 5,629,999. Such active agents are capable of destroying microorganisms or preventing their growth or action. Examples include, but are not limited to, beta-lactam drugs, quinolones, tetracyclines, erythromycin, streptomycin sulfate, salicylic acid, and benzoyl peroxide.

[0232] Examples of particulate materials include metal oxides. Examples of anti-lipid deposition agents include xanthines. Examples of tanning actives include 1,3-dihydroxy-2-propanone and those disclosed in U.S. Patent No. 5,629,997 or U.S. Patent No. 5,629,997. Examples of local anesthetics include benzocaine, lidocaine, and bupivacaine and those disclosed in U.S. Patent No. 5,629,997 or U.S. Patent No. 5,629,997.

[0233] Examples of skin lightening agents include any agent known in the art, such as kojic acid, ascorbic acid, and those disclosed in US Pat. No. 5,629,999 or US Pat. No. 5,629,999.

[0234] Examples of sunscreen actives include any suitable organic or inorganic sunscreen actives, including metal oxides, 2-ethylhexyl-p-methoxycinnamate, and those disclosed in U.S. Patent No. 5,629,999 or U.S. Patent No. 5,629,999.

[0235] Examples of skin healing agents include panthenoic acid, as disclosed in US Pat. No. 5,627,999 or US Pat. No. 5,627,999.

[0236] Examples of anti-inflammatory agents include any agent that enhances the appearance, brightness, or color of the skin, including, but not limited to, corticosteroids, hydrocortisone, nonsteroidal agents such as ibuprofen and aspirin, and those disclosed in U.S. Patent No. 5,627,999 or U.S. Patent No. 5,627,999.

[0237] Examples of flavonoids include flavanones, methoxyflavonones, unsubstituted chalcones and mixtures thereof, as well as those disclosed in US Pat. No. 5,629,999 or US Pat. No. 5,629,999.

[0238] Examples of enzymes include lipase, protease, catalase, superoxide dismutase, amylase, peroxidase, glucuronidase, ceramidase, and hyaluronidase. Examples of enzyme inhibitors include trypsin inhibitor, Bowman-Birk inhibitor, chymotrypsin inhibitor, plant extract, flavonoid, quercetin chalcone, and those disclosed in U.S. Patent No. 5,629,297 or U.S. Patent No. 5,629,297, and mixtures thereof. Examples of enzyme activators include coenzyme A, Q10 (ubiquinone), glycyrrhizin, berberine, chrysin, and those disclosed in U.S. Patent No. 5,629,297 or U.S. Patent No. 5,629,297, and mixtures thereof.

[0239] Examples of anti-wrinkle or anti-atrophy actives include sulfur-containing D and L amino acids, especially N-acyl derivatives such as N-acetyl-L-cysteine, hydroxyl acids, phytic acid, lipoic acid, lysophosphatidic acid, skin exfoliants, vitamin B3, retinoids and those disclosed in US Pat. No. 5,629,999 or US Pat. No. 5,629,999 and mixtures thereof.

[0240] The antioxidant / radical scavenger agent can be any agent useful in providing protection from UV radiation or other environmental agents that can cause skin damage, such as those disclosed in U.S. Patent No. 5,999,299 or U.S. Patent No. 5,999,299. Examples of antioxidant / radical scavengers include ascorbic acid, its salts and derivatives (vitamin C), tocopherol, its salts and derivatives (vitamin E), butylated hydroxylbenzoic acid and its salts, peroxides, gallic acid and alkyl esters, sorbic acid, lipoic acid, amines, lycine pidolate, arginine pilolate, nordihydroguaiaretic acid, bioflavonoids, curcumin, lysine, methionine, proline, superoxide dismutase, silymarin, tea extracts, and mixtures thereof.

[0241] Examples of chelating agents include EDTA, NTA, hydroxamic acid, phytic acid, lactoferrin, and those disclosed in Patent Document 1 or Patent Document 2, and mixtures thereof. A chelating agent refers to an agent that can remove metal ions by forming a complex so that the metal ions cannot participate in or catalyze chemical reactions. Chelating agents are useful for protection from UV radiation or other environmental agents that can cause skin damage.

[0242] It will be understood that multiple additional ingredients may be added. The amount of additional ingredient may be about 0.001% to about 50% by weight of the composition, preferably about 0.01% to about 20%, preferably about 0.1% to about 10%, about 0.5% to about 10%, about 1% to about 5%, preferably 2% by weight of the composition. The amount of additional ingredient included depends on numerous factors, including the type of additional ingredient used, the nature of the additional ingredient, the ingredient(s) of the topical composition, the amount of active substance or peptide in the topical composition, and / or the intended use of the topical composition. The nature and amount of any additional ingredient should not unacceptably alter the benefits of the peptides of the present invention.

[0243] The topical composition may be alcohol-free.

[0244] In some embodiments of the present invention, the composition further comprises one or more additional active agents in addition to the peptide of the present invention (also known as the active agent of the composition). Additionally or alternatively, the composition may be administered with one or more other additional active agents. Typically, such additional active agents are present only in trace amounts. In some embodiments, no additional active agents may be present in the composition. The amount of additional active agent included depends on numerous factors, including the type of additional active agent used, the nature of the additional active agent, the component(s) of the topical composition, the amount of active agent or peptide in the topical composition, and / or the intended use of the topical composition. The nature and amount of any additional active agent should not unacceptably alter the benefits of the peptide of the present invention.

[0245] It should be understood that an ingredient that is considered to be an "active" ingredient in one product may be a "functional" or "excipient" ingredient in another, and vice versa. It will be understood that some ingredients may serve a dual role as both an active ingredient and a functional or excipient ingredient.

[0246] Examples of additional active agents include glucose transport promoters, skin nutritional supplements, agents for treating and / or caring for skin, anti-inflammatory agents, anti-aging agents, cell growth promoters and pharmacological enhancers.Such agents are well known in the art, and it will be understood that any suitable additional active agent can be used.Additional active agents for treating and / or healing skin can include collagen synthesis agents, retinoids, exfoliants, anti-lipid deposition agents, elastase inhibitors, melanin synthesis stimulators or inhibitors, self-tanning agents, anti-aging agents, antibacterial agents, antifungal agents, fungistatic agents, bactericides and healing agents.Active agents also include anti-inflammatory agents.

[0247] Any additional active agent must be suitable for application to the skin without undue toxicity, incompatibility and / or allergic reaction.

[0248] It will be understood that the classifications given herein are for clarity and convenience only and are not intended to limit the additional ingredients, excipients or active substances to that particular application or category listed.

[0249] In a particularly preferred embodiment, the method and use of the present invention comprises administering the peptide or composition of the present invention in combination with one or more other active agents, such as existing growth promoters or pharmacological enhancers available on the market.In such cases, the compound of the present invention can be administered continuously, simultaneously or sequentially with one or more other active agents.

[0250] The effect of the present invention is achieved by topically applying or administering the topical composition of the present invention described herein to humans, animals or patients who need treatment or care.Topical delivery preferably refers to delivery to keratin layers such as skin, hair and / or nails, but can also refer to delivery to the body cavity lined with epithelial cells, such as lung or respiratory tract, gastrointestinal tract, buccal cavity.Effect can be limited to the surface of the skin, or can be in the skin, or can be a combination of both.

[0251] The topical composition of the present invention is administered in a cosmetically or pharmaceutically effective amount. In other words, in an amount that is non-toxic but sufficient to provide the desired effect. It will be understood that a person skilled in the art will be able to determine the appropriate dosage of the topical composition of the present invention to administer without undue experimentation. Alternatively, a physician will determine the actual dosage that is most suitable for a patient depending on the individual condition, the disease or disorder to be treated or cared for, and the age, weight, and / or health of the individual. This will depend on various factors, including the activity of the specific compound used, the metabolic stability and duration of action of the compound, age, weight, general health, sex, diet, mode and time of administration, excretion rate, drug combination, the severity of the individual condition, and the therapy the individual is undergoing. Of course, there may be individual cases where higher or lower dosage ranges are merited, and such are within the scope of the present invention. For example, the composition may be administered at a dose of 0.1 to 30 mg / kg, more preferably 0.1 to 20 mg / kg body weight, more preferably 0.1 to 10 mg / kg body weight, preferably 0.01 to 50 mg / kg body weight, such as 0.1 to 5 mg / kg body weight. In an exemplary embodiment, one or more doses of 10 to 300 mg / day, or more preferably 10 to 150 mg / day, are administered to the patient. The amount and frequency are as optimal for the purpose. The frequency of application or administration can vary widely depending on the needs of each subject, with recommended application or administration ranges from once a month to 10 times a day, preferably once a week to four times a day, more preferably three times a week to three times a day, and even more preferably once or twice a day.

[0252] In a preferred embodiment, repeated use of the topical composition is provided.

[0253] The topical composition may be applied by rubbing or massaging into the keratinous tissue, skin, or area of ​​the body to be treated or cared for. In some embodiments, the composition remains on the area of ​​the body or is not removed therefrom. In other embodiments, the composition is removed after a period of time, such as, but not limited to, about 2 minutes to 60 minutes, about 5 minutes to about 30 minutes, and preferably about 10 minutes to about 20 minutes. The composition may be removed immediately after application. In some embodiments of the present invention, the composition of the present invention may be applied to the area to be treated by a means to achieve greater penetration of the composition and / or peptide of the present invention, such as, but not limited to, iontophoresis, sonophoresis, electroporation, microelectric patching, mechanical pressure, osmotic gradient, occlusive therapy, microinjection, or needle-free injection with pressure, such as oxygen pressure injection, or any combination thereof.

[0254] The peptides of the present invention are used in the topical cosmetic or pharmaceutical compositions of the present invention in a preferred form at a cosmetically or pharmaceutically effective concentration to achieve the desired effect, between 0.00000001% (by weight) and 20% (by weight), preferably between 0.000001% (by weight) and 15% (by weight), more preferably between 0.0001% (by weight) and 10% (by weight), and even more preferably between 0.0001% (by weight) and 5% (by weight) of the total weight of the composition.

[0255] In some embodiments of the present invention, the compositions may be delivered in any one of liposomes, mixed liposomes, oleosomes, niosomes, ethosomes, millicapsules, capsules, macrocapsules, nanocapsules, nanostructured lipid carriers, sponges, cyclodextrins, vesicles, micelles, surfactant mixed micelles, surfactant-phospholipid mixed micelles, millispheres, spheres, lipospheres, particles, nanospheres, nanoparticles, milliparticles, solid nanoparticles, and microemulsions, including water-in-oil microemulsions with reverse micelle internal structures, and nanoemulsions, microspheres, and microparticles.

[0256] A variety of methods are available for preparing liposomes. See, e.g., (Illegible text - likely OCR error) ...

[0257] These delivery systems can be adapted to achieve greater penetration of the compounds and / or peptides of the present invention. This can improve pharmacokinetics and pharmacodynamics. The delivery system can be a sustained release system in which the compounds or peptides of the present invention are gradually released for a certain period of time, preferably at a constant release rate over a certain period of time. The delivery system is prepared by a method known in the art. The amount of peptide contained in the sustained release system depends on the location and release period of the composition to be delivered and the type of condition, disease and / or disorder to be treated or cared for.

[0258] The topical compositions of the present invention may be for human and animal use in human and veterinary medicine.

[0259] The topical compositions of the present invention may be used for pharmaceutical, personal care and / or cosmetic uses.

[0260] The compositions may be used to treat or care for any disease, disorder or condition of the skin, including, but not limited to, itches, dermatitis, allergic dermatitis, eczema, spongiosis, edema, skin cancer, ulcers, acne, scars, cellulitis, elastosis, keratosis, rosacea, varicose veins, inflammatory disorders.

[0261] Topical composition can be used to treat or care for the visible signs of aging, including but not limited to wrinkles, lines and dark circles, dryness, fine lines, blemishes, red spots, loose skin, and the conditions caused by sun exposure, stress, pollution and / dietary restrictions, including sunburn.Topical composition can also be used to delay, slow down or inhibit the skin or the occurrence of aging.Composition can be administered by medical device such as plaster or patch as described herein.

[0262] This topical composition can be used to treat or care for wounds in mammals.In another embodiment, this topical composition is used for treating or preventing the disease or condition that is characterized by damaged epithelial cells or tissue and / or damaged dermis or epithelial cells or tissue.The disease can be but is not limited to cancer and trauma.

[0263] The topical compositions may be used in the treatment or prevention of diseases or conditions characterized by lethargy or low energy levels, to treat or care for any muscle condition, to improve muscle condition in mammals, typically to promote muscle recovery after exercise, to maintain or restore muscle health (e.g., lean tissue mass) in mammals, and to enhance physical performance.

[0264] The topical compositions can be used to promote tissue growth, epithelial tissue growth, skin growth, organ growth, and other biological growth. The skin may have normal and / or abnormal pathology.

[0265] The topical compositions may also be used to treat or care for any inflammatory disorder.

[0266] A further aspect of the present invention relates to pharmaceutical compositions comprising a peptide of the present invention or a composition of a peptide of the present invention mixed with one or more pharmaceutically acceptable diluents, excipients, or carriers. While the peptides and compositions of the present invention can be administered alone, they are generally administered in admixture with a pharmaceutical carrier, excipient, or diluent, particularly for human therapy. The pharmaceutical compositions may be for human and animal use in human and veterinary medicine. Examples of such suitable excipients for the various different forms of pharmaceutical compositions described herein can be found in Non-Patent Document 14. In particular, topical delivery formulations are described in Non-Patent Document 15, the entire contents of which are incorporated herein by reference. Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical arts and are described, for example, in Non-Patent Document 16. Examples of suitable carriers include lactose, starch, glucose, methylcellulose, magnesium stearate, mannitol, sorbitol, and the like. Examples of suitable diluents include ethanol, glycerol, and water. The choice of pharmaceutical carrier, excipient, or diluent can be selected with regard to the intended route of administration and standard pharmaceutical practice. Pharmaceutical compositions can contain any suitable binder(s), lubricant(s), suspending agent(s), coating agent(s), solubilizing agent(s) as, or in addition to, the carrier, excipient, or diluent. Examples of suitable binders include starch, gelatin, natural sugars such as glucose, anhydrous lactose, free-flowing lactose, β-lactose, corn sweeteners, natural and synthetic gums such as gum arabic, tragacanth, or sodium alginate, carboxymethylcellulose, and polyethylene glycol. Examples of suitable lubricants include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, etc. Preservatives, stabilizers, dyes, and even flavoring agents can be provided in the pharmaceutical composition. Examples of preservatives include sodium benzoate, sorbic acid and esters of p-hydroxybenzoic acid. Antioxidants and suspending agents may also be used.

[0267] The peptides or compositions of the present invention may be adapted for topical, oral, rectal, parenteral, intramuscular, intraperitoneal, intraarterial, intrabronchial, subcutaneous, intradermal, intravenous, intranasal, vaginal, buccal, or sublingual administration. For oral administration, compressed tablets, pills, tablets, gels, drops, and capsules are particularly used. Preferably, these compositions contain 1 to 250 mg, more preferably 10-100 mg, of active ingredient per dose. Other forms of administration include solutions or emulsions that may be injected intravenously, intraarterially, subcutaneously, intradermally, intraperitoneally, or intramuscularly and are prepared from sterile or sterilizable solutions. Pharmaceutical compositions of the present invention may be in the form of suppositories, vaginal rings, pessaries, suspensions, emulsions, lotions, ointments, creams, gels, sprays, solutions, or dusting powders. The compositions of the present invention may be formulated for topical delivery. Topical delivery generally refers to delivery to the skin, but can also refer to delivery to epithelial cell-lined body lumens, such as the lungs or respiratory tract, the gastrointestinal tract, and the buccal cavity. In particular, topical delivery formulations are described in Non-Patent Document 15, the entire contents of which are incorporated herein by reference. Compositions or formulations for delivery to the respiratory tract are described in Non-Patent Document 17, Patent Document 13, Patent Document 14, Patent Document 15, and Patent Document 16. Compositions and formulations for delivery of active agents to the ileum, particularly the proximal ileum, include microparticles and microencapsulates in which the active agent is encapsulated within a protective matrix formed from polymers or milk proteins that are acid-resistant but tend to dissolve in the more alkaline environment of the ileum. Examples of such delivery systems are described in Patent Documents 17 and 18. An alternative to transdermal administration is through the use of a skin patch. For example, the active ingredient can be incorporated into a cream consisting of an aqueous emulsion of polyethylene glycol or liquid paraffin. The active ingredient can also be incorporated, at a concentration of between 1 and 10% by weight, into an ointment consisting of a white wax or white soft paraffin base together with such stabilizers and preservatives as may be required.

[0268] Injectable forms may contain between 10 and 1000 mg, preferably between 10 and 250 mg, of active ingredient per dose.

[0269] Compositions may be formulated in unit dosage form, ie, in the form of discrete portions containing a unit dose, or a multiple or sub-unit of a unit dose.

[0270] Those skilled in the art can easily determine the appropriate dose of one of the compositions to be administered to a subject without undue experimentation. Typically, a physician will determine the actual dosage that is most suitable for an individual patient, which will depend on various factors, including the activity of the particular compound, the metabolic stability and duration of action of the compound, age, body weight, general health, sex, diet, mode and time of administration, excretion rate, drug combinations, the severity of the individual's condition, and the therapy the individual is currently receiving. The dosages disclosed herein are exemplary of average cases. Of course, there may be individual cases where higher or lower dosage ranges are warranted, and such are within the scope of the present invention. If necessary, the agent may be administered at a dose of 0.1 to 10 mg / kg, more preferably 0.01 to 30 mg / kg, such as 0.1 to 1 mg / kg body weight. In an exemplary embodiment, one or more doses of 10 to 300 mg / day, or more preferably 10 to 150 mg / day, are administered to a patient for the treatment of inflammatory disorders.

[0271] In a particularly preferred embodiment, the methods and uses of the present invention include administering the peptide or composition of the present invention in combination with one or more other active agents, such as existing anti-inflammatory drugs or pharmacological enhancers available on the market. In such cases, the compound of the present invention can be administered continuously, simultaneously, or sequentially with one or more other active agents.

[0272] In one embodiment of the present invention, the peptide of the present invention can be administered in the form of a conjugate comprising the peptide, and optionally a linker and a partner molecule, for example, a protein such as an antibody molecule, intended to increase the half-life of the conjugate in vivo. In one embodiment, the peptide can be modified to replace one or more amino acids with amino acids used to attach to the partner molecule. For example, an amino acid can be replaced with a lysine residue for the purpose of conjugating a partner molecule such as a PEG molecule.

[0273] definition All publications, patents, patent applications and other references mentioned herein are incorporated by reference in their entirety as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference and the contents of which were set forth in full.

[0274] As used herein, unless otherwise indicated, the following terms shall have the following meanings, in addition to any broader (or narrower) meaning by which such terms are used in the art: Unless otherwise required by context, the use of the singular herein should be read to include the plural, and vice versa. The term "a" or "an" when used in reference to an entity should be read to refer to one or more of that entity. As such, the terms "a" (or "an"), "one or more," and "at least one" are used interchangeably herein.

[0275] As used herein, the term "comprise," or variations thereof, such as "comprises" or "comprising," should be read to indicate the inclusion of any enumerated integer (e.g., feature, element, characteristic, property, method / process step, or limitation) or group of integers (e.g., feature, element, feature, property, method / process step, or limitation), but not the exclusion of any other integer or group of integers. Thus, as used herein, the term "comprising" is inclusive or open-ended and does not exclude additional, unenumerated integers or method / process steps.

[0276] As used herein, the term "disease" is used to define any abnormal condition that impairs physiological function and is associated with specific symptoms. The term is used broadly to encompass any disorder, illness, disorder, pathology, condition, or syndrome in which physiological function is impaired, regardless of the nature of the etiology (or indeed whether the etiological basis of the disease has been established). Thus, it encompasses conditions resulting from infection, trauma, injury, surgery, radiation ablation, poisoning, or nutritional deficiency.

[0277] As used herein, the term "treatment" or "treating" refers to an intervention (e.g., administering a drug to a subject) that cures, alleviates, or relieves the symptoms of a disease, or eliminates (or mitigates) its cause(s) (e.g., reducing the accumulation of pathological levels of lysosomal enzymes). In this context, the term is used interchangeably with the term "therapy."

[0278] Furthermore, the term "treatment" or "treating" refers to an intervention (e.g., administration of a drug to a subject) that prevents or slows the onset or progression of a disease, or reduces its incidence (or eradicates) within the treated population. In this instance, the term "treatment" is used synonymously with the term "prophylaxis."

[0279] As used herein, the term "effective amount" or "therapeutically effective amount" refers to an amount that can be administered to a subject without excessive toxicity, irritation, allergic reactions, or other problems or complications, commensurate with the benefit / risk ratio, but sufficient to provide the desired effect, e.g., treatment or prevention, as indicated by permanent or temporary improvement of the subject's condition. The amount will vary from subject to subject, depending on the individual's age and general condition, the mode of administration, and other factors. Therefore, it is not possible to specify an exact effective amount, but those skilled in the art will be able to determine an appropriate "effective" amount in any individual case using routine experimentation and general background knowledge. In this context, therapeutic results include eradicating or alleviating symptoms, reducing pain or discomfort, prolonging survival, improving mobility, and other markers of clinical improvement. The therapeutic result does not necessarily have to be a complete cure.

[0280] The term "mammal" should be understood to mean higher mammals, especially humans, but also includes non-mammals such as fish.

[0281] As used herein, the term "peptide" generally refers to a polymer composed of up to 50 amino acid monomers linked via peptide bonds. Peptides can be 3 to 50 amino acids in length. Peptides can be 4 to 50 amino acids in length. Peptides can be 5 to 50 amino acids in length. Peptides can be 7 to 50 amino acids in length. Peptides of and for use in the present invention (including fragments and variants thereof) can be produced completely or partially by chemical synthesis or by expression from nucleic acids. For example, peptides of and for use in the present invention can be readily prepared according to well-established standard solution-phase or, preferably, solid-phase peptide synthesis methods known in the art (see, e.g., Non-Patent Document 18). If necessary, any of the peptides used in the present invention can be chemically modified to increase their stability. Chemically modified peptides or peptide analogs include any functional chemical equivalent of a peptide characterized by its increased stability and / or efficacy in vivo or in vitro for practicing the present invention. The term peptide analog also refers to any amino acid derivative of a peptide as described herein. Peptide analogs can be produced by procedures including, but not limited to, side chain modifications, the incorporation of unnatural amino acids and / or their derivatives during peptide synthesis, and the use of crosslinkers and other methods to impose conformational constraints on peptides or their analogs. Examples of side chain modifications include reductive alkylation by reaction with an aldehyde followed by reduction with NaBH4, amidation with methylacetimidate, acetylation with acetic anhydride, carbamylation of the amino group with cyanic acid, trinitrobenzylation of the amino group with 2,4,6-trinitrobenzenesulfonic acid (TNBS), alkylation of the amino group with succinic anhydride and tetrahydrophthalic anhydride, and pyridoxylation of lysine with pyridoxa-5'-phosphate followed by reduction with NABH4. The guanidino group of arginine residues can be modified by the formation of heterocyclic condensation products with reagents such as 2,3-butanedione, phenylglyoxal, and glyoxal.Carboxyl groups can be modified by carbodiimide activation via o-acylisourea formation followed by subsequent derivatization, for example, to the corresponding amide. Sulfhydryl groups can be modified by methods such as carboxymethylation with iodoacetic acid or iodoacetamide, performic acid oxidation to cysteic acid, mixed disulfide formation with other thiol compounds, reaction with maleimide, maleic anhydride or other substituted maleimides, formation of mercury derivatives using 4-chloromercurybenzoic acid, 4-chloromercuryphenylsulfonic acid, phenylmercury chloride, 2-chloromercuric-4-nitrophenol and other mercuric acids, and carbamylation with cyanic acid at alkaline pH. Tryptophan residues can be modified by, for example, oxidation with N-bromosuccinimide or alkylation of the indole ring with 2-hydroxy-5-nitrobenzyl bromide or sulfonyl halides. Tyrosine residues can be altered by nitration with tetranitromethane to form 3-nitrotyrosine derivatives. Modification of the imidazole ring of histidine residues can be achieved by alkylation with iodoacetic acid derivatives or N-carbethoxylation with diethylpyrocarbonate. Examples of incorporating unnatural amino acids and derivatives during peptide synthesis include, but are not limited to, norleucine, 4-aminobutyric acid, 4-amino-3-hydroxy-5-phenylpentanoic acid, 6-aminohexanoic acid, t-butylglycine, norvaline, phenylglycine, ornithine, sarcosine, 4-amino-3-hydroxy-6-methylheptanoic acid, 2-thienylalanine, and / or the D-isomers of amino acids. Peptide structural modifications include the generation of retro-inverso peptides containing reverse sequences encoded by D-amino acids.

[0282] "Modified peptide": In one embodiment of the present invention, the peptide is a modified peptide. The term "modified peptide" is used synonymously with the term "derivative of a peptide." Modified peptides include peptides substituted with one or more groups as defined herein. The modification can be any modification that provides the peptides and / or compositions of the present invention with increased cell penetration ability. The modification can be any modification that increases the half-life of the compositions or peptides of the present invention. In one embodiment, the group is a protecting group. The protecting group can be an N-terminal protecting group, a C-terminal protecting group, or a side chain protecting group. The peptide can have one or more of these protecting groups. Those skilled in the art are aware of suitable techniques for reacting amino acids with these protecting groups. These groups can be added by preparative methods known in the art, for example, the methods outlined in paragraphs

[0104] to

[0107] of Patent Document 19. The group can remain on the peptide or can be removed. The protecting group can be added during synthesis. In one embodiment of the present invention, the peptides may be substituted with one or more groups selected from saturated or unsaturated, straight-chain or branched, long-chain or short-chain aminoacyl groups having 1 to 29 carbon atoms, substituted or unsubstituted with hydroxyl, amino, aminoacyl, sulfate, or sulfide groups. N-acyl derivatives include acyl groups derived from acetic acid, capric acid, lauric acid, myristic acid, octanoic acid, palmitic acid, stearic acid, behenic acid, linoleic acid, linolenic acid, lipoic acid, oleic acid, isostearic acid, elaidic acid, 2-ethylhexane acid, coconut oil fatty acid, tallow fatty acid, hardened tallow fatty acid, palm kernel fatty acid, lanolin fatty acid, or similar acids. These may be substituted or unsubstituted. If substituted, they are preferably substituted with hydroxyl or sulfur-containing groups such as, but not limited to, SO3H, SH, or SS. In one embodiment of the present invention, the peptide is R1-X-R2. The R1 and / or R2 groups are attached to the amino terminus (N-terminus) and carboxyl terminus (C-terminus) of the peptide sequence, respectively. In one embodiment, the peptide is R1-X.Alternatively, the peptide is X-R2. Preferably, R1 is H, C. 1~4 In one embodiment, R1 is selected from the group formed by H, acyclic substituted or unsubstituted aliphatic groups, substituted or unsubstituted alicyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, t-butyloxycarbonyl, 9-fluorenylmethyloxycarbonyl (Fmoc), and R5-CO-, wherein R5 is H, acyclic substituted or unsubstituted aliphatic groups, substituted or unsubstituted alicyclyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, and R2 is selected from the group formed by -NR3R4, -OR3 and -SR3, where R3 and R4 are independently selected from the group formed by H, acyclic substituted or unsubstituted aliphatic groups, substituted or unsubstituted alicyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aryl and substituted or unsubstituted aralkyl, with the proviso that R1 and R2 are not α-amino acids. According to another preferred embodiment, R2 is -NR3R4, -OR3 or -SR3, where R3 and R4 are independently H, substituted or unsubstituted C1-C 24 Alkyl, substituted or unsubstituted C2-C 24 Alkenyl, t-butyloxycarbonyl, 9-fluorenylmethyloxycarbonyl (Fmoc), substituted or unsubstituted C2-C 24 Alkynyl, substituted or unsubstituted C3-C 24 Cycloalkyl, substituted or unsubstituted C5-C 24 Cycloalkenyl, substituted or unsubstituted C8-C 24 Cycloalkynyl, substituted or unsubstituted C6-C 30 Aryl, substituted or unsubstituted C7-C 24aralkyl, 3-10 membered substituted or unsubstituted heterocyclyl rings, and substituted or unsubstituted heteroarylalkyl of 2 to 24 carbon atoms and 1 to 3 atoms other than carbon, wherein the alkyl chain is of 1 to 6 carbon atoms. Optionally, R3 and R4 may be joined by a saturated or unsaturated carbon-carbon bond to form a ring together with the nitrogen atom. More preferably, R2 is -NR3R4 or -OR3, where R3 and R4 are independently H, substituted or unsubstituted C1-C 24 Alkyl, substituted or unsubstituted C2-C 24 Alkenyl, substituted or unsubstituted C2-C 24 Alkynyl, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 15

[0023] Preferably, R3 and R4 are selected from the group formed by aryl and 3- to 10-membered substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroaryl alkyl having a 3- to 10-membered ring, and alkyl of 1 to 6 carbon atoms. More preferably, R3 and R4 are selected from the group formed by H, methyl, ethyl, hexyl, dodecyl, or hexadecyl. Even more preferably, R3 is H, and R4 is selected from the group formed by H, methyl, ethyl, hexyl, dodecyl, or hexadecyl. According to an even more preferred embodiment, R2 is selected from -OH and -NH2. According to another embodiment of the present invention, R1 is selected from the group formed by H, acetyl, lauroyl, myristoyl, or palmitoyl, and R2 is -NR3R4 or -OR3, where R3 and R4 are independently selected from H, methyl, ethyl, hexyl, dodecyl, and hexadecyl, and preferably R2 is -OH or -NH2. More preferably, R1 is acetyl or palmitoyl, and R2 is -NH2. In a preferred embodiment, the acyl group is attached to the N-terminus of at least one amino acid of the peptide. In one embodiment of the present invention, the peptide is modified to include a side chain protecting group. The side chain protecting group can be one or more of a benzyl-containing or benzyl-based group, a t-butyl-based group, a benzyloxy-carbonyl (Z) group, and an allyloxycarbonyl (alloc) protecting group. The side chain protecting group can be derived from an achiral amino acid, such as achiral glycine. The use of an achiral amino acid helps stabilize the resulting peptide and also facilitates the facile synthetic route of the present invention. Preferably, the peptide further includes a modified C-terminus, preferably an amidated C-terminus. The achiral residue can be α-aminoisobutyric acid (methylalanine). It will be understood that the specific side chain protecting group used will depend on the peptide sequence and the type of N-terminal protecting group used.

[0283] "Conjugate": In one embodiment of the present invention, the peptide is conjugated, linked, or fused to a binding partner, e.g., one or more polyethylene glycol polymers or other compounds, such as molecular weight-enhancing compounds or lipophilic groups. The molecular weight-enhancing compound is any compound that increases the molecular weight of the resulting conjugate, typically by 10% to 90% or 20% to 50%, and may have a molecular weight between 200 and 20,000, preferably between 500 and 10,000. The molecular weight-enhancing compound may be PEG, any water-soluble (amphiphilic or hydrophilic) polymer moiety, PEG homo- or copolymers, monomethyl-substituted polymers of PEG (mPEG), and polyoxyethyleneglycerol (POG), polyamino acids such as polylysine, polyglutamic acid, polyaspartic acid, especially those in the L-conformation, pharmacologically inactive proteins such as albumin, gelatin, fatty acids, polysaccharides, lipid amino acids, and dextran. The polymeric moiety can be linear or branched and can have a molecular weight of 500 to 40,000 Da, 5,000 to 10,000 Da, or 10,000 to 5,000 Da. The compound (binding partner) can be any suitable cell-permeable compound, such as tat peptide, penetratin, or pep-1. The compound (binding partner) can be an antibody molecule. The compound (binding partner) can be a lipophilic moiety or a polymeric moiety. Lipophilic and polymeric substituents are known in the art. Lipophilic substituents include N, O, or S atoms that form part of an acyl group, sulfonyl group, ester, sulfonyl ester, thioester, amide, or sulfonamide. The lipophilic moiety can include a hydrocarbon chain having 4 to 30 C atoms, preferably between 8 and 12 C atoms. It can be linear or branched, saturated or unsaturated. The hydrocarbon chain can be further substituted. It can be a cycloalkane or heterocycloalkane. The peptides may be modified at the N-terminus, C-terminus, or both. The polymer or compound (binding partner) is preferably linked to an amino, carboxyl, or thio group, and may be linked by the N-terminus or C-terminus of the side chain of any amino acid residue.The polymer or compound (binding partner) can be conjugated to the side chain of any suitable residue. The polymer or compound (binding partner) can be conjugated via a spacer. The spacer can be a natural or unnatural amino acid, succinic acid, lysyl, glutamyl, asparagyl, glycyl, β-alanyl, or γ-aminobutanoyl. The polymer or compound (binding partner) can be conjugated via an ester, sulfonyl ester, thioester, amide, carbamate, urea, or sulfonamide. Those skilled in the art will be aware of suitable means for preparing the described conjugates.

[0284] A "fragment" generally refers to a segment of a protein selected from a region of the protein selected from SEQ ID NOS: 1-16 and 353-355, particularly SEQ ID NOS: 17-70. In one embodiment, the fragment is typically 3 to 37 contiguous amino acids in length. In one embodiment, the fragment is typically 5 to 37 contiguous amino acids in length. In one embodiment, the fragment is typically 5 to 37 contiguous amino acids in length. Generally, the fragment has a charge between -9 and +3, typically a C-terminal amino acid that is not typically cysteine ​​(C) or methionine (M), and typically an N-terminal amino acid that is not typically cysteine ​​(C), histidine (H), proline (P), or threonine (T). The charge of a peptide fragment or region is determined using the method of Non-Patent Document 19.

[0285] The term "naturally occurring" as applied to a peptide means a peptide comprising (a) a fragment of a plant protein, typically a rice or pea protein or a variant of a pea protein, including lentil, sweet pea, or chickpea, or a variant of a rice protein, including oat, grass, corn, wild rice, and banana, or (b) a fragment of a plant protein, e.g., a variant of a fragment of a homologue of a plant protein. The peptides or fragments of the invention can be isolated from plant proteins or made synthetically.

[0286] "C-terminal domain" as applied to a fragment means the first three amino acids at the c-terminus of the fragment.

[0287] "N-terminal domain" as applied to a fragment means the last three amino acids at the N-terminus of the fragment.

[0288] "Bioactive" as applied to a peptide or fragment means having one or more health-promoting effects when administered to a mammal, for example, glucose transport promoting, antibacterial, anti-inflammatory, or cell growth or proliferation promoting. In one embodiment, the term "bioactive" refers to anti-inflammatory.

[0289] "Glucose transport enhancement" or "glucose transport enhancing activity" as applied to a peptide, variant, or fragment refers to a peptide, variant, or fragment that, when used at a concentration of 2 μM, is capable of increasing GLUT4 translocation into skeletal muscle compared to untreated controls in the following in vitro assay. L6-GLUT4myc cells were grown in 10% FBS and 2 μg / ml blasticidin. Cells were grown for 48-72 hours, then seeded at 15,000 cells per well in 2% FBS in 24-well plates and allowed to differentiate for 6-8 days prior to experimentation. L6-GLUT4myc cells were serum-starved for 3 hours and then incubated with 100 nM insulin for 30 minutes or with 200, 20, 2.0, and 0.2 μM SP and 2, 1, 0.5, and 0.25 mg / ml peptide compositions for 3 hours, respectively. The 3-hour incubation period was chosen based on previous findings identifying that 3-hour incubation with branched-chain amino acid containing dipeptides increases glucose uptake in L6 myotubes. Treatments were staggered to determine GLUT4myc translocation at the same time point. The amount of myc-tagged GLUT4 on the cell surface was measured by an antibody-coupled colorimetric assay. Briefly, after 30 minutes of incubation with insulin or 3 hours each with synthetic peptides or peptide compositions, L6-GLUT4myc cells were fixed by incubation with 3% paraformaldehyde (PFA). The PFA was then quenched by the addition of 0.1 M glycine solution, and the cells were blocked with 5% goat serum. Myotube monolayers were exposed to anti-myc antibody and then incubated with peroxidase-conjugated donkey anti-mouse IgG. One mL of o-phenylenediamine dihydrochloride (OPD) reagent was added to each well, and the reaction was stopped by adding 250 μl / well of 3 M HCl. To determine GLUT4 translocation to the cell surface, aliquots from each condition were examined spectrophotometrically in a plate reader using absorbance at 492 nm.Preferably, the peptide or fragment is capable of increasing GLUT4 translocation by at least 50% compared to an untreated control (ie, a relative unit increase in GLUT4 translocation of 1% to 1.5%).

[0290] "Antibacterial" or "antibacterial activity" as applied to a peptide or fragment means a peptide or fragment capable of visibly inhibiting bacterial growth in the following agar plate-based growth inhibition assay: peptide stock = 5 mg / mL dissolved in DMSO. Bacterial inoculum was adjusted to a McFarland 0.5 standard and plated on MHA plates. A blank disc was placed on the plate, and 10 μl of each compound (64 μg / mL - the highest concentration tested) was added. Plates were incubated at 37°C for 16-18 hours. Appropriate controls (DMSO; Mueller-Hinton medium alone; and two antibiotic discs - ciprofloxacin and tetracycline) were also performed.

[0291] "Anti-inflammatory" as applied to a peptide or fragment means a peptide or fragment that is capable of significantly reducing TNFα secretion by LPS-stimulated J774.2 macrophages (compared to untreated LPS-stimulated J774.2 macrophages) when the macrophages are treated with 100 μM of the peptide or fragment. J774.2 macrophages were treated with 100 μM of synthetic peptide for 24 hours and then stimulated with (A) LPS (10 ng / ml) for 5 hours or (B) LPS (10 ng / ml) for 5 hours followed by ATP (5 mM) for 1 hour. Supernatants were collected, and TNFα levels were determined by ELISA.

[0292] "Cell growth promotion" or "cell growth or proliferation promotion" as applied to a peptide or fragment refers to a peptide or fragment capable of increasing elastin production or cell proliferation in human skin treated with a 20 μM solution of the peptide or fragment in the following assay. Skin grafts were prepared from abdominoplasty surgeries. Some grafts were degreased with alcohol to obtain dehydrated skin. These grafts were maintained in maintenance medium provided by the supplier Biopredic International for 5 days. The test item was applied twice per day at 5 μL per graft. At the end of the study, two grafts were used as viability controls using MTT, and a third graft was fixed in 4% formaldehyde for histology and cell staining. At each analysis (D1 and D5), histology was performed on the degreased grafts, the test item, the DMSO 0.3% control, and the water control-treated grafts. Each skin graft in maintenance medium was degreased with 5 μL of alcohol for 3 hours after receipt in the laboratory. After 3 hours, all skin grafts were treated with the test items twice per day and incubated at 37°C ± 2°C, 5% CO2 for 1 or 5 days. System integrity was confirmed on days 1 and 5 using a viability control with MTT. Histology was performed by the Gredeco laboratory, and immunostaining for elastin and Ki67 was performed by the same laboratory. Immunostaining for filaggrin was performed by the Intertek laboratory. Detection of elastin (rabbit monoclonal antibody, clone PI5502, LSBio) was performed using a two-layer immunoperoxidase technique (ABC kit, Vector Laboratories) and demonstrated with AEC (3-amino-9-ethylcarbazole). The immunohistochemical staining intensity in elastic fibers was evaluated using a semiquantitative histological score. Epithelial proliferation was analyzed by immunohistochemistry using an anti-Ki67 antibody. Immunodetection was performed using the indirect immunoperoxidase technique 3-layer, amplified (DAKO kit) and revealed by AEC (3-amino-9-ethylcarbazole).The number of labeled cells (keratinocytes in the basal layer of the epidermis) is counted, providing the total number of basal cells and calculating the percentage of labeled cells. Specific staining of filaggrin is performed using immunoperoxidase staining (ABC kit, Fisher). The intensity of immunohistochemical markers in the epidermis is evaluated relative to the solvent negative control (water or DMSO 0.3%).

[0293] "Enriched in peptides having a molecular weight of less than 10 KD" as applied to the compositions of the present invention means that the dry weight % of peptides in the composition having a molecular weight of less than 10 KD is greater than the dry weight % of polypeptides / proteins in the composition having a molecular weight of 10 KD or more.

[0294] A "homologue" of a reference protein should be understood to mean a protein from a different species of plant that has at least 60% sequence homology with the reference protein. Thus, for example, homologues of the pea protein P13918 include: >gi|137584|sp|P08438.1|VCL_VICFA RecName:Full=Vicilin;Flags:Precursor[Vicia faba] >gi|22057|emb|CAA68559.1|Vicilin [Vicia faba var. minor]>gi|383931031|gb|AFH56916.1|Vicilin [Vicia faba] >gi|502105533|ref|XP_004492829.1|PREDICTED:Vicilin-like isoform X1 [Chickpea] Chickpea >gi|29539109|emb|CAD87730.1|Allergen Len c1.0101 [Lentil] Lentil Includes:

[0295] A "variant" of an anti-inflammatory fragment should be taken to mean a fragment having substantially the same amino acid sequence as the anti-inflammatory fragment and having anti-inflammatory activity as defined above. Thus, for example, the term should be taken to include fragments in which one or more amino acid residues have been altered. Preferably, such alterations include insertions, additions, deletions, and / or substitutions of five or fewer amino acids, more preferably four or fewer, even more preferably three or fewer, and most preferably only one or two amino acids. Insertions, additions, and substitutions using natural and modified amino acids are contemplated. The variant may have conservative amino acid changes, in which the introduced amino acid is structurally, chemically, or functionally similar to the one being replaced. Generally, the variant will have at least 70% amino acid sequence identity with the parent anti-inflammatory fragment, preferably at least 80% sequence identity, more preferably at least 90% sequence identity, and ideally at least 95%, 96%, 97%, 98%, or 99% sequence identity.

[0296] As used herein, the term "sequence identity" should be understood to include both sequence identity and similarity; i.e., a variant (or homolog) sharing 70% sequence identity with a reference sequence is one in which any 70% of the aligned residues of the variant (or homolog) are identical to or are conservative substitutions for corresponding residues in the reference sequence over the entire length of the sequence. Sequence identity is the amount of exactly corresponding characters between two different sequences. Consequently, gaps are not counted, and the measurement relates to the shorter of the two sequences. With respect to "sequence homology," this term should be understood to mean a variant (or homolog) that shares a defined similarity or percent identity with a reference sequence, provided that a percentage of the aligned residues of the variant (or homolog) are either identical to or are conservative substitutions for corresponding residues in the reference sequence, and the variant (or homolog) shares the same function as the reference sequence. This alignment and percent homology or sequence identity can be determined using software programs known in the art, for example, one alignment program is BLAST, using default parameters. Details of these programs can be found at the following internet address: http: / / www.ncbi.nlm.nih.gov / blast / Blast.cgi.

[0297] Variant of SEQ ID NO: 109 (anti-inflammatory peptide (I 37) Variants of SEQ ID NO: 109 (RGPQQYAEWQINEK) are provided below, including variants with 1, 2 or 3 conservative amino acid substitutions, 1, 2 to 3 non-conservative amino acid substitutions, 1-2 amino acid additions, and 1, 2 or 3 amino acid deletions: One conservative amino acid substitution: RGPQQYAEWQINER, RGPQQYAEWQINDK, RGPQQFAEWQINEK, KGPQQYAEWQINEK, RGPEQYAEWQINEK, RGPQEYAEWQINEK, RGPQQYADWQINEK, RGPQQYAEYQINEK (SEQ ID NOs: 268 to 275) Two conservative amino acid substitutions: KGPEQYAEWQINEK, KGPQEYAEWQINEK, KGPQQFAEWQINEK, RGPEQFAEWQINEK, KGPQQYAEWQINER, RGPQQYAEWQINDR, RGPQQYADWQINDK, RGPQQFAEWQINER (SEQ ID NOs: 276 to 283) Three conservative amino acid substitutions: RGPQQYAEWQVNEK, RGPQQFAEWQINEK, KGPQQFAEWQINER, KGPQQFAEWQVNEK, RGPQQFAEWQVNDK, RGPQQYADWQINDR, KGPQQYADWQINDK, RGPQQFADYQINEK (SEQ ID NOs: 284 to 291) One non-conservative amino acid substitution RGPQQYARWQINEK, RGPQQYAEWQINEE, HGPQQYAEWQINEK, RGPYQYAEWQINEK, RGPQQYMEWQINEK, RGPQQYAEWCINEK, RGPQPYAEWQINEK (SEQ ID NOs: 292 to 298) Two non-conservative amino acid substitutions RGGQQYAEWQINED, RGPQQYARWKINEK, RGGQQYAETQINEK, RGPLQYAEWQNNEK, EGPQQYAEWQINED, RGPQQYAEWQINLL, RGPQQGGEWQINEK (SEQ ID NOs: 299 to 305) Three non-conservative amino acid substitutions RGPQQYAEWQIGGG, RGPQQKYEWQINEK, RGPQAQYEWQINEK, RPHQQYAEWQINEK, RGPQHHHEWQINEK, RGPPQYAPPQINEK, RGPQCYYEWCINEK, RGPTQYAEGQINEG (SEQ ID NOs: 306 to 313) Addition of one or two amino acids RGPQQYAEWQINEKG, RGPQQYAEWQINEKY, RGPQQYAFTEWQINEK, RGPQSQYAEWQINEKPM, RGPQQYAEWQINEKKK, RRRRGPQQYAEWQINEK (SEQ ID NOs: 314 to 319).

[0298] The term "variant" generally encompasses fragments of the peptides of the invention. A "fragment of a peptide of the invention" or "peptide fragment" refers to a fragment of a peptide of the invention having at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22 amino acids and typically possessing biological activity, such as anti-inflammatory activity, cell growth or proliferation promoting activity, glucose transport promoting activity, or antibacterial activity. In one embodiment, the fragment consists of at least 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the reference sequence. Examples of fragments of the invention are provided in SEQ ID NOs: 320-330. RGPQQYAEWQINE, RGPQQYAEWQIN, RGPQQYAEWQI, GPQQYAEWQINEK, PQQYAEWQINEK, QQYAEWQINEK, QQYAEWQI, PQQYAEWQINE, PQQYAEWQIN, RGPQQYA, EWQINEK (SEQ ID NOs: 320 to 330) "Inflammatory disorder" refers to an immune-mediated inflammatory condition affecting humans and generally characterized by the dysregulated expression of one or more cytokines. Examples of inflammatory disorders include skin inflammatory disorders, joint inflammatory disorders, cardiovascular inflammatory disorders, certain autoimmune diseases, lung and airway inflammatory disorders, and intestinal inflammatory disorders. Examples of skin inflammatory disorders include dermatitis, such as atopic dermatitis and contact dermatitis, acne vulgaris, and psoriasis. Examples of joint inflammatory disorders include rheumatoid arthritis. Examples of cardiovascular inflammatory disorders include cardiovascular disease and atherosclerosis. Examples of autoimmune diseases include type 1 diabetes, Graves' disease, Guillain-Barré disease, lupus, psoriatic arthritis, and ulcerative colitis. Examples of lung and airway inflammatory disorders include asthma, cystic fibrosis, COPD, emphysema, and acute respiratory distress syndrome. Examples of intestinal inflammatory disorders include colitis and inflammatory bowel disease. Other inflammatory disorders include cancer, hay fever, periodontitis, allergies, hypersensitivity, ischemia, depression, systemic diseases, post-infectious inflammation and bronchitis.

[0299] As used herein, the term "metabolic disorder" shall be understood to include prediabetes, diabetes, type 1 diabetes, type 2 diabetes, metabolic syndrome, obesity, diabetic dyslipidemia, hyperlipidemia, hypertension, hypertriglyceridemia, hyperfattyacidemia, hypercholerterolemia, hyperinsulinemia and MODY.

[0300] "Artificial" as applied to edible products should be understood to mean made by humans and not occurring in nature.

[0301] "Maintaining or restoring intestinal health" refers to reducing and / or modulating pro-inflammatory responses in the intestine, more specifically, epithelial cells. A healthy microbiome provides some protection from pathogenic viruses and bacteria, and its presence is necessary to guide the development of our immune system. These bacteria can be manifested by inflammation, and as a result, they can respond to human signals of stress, illness, or age, turning on their pathogenic genes and causing or contributing to disease. Having the ability to reduce and maintain inflammatory responses at healthy levels can help maintain healthy bacteria. Digestive problems, including the number one health issue in North America, appear to be occurring more frequently in recent years. One way to maintain digestive health is to maintain appropriate inflammation and intestinal flora.

[0302] "Maintaining or restoring muscle health" means helping to maintain or restore muscle health in a mammal due to injury sustained during exercise. By reducing inflammation, the peptides promote recovery from injury during exercise and reduce muscle aches / pains and injuries associated with exercise. They can also be used to reduce and prevent muscle cramps, allowing for faster recovery from muscle cramps. Cramps can be caused by physical stress, mental stress, and / or repetitive strain-trauma stress. By reducing inflammation, the peptides help to reduce muscle myopathy, help prevent sarcopenia in mammals, promote recovery from injury during exercise, and reduce muscle aches / pains and injuries associated with exercise. They can also be used to reduce and prevent muscle cramps, allowing for faster recovery from muscle cramps. Cramps can be caused by physical stress, mental stress, and / or repetitive strain-trauma stress. By reducing inflammation, the peptides help to reduce muscle myopathy, helping to prevent sarcopenia in mammals.

[0303] As used herein, the term "composition" should be understood to mean something made by the hand of man, and does not exclude naturally occurring compositions. Exemplary compositions include foods, beverages, dietary supplements, personal care compositions, and pharmaceutical compositions.

[0304] As used herein, the term "substantially all" as applied to a list of peptides or fragments shall be understood to mean at least 60%, 70%, 80%, 90% or 95% of the peptides or fragments.

[0305] As used herein, the term "personal care composition" should be understood to mean a composition formulated for human use in cleansing or treating the human body, particularly the skin, teeth, nails, feet, and hair. Examples include shampoos, conditioners, skin creams and lotions, powders, dentifrices, shower gels or creams, body lotions, deodorants, and antiperspirants.

[0306] As used herein, the term "dietary supplement" should be understood to mean a product formulated for oral ingestion by a mammal and intended to provide a health benefit to the recipient. Dietary supplements can take any form, such as solid, liquid, or powder. Examples of dietary supplements include powders, tablets, capsules, and drinks. [Brief explanation of the drawings]

[0307] [Figure 1] Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 2] Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 3] Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 4]Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 5] Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 6] Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 7] Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 8] Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 9]Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 10] Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 11] Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 12] Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 13] Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 14]Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 15] Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 16] Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 17] Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 18] Figure 1 shows the effect of 18 synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 19]Figure 1 shows the viability of J774.2 macrophages after treatment with synthetic peptides. J774.2 macrophages were treated with 100 μM of synthetic peptide for 24 hours, after which an Alamar Blue assay was performed. Data are shown as the mean of n=3 + / - SEM. [Figure 20] Figure 1 shows the effect of peptide compositions on cell viability. J774.2 macrophages were treated with (A) 1 mg / ml or (B) 0.5 mg / ml of peptide compositions for 24 hours, followed by Alamar Blue assay. Data are shown as (A) n = 1 + / - SEM and (B) n = 3 + / - SEM. [Figure 21] Figure 1 shows the effect of DMSO vehicle on TNFα and IL-1β secretion from J774.2 macrophages. J774.2 macrophages were treated with 0.3% and 1% final concentrations of DMSO (equivalent to the amount used to dissolve the peptide) for 24 hours to establish the effect on TNFα and IL-1β secretion after stimulation. Data are shown as mean of n=3 + / - SEM (***p<0.001 for LPS). [Figure 22] Figure 1 shows the effect of six peptides of the present invention on TNFα and IL-1β secretion from J774.2 macrophages. J774.2 macrophages were treated with 100 μM of synthetic peptide for 24 hours and then stimulated with (A) LPS (10 ng / ml) for 5 hours or (B) LPS (10 ng / ml) for 5 hours followed by ATP (5 mM) for 1 hour. Supernatants were collected, and levels of (A) TNFα and (B) IL-1β were determined by ELISA. (***p<0.001 for LPS, **p<0.01 for LPS, *p<0.05 for LPS / ATP, ###p<0.001 for LPS / ATP, ##p<0.01 for LPS / ATP, and #p<0.05 for LPS / ATP). Final concentrations of DMSO in the wells: SP1 - 0.3%, SP2 - 0%, SP3 - 0.3%, SP4 - 1%, SP5 - 1%, SP6 - 0.3%, positive control - 0%. Data are shown as the mean of n=3 + / - SEM. [Figure 23]

[0033] Figure 1 shows the effect of peptide compositions of the present invention on TNFα and IL-1β secretion. J774.2 macrophages were treated with 0.5 mg / ml of peptide composition for 24 hours and then stimulated with (A) LPS (10 ng / ml) for 5 hours or (B) LPS (10 ng / ml) for 5 hours followed by ATP (5 mM) for 1 hour. Supernatants were collected, and levels of (A) TNFα and (B) IL-1β were determined by ELISA. (***p<0.001 for untreated + LPS, ###p<0.001 for untreated + LPS / ATP). Data are presented as mean, n=3 + / - SEM. [Figure 24] Figure 1 shows the effects of synthetic peptides and DMSO vehicle on TNFα. J774.2 macrophages were treated with 100 μM synthetic peptide for 24 hours, followed by LPS (10 ng / ml) for 5 hours. Supernatants were collected, and TNFα levels were determined by ELISA. (###p<0.001 for 0.3% DMSO + LPS, ##p<0.01 for 0.3% DMSO + LPS, +++p<0.001 for 1% DMSO + LPS, ++p<0.01 for 1% DMSO + LPS / ATP). Final concentrations of DMSO in wells: positive control - 0%, SP1 - 0.3%, SP2 - 0%, SP3 - 0.3%, SP4 - 1%, SP5 - 1%, SP6 - 0.3%. [Figure 25] THP-1 differentiated macrophages treated with the rice peptide (I_2_HR) composition of the present invention for 24 hours prior to LPS stimulation were compared with untreated cells. TNF-α secretion in I_2_HR-treated cells was reduced by 92% compared to untreated cells. Significant results demonstrating the efficacy of I_2_HR were observed at concentrations of 100 μg / ml and 500 μg / ml. [Figure 26] Figure 1 shows the effect of three synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 27] Figure 1 shows the effect of three synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). [Figure 28] Figure 1 shows the effect of three synthetic peptides of the present invention on TNF secretion in THP1 cells. All experiments were performed in duplicate on three plates (6 wells per condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control). DETAILED DESCRIPTION OF THE INVENTION

[0308] Detailed Description of the Invention [Example]

[0309] Inflammatory response TNF-α is secreted by macrophages in response to stimulation with endotoxins such as lipopolysaccharide (LPS). TNF-α is thought to be involved in systemic inflammation, and dysregulation of TNF-α production is thought to be involved in numerous diseases. The Biolegend assay is a sandwich ELISA kit designed for accurate quantification of human TNF-α from cell culture supernatants, serum, or plasma.

[0310] THP-1 monocytes were seeded at 10,000 cells per well in 96-well plates in RPMI containing 10% fetal calf serum (FCS), 1% Pen / strep, 1% L-glutamine, 100 nM PMA, and allowed to differentiate for 72 hours prior to the experiment.

[0311] After differentiation, the cells were incubated with 100 ng / ml, 10 ng / ml, or 1 ng / ml of synthetic peptides, respectively, for 24 hours.

[0312] After treatment, cells were stimulated with 10 ng / ml LPS for 5 h, and the amount of TNF-α in the supernatant was determined using a Biolegend assay ELISA kit.

[0313] Results were calculated as a percentage of the untreated control. An increase in optical density reading indicates a greater release of TNF-α into the cell culture supernatant.

[0314] The results are provided in Figures 1-21 and summarized in Table 1 below. All experiments were set up in duplicate on three plates (6 wells / condition). Significance was calculated using Student's t-test (*p<0.05 compared to control, **p<0.01 compared to control, ***p<0.001 compared to control).

[0315] [Table 1] [Example]

[0316] Inflammatory response The effects of six synthetic peptides of the present invention, SP1 to SP6 (SEQ ID NOs: 108, 109, 110, 111, 85 and 91) and four peptide compositions on inflammatory responses in vitro using cell lines were determined.

[0317] Peptide composition I_1_HR (Rice) contained the following peptides (identified by SEQ ID NOs: 116, 197, 207, 112, 211, 158, 201, 203, 114, 183, 130, 113, 182, 167, 166, 152, 220, 213, 215, 154, 219, 218, 165, 123, 185, 190, 209, 181, 198, 200, 147, 172, 184, 124, 153, 205, 115, 196, 151, 161, 160, 216, 210, 208, 146, 133, 204, 212, 206.

[0318] Peptide composition I_2_HR (Rice) contained the following peptides (identified by SEQ ID NOs: 189, 177, 174, 129, 176, 202, 193, 195, 194, 192, 182, 128, 220, 127, 134, 136, 135, 180, 179, 178, 219, 218, 145, 120, 175, 190, 149, 126, 187, 191, 121, 122, 159, 132, 162, 137, 150, 186, 188, 164, 118, 125, 163, 157, 156, 117.

[0319] Peptide composition E_1_HR (pea) contained the following peptides (identified by SEQ ID NOs: 74, 76, 106, 102, 101, 100, 92, 96, 83, 89, 90, 104, 82, 75, 79, 78, 77, 99, 103, 72, 86, 105, 94, 93, 81, 97, 80, 88, 85, 87, 71, 107, 73, 84, 98, 95.

[0320] The peptide composition E_2_HR contained homologues of the peptides of the invention.

[0321] The J774.2 murine macrophage cell line was treated with 100 μM of each synthetic peptide (SP) and 0.5 mg / ml of each peptide composition, and the effects on two pro-inflammatory markers—tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β)—were determined after inflammation was induced using lipopolysaccharide (LPS) as the inflammatory stimulus. One-way analysis of variance with Dunnett's test for multiple comparisons, comparing all means to a single control mean, was used. [Example]

[0322] Synthetic peptides: cell viability Synthetic peptides were first diluted in a suitable solvent. Dimethyl sulfoxide (DMSO) was the solvent of choice for peptides with predicted low aqueous solubility. The final DMSO concentrations in each well were: SP1 (1,155 HR) - 0.3%, SP2 (1,374 HR) - 0%, SP3 (E,155 HR) - 0.3%, SP4 (E,54 HR) - 1%, SP5 (E,41 HR) - 1%, SP6 (E,788 HR) - 0.3%, and positive control - 0%. Cells were first treated with 100 μM of each SP for 24 hours, after which an Alamar Blue assay was performed. No viability issues were observed with any of the peptides. [Example]

[0323] Peptide compositions: preparation and toxicity Peptide compositions were prepared by adjusting the pH to between 6 and 7 and sterile filtering. The effect of the peptide compositions on cell viability was determined. J774.2 macrophages were treated with 1 mg / ml and 0.5 mg / ml of each peptide composition, hydrogen peroxide to induce cell death as a positive control, and a peptide known to be nontoxic as a negative control. An Alamar Blue assay was then performed, and cell viability is shown in Figure 19 as a percentage of untreated (100%). Because cell viability was impaired when 1 mg / ml of peptide was used, 0.5 mg / ml of the peptide composition was used for further assays. [Example]

[0324] Inflammatory markers The effect of DMSO on TNFα and IL-1β secretion was determined. 1% DMSO significantly increased the levels of TNFα (Figure 3A. ***p<0.001 relative to LPS), which was taken into account when analyzing the effect of peptides on TNFα. No significant effect was observed on DMSO and IL-1β secretion. [Example]

[0325] Inflammatory response THP-1 differentiated macrophages were treated with the rice peptide (I_2_HR) composition of the present invention for 24 hours prior to LPS stimulation and compared with untreated cells. TNF-α secretion in I_2_HR-treated cells was reduced by 92% compared to untreated cells. Significant results demonstrating the efficacy of I_2_HR were observed at concentrations of 100 μg / ml and 500 μg / ml.

[0326] The present invention is not limited to the embodiments described hereinabove, which may be varied in arrangement and detail without departing from the spirit of the present invention.

[0327] Sequence information Pea Protein 1: P13918 - 1 - MAATTMKASFPLLMGISFLASVCVSSRSDPQNPFIFKSNKFQTLFENENGHIRLLQKFDQRSKIFENLQNYRLLEYKSKPHTIFLPQHTDADYILVVLSGKAILTVLKPDDR NSFNLERGDTIKLPAGTIAYLVNRDDNEELRVLDLAIPVNRPGQLQSFLLSGNQNQQNYLSGFSKNILEASFNTDYEEIEKVLLEEHEKETQHRRSLKDKRQQSQEENVIVKLSR GQIEELSKNAKSTSKKSVSSESEPFNLRSRGPIYSNEFGKFFEITPEKNPQLQDLDIFVNSVEIKEGSLLLPHYNSRAIVIVTVNEGKGDFELVGQRNENQQEQRKEDDEEEEQG EEEINKQVQNYKAKLSSGDVFVIPAGHPVAVKASSNLDLLGFGINAENNQRNFLAGDEDNVISQIQRPVKELAFPGSAQEVDRILENQKQSHFADAQPQQRERGSRETRDRLSSV [SEQ ID 1] Area: 253 to 274 - PFNLRSRGPIYSNEFGKFFEIT [SEQ ID 17] Peptide: SRGPIYSNEFGK [SEQ ID 71] Area: 110 to 126 - KPDDRNSFNLERGDTIK [SEQ ID 18 ] Peptide: NSFNLER [SEQ ID 72] Area: 134 to 160 - YLVNRDDNEELRVLDLAIPVNRPGQLQ [SEQ ID 19] Peptide: VLDLAIPVNR [SEQ ID 73] Peptide: DDNEELR [SEQ ID 74] Area: 331 to 381 - QEQRKEDDEEEEQGEEEINKQVQNYKAKLSSGDVFVIPAGHPVAVKASSNL [SEQ ID 20] Peptide: LSSGDVFVIPAGHPVAVK [SEQ ID 75] Peptide: EDDEEEEQGEEEINK [SEQ ID 76] Area: 175 to 242 - SGFSKNILEASFNTDYEEIEKVLLEEHEKETQHRRSLKDKRQQSQEENVIVKLSRGQIEELSKNAKST [SEQ ID 21] Peptide: NILEASFNTDYEEIEKVLLEEHEKETQHR [SEQ ID 77] Peptide: NILEASFNTDYEEIEKVLLEEHEK [SEQ ID 78] Peptide: NILEASFNTDYEEIEK [SEQ ID 79] Peptide: RQQSQEENVIVK [SEQ ID 80] Peptide: QQSQEENVIVK [SEQ ID 81] Peptide: LSRGQIEELSK [SEQ ID 82] Peptide: GQIEELSK [SEQ ID 83] Peptide: VLLEEHEK [SEQ ID 84] Area: 35 to 108 - PFIFKSNKFQTLFENENGHIRLLQKFDQRSKIFENLQNYRLLEYKSKPHTIFLPQHTDADYILVVLSGKAILTV [SEQ ID 22] Peptide: SKPHTIFLPQHTDADYILVVLSGK [SEQ ID 85] Peptide: PHTIFLPQHTDADYILVVLSGK [SEQ ID 86] Peptide: SNKFQTLFENENGHIR [SEQ ID 87] Peptide: SKIFENLQNYR [SEQ ID 88] Peptide: IFENLQNYR [SEQ ID 89] Area: 423 to 450 - QEVDRILENQKQSHFADAQPQQRERGSR [SEQ ID 23] Peptide: ILENQKQSHFADAQPQQR [SEQ ID 90] Peptide PGQLQSFLLSGNQNQQNYLSGFSK [SEQ ID 91]

[0328] Pea Protein 2: P02856 - 2 - DRRQELSNENVLVKVSRRQLEELSKNAKSSSRRSVSSESGPFNLRSEDPLYSNNSGKFFELTPEKNQQLQDLDLFVNSVDLKEGSLLLPNYNSRALLVLVLVVNEGKGDFELVGQRNENQGKEN [SEQ ID 2] Area: 53 to 87 - NNSGKFFELTPEKNQQLQDLDLFVNSVDLKEGSLL [SEQ ID 24] Peptide: FFELTPEKNQQLQDLDLFVNSVDLK [SEQ ID 92] Area: 14 to 30 - KVSRRQLEELSKNAKSS [SEQ ID 25] Peptide: QLEELSK [SEQ ID 93]

[0329] Pea Protein 3: P15838 - 3 - MATKLLALSLSFCFLLLGGCFALREQPEQNECQLERLNALEPDNRIESEGGLIETWNPNNKQFRCAGVALSRATLQHNALRRPYYSNAPQEIFIQQGNGYFGMVFPGCPETFEEPQESEQGEGRRYRDRH QKVNRFREGDIIAVPTGIVFWMYNDQDTPVIAVSLTDIRSSNNQLDQMPRRFYLAGNHEQEFLRYQHQQGGKQEQENEGNNIFSGFKRDFLEDAFNVNRHIVDRLQGRNEDEEKGAIVKVKGGLSIISPP EKQARHQRGSRQEEEDEDEERQPRHQRGSRQEEEDEDEERQPRHQRRRGEEEEEDKKERRGSQKGKSRRQGDNGLEETVCTAKLRLNIGPSSSPDIYNPEAGRIKTVTSLDLPVLRWLKLSAEHGSLH KNAMFVPHYNLNANSIIYALKGRARLQVVNCNGNTVFDGELEAGRALTVPQNYAVAAKSLSDRFSYVAFKTNDRAGIARLAGTSSVINNLPLDVVAATFNLQRNEARQLKSNNPFKFLVPARQSENRASA [SEQ ID 3] Area: 267 to 287 - QRGSRQEEDEDEDEERQPRHQ [SEQ ID 26] Peptide: QEEDEDEDEER [SEQ ID 94] Area: 190 to 222 - QEFLRYQHQQGGKQEQENEGNNIFSGFKRDFLE [SEQ ID 27] Peptide: YQHQQGGKQEQENEGNNIFSGFK [SEQ ID 95]

[0330] Pea protein 4: Q9M3X6 - 4 - MATTIKSRFPLLLLGIIFLASVVCVTYANYDEGSEPRWPAQRERGRQEGEKEEKRHGEWRPSYEKEEDEEEGQRERRQEGEKREEKRHGEWRPSYEKQEDEEEKQKYRYQREKEDEEEKQKYQYQREKKEQKEVQPGRERWEREEDEEQVDE EWRGSQRREDPEERARLRHREERTKRDRRHQREGEEEERSSESQERRNPFLFKSNKFLTLFENENGHIRLLQRFDKRSDLFENLQNYRLVEYRAKPHTIFLPQHIDADLILVVLSGKAILTVLSPNDRNSYNLERGDTIKLPAGTTSYLVNQD DEEDLRLVDLVIPVNGPGKFEAFDLAKNKNQYLRGFSKNILEASYNTRYETIEKVLLEEQEKDRKRRQQGEETDAIVKVSREQIEELKKLAKSSSSKKSLPSEFEPINLRSHKPEYSNKFGKLFEITPEKKKYPQLQDLDLFVSCVEINEGALMLPHYNSRAIVVLLVNEGKGNLELLGLKNEQQEREDRKERNNEVQRYEARLSPGDVVIIPAGHPVAITASSNLNLLGFGINAENNERNFLSGSDDNVISQIENPVKELTFPGSVQEINRLIKNQKQSHFANAEPEQKEQGSQGKRSPLSSILGTFY [SEQ ID 4] Region : 284 to 317 - YNLERGDTIKLPAGTTSYLVNQDDEEDLRLVDLV [SEQ ID 28] peptide : GDTIKLPAGTTSYLVNQDDEEDLR [SEQ ID 96] Region : 321 to 400 - NGPGKFEAFDLAKNKNQYLRGFSKNILEASYNTRYETIEKVLLEEQEKDRKRRQQGEETDAIVKVSREQIEELKKLAKSS [SEQ ID 29] peptide : RQQGEETDAIVK [SEQ ID 97] peptide : VLLEEQEKDRK [SEQ ID 98] Peptide: NILEASYNTR [SEQ ID 99] Peptide: FEAFDLAK [SEQ ID 100] Peptide: EQIEELKK [SEQ ID 101] Peptide: EQIEELK [SEQ ID 102] Peptide: NKNQYLR [SEQ ID 103] Area: 503 to 549 - RYEARLSPGDVVIIPAGHPVAITASSNLNLLGFGINAENNERNFLSG [SEQ ID 30] Peptide: LSPGDVVIIPAGHPVAITASSNLNLLGFGINAENNER [SEQ ID 104] Area: 89 to 112 - HGEWRPSYEKQEDEEEKQKYRYQR [SEQ ID 31] Peptide: PSYEKQEDEEEKQK [SEQ ID 105] Region: 62 to 80 - PSYEKEEDEEEGQRERGRQ [SEQ ID 32] Peptide: EEDEEEGQR [SEQ ID 106]

[0331] Pea protein 5: D3VNE1-5- MAATPIKPLMLLAIAFLASVCVSSRSDQENPFIFKSNRFQTLYENENGHIRLLQKFDKRSKIFENLQNYRLLEYKSKPRTLFLPQYTDADFILVVLSGKATLTVLKSNDRNSFNLERGDTIKLPAGTIAYLANRDDNEDLRVLDLTIPVNKPGQLQSFLLSGTQNQPSLLSGFSKNILEAAFNTNYEEIEKVLLEQQEQEPQHRRSLKDRRQEINEENVIVKVSREQIEELSKNAKSSSSKKSVSSESGPFNLRSRNPIYSNKFGKFFEITPEKNQQLQDLDIFVNSVDIKEGSLLLPNYNSRAIVIVTVTEGKGDFELVGQRNENQGKENDKEEEQEEETSKQVQLYRAKLSPGDVFVIPAGHPVAINSASSDLNIGFGINAENNERNFLAGEEDNVISQVERPVKELAFPGSSHEVDRLLKNQKQSYFANAQPLQRE [SEQ ID 5] Region : 75 to 104 - KSKPRTLFLPQYTDADFILVVLSGKATLTV [SEQ ID 33] peptide : TLFLPQYTDADFILVVLSGK [SEQ ID 107]

[0332] イネprotein 7: Q6K508 MATTTSLLSSCLCALLLAPLFSQGVDAWESRQGASRQCRFDRLQAFEPLRKVRSEAGDTE YFDERNEQFRCAGVFVIRRVIEPQGLVVPRYSNTPALAYIIQGKGYVGLTFPGCPATHQQ QFQLFEQRQSDQAHKFRDEHQKIHEFRQGDVVALPASVAHWFYNGGDTPAVVVYVYDIKS FANQLEPRQKEFLLAGNNQRGQQIFEHSIFQHSGQNIFSGFNTEVLSEALGINTEASKRL QSQNDQRGDIIRVKHGLQLLKPTLTQRQEEHRQYQQVQYREGQYNGLDENFCTIKARVNI ENPSRADYYNPRAGRITLLNNQKFPILNLIGMGAARVNLYQNALLSPFWNINAHSVVYII QGSVRVQVANNQGRSVFNGVLHQGQLLIIPQNHAVIKKAEHNGCQYVAIKTISDPTVSWV AGKNSILRALPVDVIANAYRISRDEARRLKNNRADEIGPFTPRFPQKSQRGYQFLTEGLS LIGM [SEQ ID 6] Peptide: GYVGLTFPGCPATHQQQFQLFEQR [SEQ ID 108]

[0333] イネprotein 8: Q6K7K6 MASMSTILPLCLGLLLFFQVSMAQFSFGGSPLQSPRGFRGDQDSRHQCRFEHLTALEATH QQRSEAGFTEYYNIEARNEFRCAGVSVRRLVVESKGLVLPMYANAHKLVYIVQGRGVFGM ALPGCPETFQSVRSPFEQEVATAGAEQSSIQKMRDEHQQLHQFHQGDVIAVPAGVAHWLY NNGDSPVVAFTVIDTSNNANQLDPKREFLAGGKPRSSWQQQSYSYQTEQLSRNQNIFAG FSPDLLSEALSVSKQTVLRLQGLSDPRGAIIRVENGLQALQPSLQVEPVKEEQTQAYLPT KQLQPTWLRSGGACGQQNVLDEIMCAFKLRKNIDNPQSSDIFNPHGGRITRANSQNFPIL NIIQMSATRIVLQNNALLTPHWTVNAHTVMYVTAGQGHIQVVDHRGRSVFDGELHQQQIL LIPQNFAVVVKARREGFAWVSFKTNHNAVDSQIAGKASILRALPVDVVANAYRLSREDSR HVKFNRGDEMAVFAPRRGPQQYAEWQINEK [SEQ ID 7] Peptide: RGPQQYAEWQINEK [SEQ ID 109]

[0334] Pea Protein 6: P13919 MATTIKSRFPLLLLLGIIFLASVVSVTYANYDEGSEPRVPAQRERGRQEGEKEEKRHGEW RPSYEKEEDEEEGQRERGRQEGEKEEKRHGEWGPSYEKQEDEEEKQKYRYQREKEDEEEK QKYQYQREKKEQKEVQPGRERWEREEDEEQVDEEWRGSQRREDPEERARLRHREERTKRD RRHQREGEEEERSSESQERRNPFLFKSNKFLTLFENENGHIRLLQRFDKRSDLFENLQNY RLVEYRAKPHTIFLPQHIDADLILVVLSGKAILTVLSPNDRNSYNLERGDTIKLPAGTTS YLVNQDDEEDLRLVDLVIPVNGPGKFEAFDLAKNKNQYLRGFSKNILEASYNTRYETIEK VLLEEQEKDRKRRQQGEETDAIVKVS [SEQ ID 8] Peptide: LVDLVIPVNGPGKFEAFDLAK [SEQ ID 110]

[0335] Pea Protein 7: P02855 MATTIKSRFPLLLLLGIIFLASVVSVTYANYDEGSEPRVPAQRERGRQEGEKEEKRHGEW RPSYEKEEDEEEGQRERGRQEGEKEEKRHGEWGPSYEKQEDEEEKQKYRYQREKEDEEEK QKYQYQREKKEQKEVQPGRERWEREEDEEQVDEEWRGSQRREDPEERARLRHREERTKRD RRHQREGEEEERSSESQERRNPFLFKSNKFLTLFENENGHIRLLQRFDKRSDLFENLQNY RLVEYRAKPHTIFLPQHIDADLILVVLSGKAILTVLSPNDRNSYNLERGDTIKLPAGTTS YLVNQDDEEDLRLVDLVIPVNGPGKFEAFDLAKNKNQYLRGFSKNILEASYNTRYETIEK VLLEEQEKDRKRRQQGEETDAIVKVS [SEQ ID 9] Peptide: KNPQLQDLDIFVNYVEIK [SEQ ID 111]

[0336] イネprotein 1 : P14323 - 1 - MASSVFSRFSIYFCVLLLCHGSMAQLFNPSTNPWHSPRQGSFRECRFDRLQAFEPLRKVRSEAGVTEYFDEKNELFQCTGTFVIRRVIQPQGLLVPRYTNIPGVVYIIQGRGSMGLTFPGCPATYQQQFQQFSSQGQSQKFRDEHQKIHQFRQGDIVALPAGVAHWFYNDGDAPIVAVYVYDVNANQLEPRQKEFLLAGNNNRAQQQQVYGSSIEQHSGQNIFSGFGVEMLSEALGINAVAAKRL QSQNDQRGEIIHVKNGLQLLKPTLTQQQEQAQAQDQYQQVQYSERQQTSSRWNGLEENFCTIKVRVNIENPSRADSYNPRAGRITSVNSQKFPILNLIQMSATRVNLYQNAILSPFWNVNAHSLV YMIQGRSRVQVVSNFGKTVFDGVLRPGQLLIIPQHYAVLKKAEREGCQYIAIKTNANAFVSHLAGKNSVFRALPVDVVANAYRISREQARSLKNNRGEEHGAFTPRFQQQYYPGLSNESESSETE [SEQ ID NO:10] Region : 138 to 159 - SQSQKFRDEHQKIHQFRQGDIV [SEQ ID 34] peptide : DEHQKIHQFR [SEQ ID 112] peptide : FRDEHQK [SEQ ID 113] Region: 336 to 358 - VNSQKFPILNLIQMSATRVNLYQ [SEQ ID 35] Peptide: FPILNLIQMSATR [SEQ ID 114] Area: 423 to 462 - YIAIKTNANAFVSHLAGKNSVFRALPVDVVANAYRISREQ [SEQ ID 36] Peptide: TNANAFVSHLAGK [SEQ ID 115] Peptide: ALPVDVVANAYR [SEQ ID 116] Area: 175 to 205 - APIVAVYVYDVNNNANQLEPRQKEFLLAGNN [SEQ ID 37] Peptide: YVYDVNNNANQLEPRQKEFL [SEQ ID 117] Peptide: VYVYDVNNNANQLEPRQKEFL [SEQ ID 118] Area: 318 to 334 - ENPSRADSYNPRAGRIT [SEQ ID 38] Peptide: ADSYNPR [SEQ ID 119] Area: 265 to 296 - GLQLLKPTLTQQEQAQAQDQYQQVQYSERQQ [SEQ ID 39] Peptide: KPTLTQQQEQAQAQDQ [SEQ ID 120] Peptide: QAQAQDQYQQVQY [SEQ ID 121] Peptide: QAQDQYQQVQY [SEQ ID 122] Region: 45 to 62 - CRFDRLQAFEPLRKVRSE [SEQ ID 40] Peptide: LQAFEPLR [SEQ ID 123] Area: 361 to 408 - ILSPFWNVNAHSLVYMIQGRSRVQVVSNFGKTVFDGVLRPGQLLIIPQ [SEQ ID 41] Peptide: SRVQVVSNFGK [SEQ ID 124] Peptide: WNVNAHSLVY [SEQ ID 125] Peptide: NVNAHSLVY [SEQ ID 126] Peptide: IQGRSRVQVVSNFGK [SEQ ID 127] Peptide: GKTVFDGVLRPGQL [SEQ ID 128] Peptide: FGKTVFDGVLRPGQL [SEQ ID 129] Area: 476 to 499 - AFTPRFQQQYYPGLSNESESETSE [SEQ ID 42] Peptide: FQQQYYPGLSNESESETSE [SEQ ID 130] Peptide: QQYYPGLSN [SEQ ID 131] Peptide: QQQYYPGLSN [SEQ ID 132]

[0337] Rice Protein 2: P07728 - 2 - MASINRPIVFFTVCLFLLCNGSLAQQLLGQSTSQWQSSRRGSPRECRFDRLQAFEPIRSVRSQAGTTEFFDVSNEQFQCTGVSVVRRVIEPRGLLLPHYTNGASLVYIIQGRGITGPTFPGCPESYQQQFQQSGQAQLTESQSQSQKFKDEHQKIHRFRQGDVIALPAGVAHWCYNDGEVPVVAIYVTDLNNGANQLDPRQRDFLLAGNKRNPQAYRREVEERSQNIFSGFSTELLSEALGVSSQVARQLQCQNDQRGEIVRVEHGLSLLQPYASLQEQEQGQVQSRERYQEGQYQQSQYGSGCSNGLDETFCTLRVRQNIDNPNRADTYNPRAGRVTNLNTQNFPILSLVQMSAVKVNLYQNALLSPFWNINAHSVVYITQGRARVQVVNNNGKTVFNGELRRGQLLIIPQHYAVVKKAQREGCAYIAFKTNPNSMVSHIAGKSSIFRALPNDVLANAYRISREEAQRLKHNRGDEFGAFTPIQYKSYQDVYNAAESS [SEQ ID 11] Region: 332 to 362 - PRAGRVTNLNTQNFPILSLVQMSAVKVNLYQ [SEQ ID 43] Peptide: VTNLNTQNFPILSLVQMSAVK [SEQ ID 133] Region: 375 to 406 - HSVVYITQGRARVQVVNNNGKTVFNGELRRGQ [SEQ ID 44] Peptide: ITQGRARVQVVNNNGKTVF [SEQ ID 134] Peptide: ITQGRARVQVVNNNGKTVFNGE [SEQ ID 135] Peptide: ITQGRARVQVVNNNGKTVFNG [SEQ ID 136] Peptide: RVQVVNNNGKTVF [SEQ ID 137] Region: 440 to 471 - HIAGKSSIFRALPNDVLANAYRISREEAQRLK [SEQ ID 45] Peptide: RALPNDVLANAYRISREE [SEQ ID 138] Peptide: SIFRALPNDVLANAYR [SEQ ID 139] Peptide: SIFRALPNDVLANAY [SEQ ID 140] Peptide: SIFRALPNDVLAN [SEQ ID 141] Peptide: SSIFRALPNDVLANAYR [SEQ ID 142] Peptide: SIFRALPNDVLANAYRISREE [SEQ ID 143] Peptide: SIFRALPND [SEQ ID 144] Area: 180 to 208 - VPVVAIYVTDLNNGANQLDPRQRDFLLAG [SEQ ID 46] Peptide: IYVTDLNNGANQLDPRQRD [SEQ ID 145]

[0338] Rice Protein 3: P07730 - 2 - MASINRPIVFFTVCLFLLCDGGSLAQQLLGQSTSQWQSSRRGSPRGCRFDRLQAFEPIRSVRSQAGTTEFFDVSNELFQCTGVSVVRRVIEEPRGLLLPHYTNGASLVYIIQGRGITGPTFPGCPE TYQQQFQQSGQAQLTESQSQSHKFKDEHQKIHRFRQGDVIALPAGVAHWCYNDGEVPVVAIYVTDINNGANQLDPRQRDFLLAGNKRNPQAYRREVEEWSQNIFSGFSTELLSEAFGISNQVARQ LQCQNDQRGEIVRVERGLSLLQPYASLQEQEQGQMQSREHYQEGGYQQSQYGSGCPNGLDETFCTMRVRQNIDNPNRADTYNPRAGRVTNLNSQNFPILNLVQMSAVKVNLYQNALLSPFWNINA HSIVYITQGRAQVQVVNNNGKTVFNGELRRGQLLIVPQHYVVVKKAQREGCAYIAFKTNPNSMVSHIAGKSSIFRALPTDVLANAYRISREEAQRLKHNRGDEFGAFTPLQYKSYQDVYNVAESS [SEQ ID 12] Area: 311 to 362 - TFCTMRVRQNIDNPNRADTYNPRAGRVTNLNSQNFPILNLVQMSAVKVNLYQ [SEQ ID 47] Peptide: VTNLNSQNFPILNLVQMSAVK [SEQ ID 146] Peptide: QNIDNPNR [SEQ ID 147] Peptide: ADTYNPR [SEQ ID 148] Peptide: NIDNPNRADTYNPRAGRVTNL [SEQ ID 149] Peptide: RVRQNIDNPNRADTYNPRAGRVTNL [SEQ ID 150] Area: 427 to 499 - YIAFKTNPNSMVSHIAGKSSIFRALPTDVLANAYRISREEAQRLKHNRGDEFGAFTPLQYKSYQDVYNVAESS[SEQ ID 48] Peptide: TNPNSMVSHIAGKSSIFR [SEQ ID 151] Peptide: HNRGDEFGAFTPLQYK [SEQ ID 152] Peptide: SYQDVYNVAESS [SEQ ID 153] Peptide: ISREEAQR [SEQ ID 154] Peptide: SIFRALPTDVLANAYRISREE [SEQ ID 155] Peptide: YRISREEAQRLKHNRGDEF [SEQ ID 156] Peptide: YRISREEAQRLKHNRGDE [SEQ ID 157] Area: 143 to 178 - SQSHKFKDEHQKIHRFRQGDVIALPAGVAHWCYNDG [SEQ ID 49] Peptide: FKDEHQKIHR [SEQ ID 158] Peptide: QGDVIALPAGVAHW [SEQ ID 159] Area: 381 to 409 - TQGRAQVQVVNNNGKTVFNGELRRGQLLI [SEQ ID 50] Peptide: TVFNGELRR [SEQ ID 160] Peptide: TVFNGELR [SEQ ID 161] Peptide: QVQVVNNNGKTVF [SEQ ID 162] Area: 101 to 124 - NGASLVYIIQGRGITGPTFPGCPE [SEQ ID 51] Peptide: YIIQGRGITGPTF [SEQ ID 163] Peptide: VYIIQGRGITGPTF [SEQ ID 164] Region: 46 to 66 - CRFDRLQAFEPIRSVRSQAGT [SEQ ID 52] Peptide: LQAFEPIRSVR [SEQ ID 165] Area: 253 to 292 - QNDQRGEIVRVERGLSLLQPYASLQEQEQGQMQSREHYQE [SEQ ID 53] Peptide: GLSLLQPYASLQEQEQGQMQSR [SEQ ID 166] Peptide: GEIVRVER [SEQ ID 167] Peptide: RGLSLLQPYASLQ [SEQ ID 168] Peptide: RGLSLLQPYASLQEQ [SEQ ID 169] Peptide: RGLSLLQPYASLQEQE [SEQ ID 170] Peptide: RGLSLLQPYASLQE [SEQ ID 171] Area: 199 to 233 - PRQRDFLLAGNKRNPQAYRREVEEWSQNIFSGFST [SEQ ID 54] Peptide: RNPQAYR [SEQ ID 172] Peptide: FLLAGNKRNPQAY [SEQ ID 173] Peptide: EVEEWSQNIF [SEQ ID 174] Peptide: LAGNKRNPQAYR [SEQ ID 175] Peptide: FLLAGNKRNPQA [SEQ ID 176]

[0339] Rice Protein 4: Q0D7S0 - 3 - MASNKVVFSVLLLAVVSVLAATATMAEYHHQDQVVYTPGPLCQPGMGYPMYPLPRCRALVKRQCVGRGTAAAAEQVRRDCRQLAAVDDSWCRCEAISHMLGGIYRELGAPDVGHPMSEVFRGCRRGDLERAAASLPAFCNVDIPNGGGGVCYWLARSGY [SEQ ID 13] Area: 102 to 124 - GGIYRELGAPDVGHPMSEVFRGC [SEQ ID 55] Peptide: ELGAPDVGHPMSE [SEQ ID 177]

[0340] Rice Protein 5: P14614 - 4 - MATIAFSRLSIYFCVLLLCHGSMAQLFGPNVNPWHNPRQGGFRECRFDRLQAFEPLRRVRSEAGVTEYFDEKNEQFQCTGTFVIRRVIEPQGLLVPRYSNTPGMVYIIQGRGSMGLTFPGCPATY QQQFQQFLPEGQSQSQKFRDEHQKIHQFRQGDIVALPAGVAHWFYNEGDAPVVALYVFDLNNNANQLEPRQKEFLLAGNNNREQQMYGRSIEQHSGQNIFSGFNNELLSEALGVNALVAKRLQGQ NDQRGEIIRVKNGLKLLRPAFAQQQEQAQQQEQAQAQYQVQYSEEQQPSTRCNGLDENFCTIKARLNIENPSHADTYNPRAGRITRLNSQKFPILNLVQLSATRVNLYQNAILSPFWNVNAHSLV YIVQGHARVQVVSNLGKTVFNGVLRPGQLLIIPQHYVVLKKAEHEGCQYISFKTNANSMVSHLAGKNSIFRAMPVDVIANAYRISREQARSLKNNRGEELGAFTPRYQQQTYPGFSNESENEALE [SEQ ID 14] Area: 372 to 397 - HSLVYIVQGHARVQVVSNLGKTVFNG [SEQ ID 56] Peptide: IVQGHARVQVVSNLGK [SEQ ID 178] Peptide: IVQGHARVQVVSNL [SEQ ID 179] Peptide: IVQGHARVQVVSN [SEQ ID 180] Area: 464 to 486 - ARSLKNNRGEELGAFTPRYQQQT [SEQ ID 57] Peptide: NNRGEELGAFTPR [SEQ ID 181] Peptide: GEELGAFTPR [SEQ ID 182] Area: 337 to 359 - LNSQKFPILNLVQLSATRVNLYQ [SEQ ID 58] Peptide: FPILNLVQLSATR [SEQ ID 183] Area: 210 to 293 - QMYGRSIEQHSGQNIFSGFNNELLSEALGVNALVAKRLQGQNDQRGEIIRVKNGLKLLRPAFAQQQEQAQQQEQAQAQYQVQYS [SEQ ID 59] Peptide: SIEQHSGQNIFSGFNNELLSEALGVNALVAK [SEQ ID 184] Peptide: LQGQNDQR [SEQ ID 185] Peptide: SGFNNELLSEALGVNALVAK [SEQ ID 186] Peptide: PAFAQQQEQAQQQEQAQAQY [SEQ ID 187] Peptide: VAKRLQGQNDQRGEI [SEQ ID 188] Peptide: ALVAKRLQGQNDQRGEI [SEQ ID 189] Peptide: LQGQNDQRGEIIR [SEQ ID 190] Area: 24 to 47 - AQLFGPNVNPWHNPRQGGFRECRF [SEQ ID 60] Peptide: PNVNPWHNPRQGGF [SEQ ID 191] Area: 164 to 186 - GVAHWFYNEGDAPVVALYVFDLN [SEQ ID 61] Peptide: FYNEGDAPVVALY [SEQ ID 192] Peptide: FYNEGDAPVV [SEQ ID 193] Peptide: FYNEGDAPVVAL [SEQ ID 194] Peptide: FYNEGDAPVVA [SEQ ID 195] Region : 424 to 463 - YISFKTNANSMVSHLAGKNSIFRAMPVDVIANAYRISREQ [SEQ ID 62] peptide : TNANSMVSHLAGK [SEQ ID 196] peptide : AMPVDVIANAYR [SEQ ID 197]

[0341] イネprotein 6 : Q0DEV5 - 5 - MSALTTSQLATSATGFGIADRSAPSSLLRHGFQGLKPRSPAGDGATSLSVTTSARATPKQQRSVQRGSRRFPSVVVYATGAGMNVVFVGAEMAPWSKTGLGDVLGGLPAMAANGHRVMVISPRYDQYKDAWDTSVVAEIKVADRYERVRF FHCYKRGVDRVFIDHPSFLEKVWGKTGEKIYGPDTGVDYKDNQMRFSLLCQAALEAPRILNLNNNPYFKGTYGEDVVFVCNDWHTGPLASYLKNNYQPNGIYRNAKVAFCIHNISYQGRFAFEDYPELNLSERFRSSFDFIDGYDTPVEGRK INWMCAGILEADRVLTVSPYYAEELISGIARGCELDNIMRLTGITGIVNGMDVSEWDPSKDKYITAKYDATTAIEAKANLKEALQAEAGLPVDRKIPLIAFIGRLEEQKGPDVMAAAIPELMQEDVQIVLLGTGKKKFEKLLKSMEEKYPGK VRAVVKFNAPLAHLIMAGADVLAVPSRFEPCGLIQLQGMRYGTPCACASTGGLVDTVIEGKTGFHMGRLSVDCKVVEPSDVKKVAATLKRAIKVVGTPAYEEMVRNCMNQDLSWKGPAKNWENVLLGLGVAGSAPGIEGDEIAPLAKENVAAP [SEQ ID NO:15] Region : 571 to 608 - KGPAKNWENVLLGLGVAGSAPGIEGDEIAPLAKENVAA [SEQ ID 63] Peptide : NWENVLLGLGVAGSAPGIEGDEIAPLAK [SEQ ID 198] Peptide: NVLLGLGVAGSAPGIEGDE [SEQ ID 199] Peptide: NWENVLLGLGVAGSAPGIEGDEIAPLAK [SEQ ID 200] Area: 458 to 488 - RAVVKFNAPLAHLIMAGADVLAVPSRFEPCG [SEQ ID 64] Peptide: FNAPLAHLIMAGADVLAVPSR [SEQ ID 201] Peptide: FNAPLAHLIM [SEQ ID 202] Peptide: FNAPLAHLIMAGADVLAVPSR [SEQ ID 203] Area: 545 to 566 - KRAIKVVGTPAYEEMVRNCMNQ [SEQ ID 65] Peptide: VVGTPAYEEMVR [SEQ ID 204] Area: 93 to 147 - APWSKTGGLGDVLGGLPPAMAANGHRVMVISPRYDQYKDAWDTSVVAEIKVADRY [SEQ ID 66] Peptide: TGGLGDVLGGLPPAMAANGHR [SEQ ID 205] Peptide: YDQYKDAWDTSVVAEIK [SEQ ID 206] Peptide: DAWDTSVVAEIK [SEQ ID 207] Peptide: VMVISPR [SEQ ID 208] Area: 305 to 413 - INWMKAGILEADRVLTVSPYYAEELISGIARGCELDNIMRLTGITGIVNGMDVSEWDPSKDKYITAKYDATTAIEAKALNKEALQAEAGLPVDRKIPLIAFIGRLEEQK [SEQ ID 67] Peptide: LTGITGIVNGMDVSEWDPSKDK [SEQ ID 209] Peptide: VLTVSPYYAEELISGIAR [SEQ ID 210] Peptide: EALQAEAGLPVDRK [SEQ ID 211] Peptide: YDATTAIEAK [SEQ ID 212] Peptide: IPLIAFIGR [SEQ ID 213] Peptide: AGILEADR [SEQ ID 214] Peptide: IPLIAFIGR [SEQ ID 215] Area: 158 to 202 - RGVDRVFIDHPSFLEKVWGKTGEKIYGPDTGVDYKDNQMRFSLLC [SEQ ID 68] Peptide: VFIDHPSFLEK [SEQ ID 216] Peptide: GPDTGVDYKDNQM [SEQ ID 217] Peptide: IYGPDTGVDYKDNQMR [SEQ ID 218] Peptide: IYGPDTGVDYK [SEQ ID 219] Region: 206 to 226 - LEAPRILNLNNNPYFKGTYGE [SEQ ID 69] Peptide: ILNLNNNPYFK [SEQ ID 220]

[0342] Protein P02855 Peptide: KNPQLQDLDI [SEQ ID 356] Protein P07730 Peptide: GQSTSQWQSSR [SEQ ID 357] Peptide: QSTSQWQSSR [SEQ ID 358] Protein P07728 Peptide: QSTSQWQSSR (also in P07730) [SEQ ID 359] Protein P13918 Peptide: EEEEQGEEEINK [SEQ ID 360] Protein P14323 Peptide: PSTNPWHSPR [SEQ ID 361] Peptide: AQAQDQYQQVQYSE [SEQ ID 362] Peptide: SEAGVTEYFDEKNELFQCTGTFVIRR [SEQ ID 363] Peptide: QAQAQDQYQQVQYSE [SEQ ID 363] Peptide: GSMGLTFPGCPAT (also in P14614) [SEQ ID 365] Peptide: GSMGLTFPGCPATY (also in P14614) [SEQ ID 366] Protein P14614 Peptide: LGAFTPRY [SEQ ID 367] Peptide: LGAFTPRYQQ [SEQ ID 368] Peptide: ALGVNALVAKRLQGQN [SEQ ID 369] Peptide: LGAFTPRYQ [SEQ ID 370] Peptide: GSMGLTFPGCPAT (also in P14323) [SEQ ID 371] Peptide: GSMGLTFPGCPATY (also in P14323) [SEQ ID 372] Protein P15838 Peptide: SNNPFKFLVPARQS [SEQ ID 373] Protein Q6K508 Peptide: CAGVFVIRR [SEQ ID 374] Protein Q6K7K6 Peptide: GSPLQSPRGF [SEQ ID 375] Peptide: RSSWQQQSY [SEQ ID 376] Peptide: SFGGSPLQSPR [SEQ ID 377] Peptide: YLPTKQLQPTW [SEQ ID 378] Peptide: GKPRSSWQQQ [SEQ ID 379] Peptide: FGGSPLQSPRG [SEQ ID 380] Protein Q9M3X6 Peptide: LNLLGFGINAENNE [SEQ ID 381]

[0343] Additional peptides [SEQ ID 381 - 417] LRGFSK

[0381] GALMLPHYN GALMLPHYNSR VFDGVLRPG LQSQND LQSQNDQRGEI QSQNDQRGEIIHVK RGEIIHVK RLQSQNDQ RLQSQNDQRG [SEQ ID 390] RLQSQNDQRGEIIH MPMP PMPL LEPDNR GIARLAGTSSVIN RSQNIF PNSM GHPM HPMS FLPQHTD [SEQ ID 400] EWQINEK GPQQYAEWQINEK PQQYAEWQ RGPQQYA HNPR WHN WDP HPSF PGQLQSFLLSGNQNQQNYLSGF QLQSFLLSGNQNQQNYLSGFSK [SEQ ID 410] QSFLLSGNQNQQ PGQLQSFLLSGN QSFLLSGNQ QNQQNYLSGFSK YLRGFS PVEMPTLLYPS RGPQQYAEWQINE [SEQ ID 417] TVFDGVLRPGQL LDALEPDNR RLQSQNDQRGEIIHVK [SEQ ID 420] VLDLAIPVNRPGQL HGPVEMPYTLLYPSSK [SEQ ID 422] GYYGEQQQQPGMTR [SEQ ID 423] Protein: P29835 - 5 - Rice SEEGYYGEQQQQPGMTR [SEQ ID 424] Protein: P29835 - 5 - Rice

[0344] Protein: P29835 - 5 - Rice MASKVVFFAAALMAAMVAISGAQLSESEMRFRDRQCQREVQDSPLDACRQVLDRQLTGRERFQPMFRRPGALGLRMQCCQQLQDVSRECRCAAIRRMVRSYEESMPMPLEQGWSSSSSEYYGGEGSSSEQGYYGEGSSEEGYYGEQQQQPGMTRVRLTRARQYAAQLPSMCRVEPQQCSIFAAGQY [SEQ ID 353] Protein: P02857 - 1 - Pea MAKLLALSLSFCFLLLGGCFALREQPQQNECQLERLDALEPDNRIESEGGLIETNPNNKQFRCAGVALSRATLQRNALRRPYYSNAPQEIFIQQGNGYFGMVFPGCPETFEEPQESEQGEGRRYRDRHQKVNRFREGDIIAVPTGIVFWMYNDQDTPVIAVSLTDIRSSNNQLDQMPRRFYLAGNHEQEFLQYQHQQGGKQEQENEGNNIFSGFKRDYLEDAFNVNRHIVDRLQGRNEDEEKGAIVKVKGGLSIISPPEKQARHQRGSRQEEDEDEEKQPRHQRGSRQEEEEDEDEEERQPRHQRRRGEEEEEDKKERGGSQKGKSRRQDNGLEETVCTAKLRLNIGPSSPDIYNPEAGRIKTVTSLDLPVLRWLKLSAEHGSLHKNAMFVPHYNLNANSIIYALKGRARLQVVNCNGNTVFDGELEAGRALTVPQNYAVAAKSLSDRFSYVAFKTNDRAGIARLAGTSSVINNNLPLDVVAATFNLQRNEARQLKSNNPFKFLVPARESENRASA [SEQ ID 354] protein : P09918 - 14 - Pisum sativum MFSGVTGILNRGHKIKGTVVLMRKNVLDINSLTTVGGVIGQGFDILGSTVDNLTAFLGRSVSLQLISATKPDATGKGKLGKATFLEGIISSLPTLGAGQSAFKIHFEWDDMGIPAGAFYIKNFMQTEFFLVSLTLDDIPNHGSIYFVCNSWIYNAKHHKIDRIFFANQTYLPSETPAPLVHYREEELNNLRGDGTGERKEWERIYDYDVYNDLGNPDSGENHARPVLGGSETYPYPRRGRTGRKPTRKDPNSESRSDYVYLPRDEAFGHLKSDFLTYGLKAVSQNVVPALESVFFDLNFTPNEFDSFDEVHGLYEGGIKLPTNILSQISPLPVLKEIFRTTDGENTLKYPPPKVIQVSRSGWMTDEEFAREMLAGVNPNVICCLQEFPPRSKLDSQIYGDHTSKISKEHLEPNLEGLTVEEAIQNKKLFL LDHHDSIMPYLRRINSTSTKAYATRTILFLNNNQNLKPLAIELSLPHPQGDEHGAVSYVYQPALEGVESSIWLAKAYVIVNDSCYHQLVSHWNLTHAVVEPFVIATNRHLSCLHPIYKLLYPHYRDTMNINSLARLSLVNDGGIIEKTFLWGRYSMEMSSKVYKNWVFTEQALPADLIKRGMAIEDSPSPCGVKLVVEDYPYAVDGLEIWAIIK TWVQDYVSLYYTSDEKLRQDSELQAWWKELVEVGHGDKKNEPWWPKMQTREDLIEVCSIVIWTASALHAAVNFGQYSYGGLILNRPTLSRRFMPEKGSAEFEELVKSPQKAYLKTITPKFQTLIDLSVIEILSRHASDELYLGERDNPNWTSDKRALEAFKKFGNKLAEIEKKLTQRNNDEKLRNHGPVEMPYTLLYPSSKEGLTFRGIPNSISI [SEQ ID 355] Bacterial protein 1 : P0C1U8 - 5 - MKGKFLKVSSLFVATLTTATLVSSPAANALSSKAMDNHPQQTQSSKQQTPKIQKGGNLKPLEQREHANVILPNNDRHQITDTTNGHYAPVTYIQVEAPTGTFIASGVVVGKDTLLTNKHVVDATHGDPHALKAFPSAINQDNYPNGGFTAEQITKYSGEGDLAIVKFSPNEQNKHIGEVVKPATMSNNAETQVNQNITVTGYPGDKPVATMWESKGKITYLKGEAMQYDLSTTGGNSGSPVFNEKNEVIGIHWGGVPNEFNGAVFINENVRNFLKQNIEDIHFANDDQPNNPDNPDNPNNPDNPNNPDEPNNPDNPNNPDNPDNGDNNNSDNPDAA [SEQ ID 16] Region: 92 to 117 - YIQVEAPTGTFIASGVVVGKDTLLTN [SEQ ID 70] Peptide: APTGTFIASGVVVGKD [SEQ ID 221]

[0345] Homolog of pea protein 1 (SEQ ID 1) >gi|137584|sp|P08438.1|VCL_VICFA RecName: Full=Vicilin; Flags: Precursor [Vicia faba] >gi|22057|emb|CAA68559.1| vicilin [Vicia faba var. minor] >gi|383931031|gb|AFH56916.1| vicilin [Vicia faba] MAATTLKDSFPLLTLLGIAFLASVCLSSRSRDQDNPPFVFESNRFQTLFENENGHIRLLQKFDQHSKLLENLQNYRLLEYKSKPHTIFLPQTDADFILVLSGKAILTVLLPNDRN SFSLERGDTIKLPAGTIGYLVNRDDEEDLRVLDLVIPVNRPGEPQSFLLSGNQNQPSILSGFSKNILEASFNTDYKEIEKVLLEEHGKEKYHRRGLKDRRQRGQEENVIVKISRKQ IEELNKNAKSSSKKSTSSEPFNLRREPIYSNKFGKFFEITPKRNPQDLNIFVNYVEINEGSLLLPHYNSRAIVTVNEGKGDFELVGQRNENQQGLREEYDEEKEQGEEE IRKQVQNYKAKLSPGDVLVIPAGYPVAIKASSNLNLVGFGINAENNQRYFLAGEEDNVISQIHKPVKELAFPGSAQEVDTLENQQSHFANAQPRERERGSQEIKDHLYSILGSF [SEQ ID 222] >gi|502105533|ref|XP_004492829.1| PREDICTED: vicilin-like isoform X1 [Cicer arietinum] ChickPea <h2 style=";text-align:left;direction:ltr">MAIKARFPLLVLLGIVFLASVCAKSDKENPFFFKSNNCQTLFENENGHVRLLQRFDKRSQLFENLQNYRLMEYNSKPHTLFLPQHNDADFILVVLRGRAILTVLNPNDRNT FKLERGDTIKLPAGTIAYLANRDDNEDLRVLDLAIPVNRPGQFQSFSLSGNENQQSYFQGFSKKILEASFNSDYEEIERVLLEEQEQKPEQRRGHKGRQQSQETDVIVKISR EQIEELSKNAKSNCKKSVSSESEPFNNLRSRSPIYSNRFGNFFEITPEKNPQLKDLDIFVNSVEIKEGSLLLPHFNSRATVILVVNEGKGEVELVGLRNENEQENKKEDEEE EEDRNVQVQRFQSKLSSGDVVVIPASHPFSINASSDLFLLGFGINAQNNQRNFLAGEEDNVISQIQRPVKEVAFPGSAEEVDRLLKNQRQSHFANAQPQQKRKGSQRIRSPF [SEQ ID 223]<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> >gi|29539109|emb|CAD87730.1| allergen Len c 1.0101 [Lens culinaris] Lentil<h2 style=";text-align:left;direction:ltr"> SRSDQENPFIFKSNRFQTIYENENGHIRLLQRFDKRSKIFENLQNYRLLEYKSKPHTIFLPQFTDADFILVVLSGKAILTVLNSNDRNSFNLERGDTIKLPAGTIAYLANRDDNEDLRVLDLAIPVNRPGQLQSFLLSGTQNQPSFLSGFSKNILEAAAFNTEYEIEKVLLEEQEQKSQHRRSLRDKRQEITNEDVIVKVSREQIEELS KNAKSSSKKSVSSESEPFNLRSRNPIYSNKFGKFFEITPEKNPQLQDLDIFVNSVEIKEGSLLLPNYNSRAIVIVTVNEGKGDFELVGQRNENQQEQREENDEEGQEEETTKQVQRYRARLSPDGVLVIPAGHPVAINASSDNLIGFGINAKNNQRNFLAGEEDNVISQIQRPVKELAFPGSSREVDRLLTNQKQSHFANAQPLQIE [SEQ ID NO:224]

[0346] Endogenous protein 2 (SEQ ID 2) >gi|29539111|emb|CAD87731.1| allergen Len c 1.0102 [Lens culinaris] SRSDQENPFIFKSNRFQTIENENGHIRLLQKFDKRSKIFENLQNYRLLEYKSKPHTLFLPQYTDADFILVVLSGKAVLTVLNSNDRNSFNLERGDTIKLPAG TIAYLANRDNEDLRVLDLAIPVNNPGQLESFLLSGTQNQPSFLSGFNKSILEAAFNTDYEEIEKVLLEDQEQHRRSLRDRRQEINKENVIVKVSREQIKE LSKNAKSSSKKSVSSESEPNLRSRNPIYSNKFGKFFEITPEKNPQLQDLDIFVNSVEIKEGSLLLPNYNSRAIVIVTVNEGKGYFELVGQRNENQREENDDEE EQEEETSTQVQRYRAKLSPGDVFVVPAGHPVAINASSDLNLIGFGINAKNNQRNFLAGEEDNVISQIQRPVKELAFPGSSREVDRLLTNQQSHFANAQPLQIE [SEQ ID 225] >gi|1297072|emb|CAA96514.1| vicilin precursor [Vicia narbonensis] MAAITMKVSFPLLMLLGISFLASVCVSSRSDQENPFIFKSNKFQTLFENDNGHIRLLQKFDERSKILENLQNYRLLEYKSKPRTIFLPQQTNADFILVVLSGKAILTVLKPDDRNSFNLERGDTIKLPAGTIAYLVNKDDNEDLRVLDLAIPVNGPDQLQSFLLSGSENQQSILSGFSKSVLEASFNTGYEEIEKVLLEEREKETQHRRSLRDKRQHSQDEDVIVKLSRGQIEELSRNAKSSSKKSVSSESEPFNLRSRNPIYSNKFGKFFEITPEKNPQLQDLDVLVNSVEIKEGSLLLPHYNSRAIVIVTVNDGKGDFEIVGQRNENRQGQRKEDDEEEEQGDENTNTQVQNYKAKLSRGDVFVIPAGHPVSIKASSNLDLLGFGINAKNNQRNFLAGEEDNVISQIDRPVKELAFPGSAQEVDRLLENQKQSHFANAQPQQRERGSHETRDHLSSILDAF [SEQ ID 226] >gi|28629838|gb|AAO45103.1| beta-conglycinin alpha' subunit [Glycine max] QYGHVRVLQRFNKRSQQLQNLRDYRILEFNSKPNTLLLPHHADADYLIVILNGTAILTLVNNDDRDSYNLQSGDALRVPAGTTYYVVNPDNDENLRMITLAIPVNKPGRFESFFLSSTQAQQSYLQGFSKNILEASYDTKFEEINKVLFGREEGQQQGEERLQESVIVEISKKQIRELSKHAKSSSRKTISSEDKPFNLRSRDPIYSNKLGKLFEITPEKNPQLRDLDVFLSVVDMNEGALFLPHFNSKAIVVLVINEGEANIELVGIKEQQQRQQQEEQPLEVRKYRAELSEQDIFVIPAGYPVVVNATSDLNFFAFGINAENNQRNFLAGSKDNVISQIPSQVQELAFPGSAKDIENLIKSQSESYFVDAQPQQKEEGNKGRKGPLSSILRAFY [SEQ ID 227]

[0347] Sequence 3 (SEQ ID 3) >gi|483449|emb|CAA83677.1| legume A [Vicia sativa] MAKLLALSLSFCFLLFSSCFALREQSQQNECQLERINALEPDNRIESEGGLIETWNPNNRQFRCARVALSRATLQRNALRRPYYSNAPQEIQGNGYFGMVFPGCPETHEEPQQSEQGEGRR YRDSHQKVNRFREGDIAVPTGIAFWMYNDQDTPVIAISLTDTGSSNNQLDQMPRRFYLAGNQEQEFLRYQHQGGKQDNDGNNIFSGFKRDFLEDAFNVNRHIVDRLQGRNEDEEKGAIVKV KGGLSIAPPERQERGSRQEEDEDEKEERQPSHHKSRRDEDDKKRHSQKGQSRRQGDNGLEETVCTAKLRANIGSSSPDIYNPQAGRIKTVTSLDLPVLRWLKLSAEHGSLHKNAMF VPHYNLNANSVIYALKGRARLQVVNCNGNTVFDGELEAGRALTVPQNYAVAAKSERFTYVAFKTDDRASIARLAGTSSVIDDLPLDVVAATFNMQRNEARQLKSNNPFKFLVPPRQSEMRASA [SEQ ID 228] >gi|657379551|gb|KEH23931.1| legumin A2 [Medicago truncatula] MAKLLALSLSLCFLLFSGCFAIREHQPHQKQQPQQNECQLEQLNALEPDNRIESEGGIIETWNPNNRQFRCAGVALSRCTLQRNSLRRPFYSNAPQEIFIQQGSGYFGMVFPGCPETFEEPQESEQRESRRIRESEQGESRRIRESEQGEGRRFRDSHQKVNRFREGDLIAVPTGTVFWMYNDQDTPVIAVSLIDTGSFQNQLDEMPRRFYLAGNQEQEFLQYQQQQVRGRGEQRRGREQQENEGGNIFSGFKRDFLEDALNVNRHIVDRLQGRNEDEEKGAIVKVRGGLSFVTPPERQSRHQGGSIIEEDEDEEDEWRRPHHQKSRRGEEEERPCRRGQKCERSNGLEETICTARLRQNIGSSSSPDIYNPEAGRIKTVTSFDLPALRWLRLSAEHGTLHRNAMFVPHYNLNANSAIYALRGRARLQVVNCNGNTVFDGELEAGRVLIVPQNFAVAAKSMSDRFQYVSFKTNDNAAIARLAGTQSTLSGVPMDVLAATYNMDRNEARQLKNNNLYKFLVPPRESERRAAA [SEQ ID 229] >gi|206712292|emb|CAR78996.1| legumin storage Protein 5 [Lotus japonicus] MAYKLFALSLSFCFLLFGGCFAIRQQSQQQNECQLERLNALKPDNRIESEAGYIETWNPTNNQFRCAGVALSRCTLRRNGLKRPSYSNAPQEIFIQQGSGIFGMIFPGCPETVEEPFESDQQGRRDRHQKVNRFREGDVIAVPPGVVFWMYNEEETPVIAVSLIDTGSYLNQLDQMPRRFYLSGNQEQEFLQYQRQEVRGREEENQGGNIFSGFGGEFLEDALNIDRNIVHKLQGRDE EQDKGAIVRVKGGLSVITPPERQSHRRGSEEEEDEEEDRPSRHQSRGGSRRNGLEETICTVRLRMNIGCSSPDIFNPQAGRIKTATGFDFPALRFLKLSAEHGSLNRNAMVVPHYNLNANSIIYALRGRAWIQVVNCKGNRIFDGELEEGQVLIVPQNFVVAARSMSDKFNYVAFKTNDMPTMAKLAGATSEIQAMPLEVIQNAFNLEREQAKQVKFNRFNFLFVPPRQSQRRASA [SEQ ID NO:230]

[0348] Endogenous protein 4 (SEQ ID 4) >gi|164512526|emb|CAP06312.1| cvc [Pisum abyssinicum] MATTVESRFPLLLFPGIIFLASVCVTYANYDEGSETRVPGQRERGRQEGEKEEKRHGEWRPSYEKEEDEEEKQKYRYQREKEDEEEKQKYRYQREKKEEKEVQPGRERWEREEDEEQVDEEWRGSQRRQDPEERARLRHREERTKRDRRHKREGEEEERSSESQEQRNPFLFKSNKFLTLFENENGHIRRLQRFDKRSDLFENLQNYRLVEYRAKPHTIFLPQHIDADLILVVLNGKAILTVLSPNDRNSYNLERGDTIKIPAGTTSYLVNQDDEEDLRVVDFVIPVNRPGKFEAFGLSENKNQYLRGFSKNILEASLNTKYETIEKVLLEEQEKKPQQLRDRKRRQQGGERDAIIKVSREQIEELRKLAKSSSKKSLPSEFEPFNLRSHKPEYSNKFGKLFEITPEKKYPQLQDLDILVSCVEINKGALMLPHYNSRAIVVLLVNEGKGNLELLGLKNEQQEREDRKERNNEVQRYEARLSPGDVVIIPAGHPVAISASSNLNLLGFGTNAENNQRNFLSGSDDN [SEQ ID 231] >gi|164512538|emb|CAP06318.1| cvc [Lathyrus annuus] MATTIKSRFPLLLLLGIIFLASVCVTWANYDEGSEPRVPGQRERGRQEGEKEEKRHGEWRPSYEEEYDEGLEPKVPGKRERGRQEGEKEEKRHEEWRPSEKEEDEEEKQKYNYQREKKEHKEVQPGRERWERKQQ DECQVEEDEEPGEEQWRGSKRHEDPERARLRHREEKTKSYVEDNEETSSKEGRNPFLFKSNKFLTLFENENGHIRRLQRFDERSDIFENLQNYRLVEYRAKPHTMFLPQHIDADLILVVLNGKAILTVLSPNDR NSYNLERGDTVKLPAGTTSYLVNQDDEEDLRVVDLAIPVNRPGKFEAFGLSANKNQYLRGFSKNILEASLNTKYETIEKVLLEERRDQKGRQQGQETNAIVKVSREQIEELRKLAKSSSKSSLLSEPLNLRSQ NPKYSNKFGKFFEITPQKKYPQLQDLDVSISCVEINKGALLLPHYNSRSIGILVNEGKGNLELVGFKNEQRQRENEETNKKLQRYEARLSSGDVVVIPEGHPVAISASSNLNLLGFGINAANNQRNFLTGSDDN [SEQ ID 232] >gi|164512558|emb|CAP06328.1| cvc [Villa villosa] MATTIKSRFPVLLLLGIIFLTSVCVTYANYDEGREPSVPGQRERGRQEGEKEEKRHGEWRPSEEDEEEKYKYEEGRVPGQRERGRQEGEKEEKRHGKWRPSEEEEDEEEKYRYEEGSEPRGPGQRETGRQEGEKEKQRPEREPSYEKE EDEEEKQKYQYHREKKEQREVRPGRERFHEDEEQWRGIQRHEDPEERARERYRAEIAKRQVEEEREERDIPHEREQRNPFLFKSNKFQTLFQNENGYIRRLQRFDKRSDLFENLQNYRLVEYRAKPHTIFLPQHIDADLIIVVLS GRAILTVLSPDDRNSYNLERGDTIKLPAGTSYLVNQDDEEDLRVVDLAIPVNRPGKVESFLLSGNKNQYLRGFSKNILEASFNTNYETIERVLLEEQDKESQSIGQRRSQRQETNALVKVSREQLEDLKRLAKSSSQELSSQF EPINLRSQNPKYSNKFGKVFEITPEKKYPQLQDLFVSSVDIKEGALMLPHYNSRAIVVLLVNEGRGNLELVGLKNEQQREKEDEQERNNQVQRYEARLSPGDVVIIPAGHPVAVRASSDLNLLAFGINAENNQRNFLAGSDNFLAGSDN [SEQ ID 233]

[0349] Sequence 5 (SEQ ID 5) >gi|357507721|ref|XP_003624149.1| Provicilin [Medicago truncatula] >gi|87162569|gb|ABD28364.1| Cupin, RmlC-type [Medicago truncatula] >gi|355499164|gb|AES80367.1| vicilin 47 kDa protein [Medicago truncatula] MAIKAPFQLLMLLGIFFLASVCVSSRDDRHDQENPFFFNANHFQTLFENENGHIRLLQRFDKRSKIFENLQNYRLLEYHSKPHTLFLPQHNDADFILAVLSGKAILTVLNPDNRN SFNLERGDTIKLPAGSIAYLANRDNEDLRVLDLAIPVNRPGKFQSFLSGSQNQFFFSGFSKNILEAAFNANYEEIERVLIEEEHEQEPQHRRGLRKDRRQQDSNVIVKVSRE QIEELSRHAKSSSRRSGSSESAPFNLRSREPIYSNEFGNFFEITPEKNPQLKDLDILVNYAEIREGSLLLPHFNSRATVIVVVDEGCGEFELVGQRNENQQREEDEQQEEERSQ QVQRYRARLSPGDVYVIPAGHPTVVSASSDLSLLGFGINAENNERNFLAGEEDNVISQIERPVKEVAFPPGSAQDVESLLKNQRQSYFANAQPQQREREEGRSQRQRELISSILGVF [SEQ ID 234] >gi|164512560|emb|CAP06329.1| convicilin [Vicia peregrina] MATTFKSRFSLLLLLGIIFLAFVCVTCANYDEGSEPRVPGQRERGRQEGEKEEQSRERHPQREPSREKEEDEEEKQKYDEGTEPRVPGQRERGRQEGEKEEQRRERHPGQREPSQEEDEEREESDRRQEGSSKSEEQRNPFLFKSNKFLTLFQNGNGHIRLLQRFDKRSDLFENLQNYRLLEYRAKPHTIFLPQHIDADLILVVLSGRAILTVLSPDDRNSYNLERGDTIKLPAGTTSYPLNQDDEEDLRVVDLAISVNRPGKVESFNLSGNKNQYLRGFSENILEASFNTKYETIEKVLLEEQDKESQQPRGQRLQRQETNALVKVSREQVEELKRLARTSSKKGVSSEFEPFNLRSHGPKYSNKFGKFFEITPEKKYPQLQDLDISVSSVEINEGALFLPHYNSRAIVVVLVDEGKGNLELVGFKNEQQEQREKEDEQEERNKQVQRYEAKLSPGDVVIIPAGHPVAVSASSNLNLLGFGINAENNQRNFLTGSDDN [SEQ ID 235] >gi|164512562|emb|CAP06330.1| convicilin [Vicia lutea] MATTIKLRFPLLLLLGVILLASVCVTCANYDEGSEPRVPGRPEGEKEEKHRGKLRPSYEKEEDEGEKQRYHYEKKEQKEAQPRREKKEQKEEEKQVEEESRESQRYEDPGERARERYRAEIIKRQVEKEREERDRRHQREGEEEEGSSKSRNPFLFKSNNFLTLFENENGHIRLLQRFDKRSDLFENLQNYRLVEYRAKPHTIFLPQHIDADLILVVLSGKAILTVLSPNNRNSYNLKRGDTIKLPAGTTSYLLNSDDEEDLRMVDLAISVNRPGKVESFNLSGNKNQYLRGFSKNILEASFNTKYETIEKVLLEEQDKESQQSIGQKRISQRQETNALVKVSREQIEEPKRLARSSSRKGVSSEFEPINLRSQRPKYSNKFGKFYEISPEKKYPQLQDLDVSVSSVEINEGALLLPHYNSRAIVTVLVNEGKGNLELIGFQNEQQGQREKEDEQQHERNKQVQRYDARLSSGDVVIIPAGHPVAVSASSNLDLLGFGINAENSQRNFLTGSDDN [SEQ ID 236]

[0350] Homolog of Rice Protein 1 (SEQ ID 6) >gi|573919041|ref|XP_006647142.1| PREDICTED: glutelin type-B 4-like [Oryza brachyantha] MATTTFSRFSIYFCVLLLCHGSMAQLFSPTLNPWHSSRRGGSRDCRFDRLQAFEPLRRVRSEAGVTEYFDERNEQFQCTGTFVIRRVIEPQGLLVPRYTNTPGVVYIMQGRGSMGLTFPGCPATYQQQFQQFLPEGQSQSQKFRDEHQKIHQFRQGDIVALPAGVAHWFYNEGDTPVVALYVFDINNSANQLEPRQKDFLLAGNNNREQQVYGRSIEKHSGQNIFSGFNHELLSEALGISTLAAKRLQGQNDHRGEIIRVRNGLQLLKPTFTQQQEQAQSQYQVQYSEKQQESTRCNGLDENFCTINARLNIENPSRADTYNPRAGRITHLNNQKFPILNLVQMSATRVNLYQNAILSPYWNVNAHSLVYMVQGHARVQVVSNLGKTVFNSVLRPGQLLIIPQHYVVLKKAEREGCQYIAFKTNANSIVSQLAGKNSILRAMPVDVVANAYRISREQARDLKNNRGEELGAFTPKFEQQSYPGLSNESESEASE [SEQ ID 237] >gi|2764800|emb|CAA54153.1| 12s globulin [Avena sativa] MATTSFPSVLFYSCIFLLYNGSMAQLFGQSFTPWQSSRQGGLKGCKFDRLQAFEPLRQVRSQAGVTEYFDEQNEQFRCTGVFVIRRVIEPQGLLLPQYHNAPGLVYILQGRGYTGLTFPGCPATFQQQFQPFDQAQDQSQSHLKDEHQRVHRFKQGDVIALPAGIVHWGYNDGDAPVVAIYVFDVNNNANQLEPRQKEFLLAGNNKEDQQFGQNIFSGFNIQLLSEALGISQQAAQRIQSQKEQRGEIIRVTQALQFLKPTMSQQELVEHQAYQPIQSQEGQSTQYQVGQSTQYQEGQSTQYQAGQSQDRSFNGLEENFCSLEARQNIGNPKRADTHNPRAGRITRLHGQNFPILNLVQMSATRVNLYQNAILSPFWNINAHSVVYMIQGHAQVQVVNNNGQTVFNDRLRQGQLLIVPQHYVVLKKAEREGCQYISFKTNPNSMVSHIAGKSSILRALPVDVLANAYRISRQEARNLKNNRGQESGVFTPKFTQTSFQPYPEGEDESSLTNKASE [SEQ ID 238] >gi|357130026|ref|XP_003566659.1| PREDICTED: 12S seed storage globulin 1-like [Brachypodium distachyon] >gi|357130028|ref|XP_003566660.1| PREDICTED: 12S seed storage globulin 1-like [Brachypodium distachyon] MAHTSFSSVLSYFCIFLLFHGSMAQVPGQGSTWQSPRQGGSRECSFDRLQTIEPLTQVRSQAGLTEYFDEQNEQFRCAGVSVIRRVIEPRGLLLPRYHNTPGLVYILEGSGFVGLAFPGCPETFLEQFQQSRQTQSTLGQSQCQSQSQKLGDVHQRVHQFTQGDVVALPAGVAHWFYNGGDAPVVAVYVFDVNNNANQLEPRQKEFLLAGNYNGVLQSGRNILNGLNAQLLSQAFGINEQTSRIIQNQNDGRGEIVRVEYGLQFLTPVVTQQQQKQPFLPIEPQEGQSSRNGLEENFCSLEPRQNIEDPNRADTYNPRAGSIARLNGQNFPILNLVQMSATRVNLQKNAIVSPFWNINAHSVVYVIQGQASVQVVNNQGRNVFNGLLRRGQLLIIPQNYVVLKKAESEGYQYIAFKTNANSMVSHIAGKNSILRALPVDVIANAYRISRQEAQNLKNNRGEEIGVLTPNFPQSSCQSYPIGDVDSSSTPKAQE [SEQ ID 239]

[0351] Homolog of Rice Protein 2 (SEQ ID 7) >gi|222622792|gb|EEE56924.1| hypothetical protein OsJ_06602 [Oryza sativa Japonica Group] MAQFSFGGSPLQSPRGFRGDQDSRHQCRFEHLTALEATHQQRSEAGFTEYYNIEARNEFRCAGVSVRRLVVESKGLVLPMYANAHKLVYIVQGRGVFGMALPGCPETFQSVRSPFEQEVATAGEAQSSIQKMRDEHQQLHQFHQGDVIAVPAGVAHWLYNNGDSPVVAFTVIDTSNNANQLDPKRREFFLAGKPRSSWQQQSYSYQTEQLSRNQNIFAGFSPDLLSEALSVSKQTVLRLQGLSDPRGAIIRVENGLQALQPSLQVEPVKEEQTQAYLPTKQLQPTWLRSGGACGQQNVLDEIMCAFKLRKNIDNPQSSDIFNPHGGRITRANSQNFPILNIIQMSATRIVLQNNALLTPHWTVNAHTVMYVTAGQGHIQVVDHRGRSVFDGELHQQQILLIPQNFAVVVKARREGFAWVSFKTNHNAVDSQIAGKASILRALPVDVVANAYRLSREDSRHVKFNRGDEMAVFAPRRGPQQYAEWQINEK [SEQ ID 240] >gi|218190679|gb|EEC73106.1| hypothetical protein OsI_07091 [Oryza sativa Indica Group] MAQFSFGGSPLQSPRGFRGDQDSRHQCRFEHLTALEATHQQRSEAGFTEYYNIEARNEFRCAGVSVRRLVVESKGLVLPMYANAHKLVYIVQGRGVFGMALPGCPETFQSVRSPFEQEVATAGEAQSSMQKMRDEHQQLHQFHQGDVIAVPAGVAHWLYNNGDSPVVAFTVIDTSNNANQLDPKRREFFLAGKPRSSWQQQSYSYQTEQLSRNQNIFAGFNPDLLSEALSVSKQTVLRLQGLSDPRGAIIRVENGLQALQPSLQVEPVKEEQTQAYLPTKQLQPTWSRSGGACGQQNGLDEIMCAFKLRKNIDNPQSSDIFNPHGGRITRANSQNFPILNIIQMSATRIVLQNNALLTPHWTVNAHTVMYVTAGQGRIQVVDHRGRSVFDGELHQQQILLIPQNFAVVVKARREGFAWVSFKTNHNAVDSQIAGKASILRALPVDVVANAYRLSREDSRRVKFNRGDEMAVFAPRRGPQQYAEWQINEK [SEQ ID 241] >gi|573922051|ref|XP_006648611.1| PREDICTED: glutelin type-A 1-like [Oryza brachyantha] MVDMSIVVPVCLTIFLLSQVCIAQVSFDGSPLYSSRGFRGGSASQQQCRFEHLAALEVTHQEKSEAGSIEYNTEARDEFRCARVSARRLVIESRGLVLPVYANAHKLLYIVQGRGVFGMALPGCPETFQSVRSAFEMATGDAESTRKLRDEHQKIHQFRQGDVIAVPPGVAHWLYNNGDSPVVAFSVIDFGNNANQLDPKPREFFLAGKPWGQVQYSYQSEQQSKHQNIFAGFNPDLLAEALSVSRQT AMRLQELNDQRGAIIRVEQGLQLALDPSFQAEQEQEEQPQEYLSSQQQQPTWSQRSGACVQNNGLDEIMCAFKVSKNINSAQSTDIFNPRGGRITRANSQNFPVLNIIQMSATRTVLQNNALLTPHWTVNAHTVMYVTAGQGRIQVVDHRGRTVFDGELRQQQILLIPQNFAVAVKARHEGFSWVSFKTSHNAIDSQIAGKGSILRALPVDVLAKAYMLSREESRTLKYNRADETLVFAPRPEIQLYAESEK [SEQ ID NO:242]

[0352] Endogenous protein 6 (SEQ ID 8) >gi|164512534|emb|CAP06316.1| cvc [Pisum fulvum] MATTTKSRFPLLLLLGIIFLASVVCVTYANYDEGSEPRVPGRRERGRQEGEKEEKRHGEWRPSYEKEEDEEEGQRERGRQEGEKEEKRHGEWGPSYEKQEDEEEKQKYRYQREKEDEEEKQKYRYQREKKEQKEVQPGRERWEREEDEEHVDEEWRGSQRHEDPEERARLRYREERTKRDRRHQREGEEEERSSESQERRNPFLFKSNKFQTLFENENGHIRLLQRFDKRSDLFENLQNYRLVEYRAKPHTIFLPQHIDADLILVVLSGKAILTVLSPNARNSYNLERGDTIKLPAGTTSYLVNQDDEEDLRLVDLVIPVNGPGKFEAFDLSKNKNQYLRGFSKNILEASYNTKYETIEKVLLEEQEKTDAIVKVSREQIEELRKHAKSSSKKIFPSEFEPINLRNHKPEYSNKFGKLFEITPEKKYPQLQDLDIFVSCVEINEGALMLPHYNSRAIVVLLVNEGKGNLELLGLENEQQEREDRKERNNEVQRYEARLSPGDVVIIPAGHPVAITASSNLNLLAFGINAENNQRNFLSGSDDN [SEQ ID 243] >gi|164512526|emb|CAP06312.1| cvc [Pisum abyssinicum] MATTHEWSRFPLLLFPGIIFLASVCVTYANYDEGSETRVPGQRERGRQEGEKEEKRHGEWRPSYEKEEDEEEKKYRYQREKEDEEEKQKYRYQREKKEEKEVQPGRERWEREEDEEQVDEEWRGSQRRQDP EERARLRHREERTKRDRRHKREGEEEERSSESQRNPFLFKSNKFLTLFENENGHIRRLQRFDKRSDLFENLQNYRLVEYRAKPHTIFLPQHIDADLILVVLNGKAILTVLSPNDRNSYNLERGDTIKIPA GTTSYLVNQDDEEDLRVVDFVIPVNRPGKFEAFGLSENKNQYLRGFSKNILEASLNTKYETIEKVLLEEQEKPQQLRDRKRRQQGGERDAIIKVSREQIEELRKLAKSSSKKSLPSEFEFEFNLRSHKPEY SNKFGKLFEITPEKKYPQLQDLDILVSCVEINKGALMLPHYNSRAIVVLLVNEGKGNLELLGLKNEQQEREDKERNNEVQRYEARLSPGDVVIIPAGHPVAISASSNLNLLGFGTNAENNQRNFLSGSDDN [SEQ ID 244] >gi|164512558|emb|CAP06328.1| cvc [Villa villosa] MATTIKSRFPVLLLLGIIFLTSVCVTYANYDEGREPSVPGQRERGQEGEKRHGEWRPSEEDEEEKYEEGRVPGQRERRQEGEKREKRHGKWRPSEEEDEEKYRYEEGSEPRGPGQRETGRQEGEKEKQRPEREPSYEKE EDEEEKQKYQYHREKKEQREVRPRGRERFERHEDEEQWRGIQRHEDPEERARERYRAEIAKRQVEEEREERDIPHEREQRNPFLFKSNKFQTLFQNENGYIRRLQRFDKRSDLFENLQNYRLVEYRAKPHTIFLPQHIDADLIIVVLS GRAILTVLSPDDRNSYNLERGDTIKLPAGTTSYLVNQDDEEDLRVVDLAIPVNRPGKVESFLLSGNKNQYLRGFSKNILEASFNTNYETIERVLLEEQDKESQQSIGQKRRSQRQETNALVKVSREQLEDLKRLAKSSSQEGLSSQF EPINLRSQNPKYSNKFGKVFEITPEKKYPQLQDLDLFVSSVDIKEGALMLPHYNSRAIVVLLVNEGRGNLELVGLKNEQQEQREKEDEQQERNNQVQRYEARLSPGDVVIIPAGHPAVRASSDLNLAFGINAENNQRNFLAGSDDN [SEQ ID NO:245]

[0353] Endogenous protein homologue 7 (SEQ ID 9) >gi|164512536|emb|CAP06317.1| cvc [Lathyrus hirsutus] MAIIIKSRFPLLLLLGIIFLASVCATWANYDEGSEPRVPGQRERGQEGEKAEKSHEKWRPSYEEEEYDEGSEPRVPGKRERGRQEGEKEEKRHGEWRPSHEEEYDEGSEPRVPTHGERGRQEGEKEEKRHEEWRPSYEKEEDEE EKEKYKYQREKKEQKEVQPGREKWERQDEKHVEEDEDQEEEQWRGSKRREDPEERARLRYREERTKSNVEEETEERRNPFLFKSNKFLTLFENENGHIRRLQRFDERSDIFENLQNYRLVEYKAKPHTMFLPQHIDADLIIVV LNGKAILTVLSPNDRNSYNLERGDTIKLPAGTTSYLVNQDDEEDLRVVDLAIPVNRPGKFEAFGLSANKNQYLRGFSKNILEAFLNTKYETIEKVLLEEQERRDRKGRQQGQETNAIVKVSREQIEELRKLAKSSSSKKSLLSESEPINLRSQNPKYSNKFGKLFEITPEKKYPQLQDLDVSISCVEINEGAPLLPHYNSRAIVLLLVNEGKGNLELVGFKNEQQRRENEERNKKVQRYEARLSPGDVVVIPAGHPVAISASLNLNLVGFGVNAENNQRNFLTGSDDN [SEQ ID 246] >gi|164512542|emb|CAP06320.1| cvc [Lathyrus cicera] MATIIKSRFPLLLLLGIIFLASVCVTLANYDEGSEPRVPAQRERGRQEGEKEEKRHGEWRPSHEKEYDEGSEPRVPGRRERGRQEGEKEEKRHGEWRPSYEKEYDEGSEPRVPGRRERGRQEGEKEEKRHGEWRPSYEKEYDEEEKQKYQYEREKEEQKEVQPGRERWERKEDEEKEEDQWRGSQRHEDPEERARLRYRKERTKKYVEEDTEETSSESQGRRNPFLFKSNKFLTLFENENGYIRRLQRFDERSDIFENLQNYRLVEYRAKPHTIFLPQHIDADLILVILNGKAILTVLSPNDRNSYNLERGDTIKLPAGTTSYLVNEDDEEDLRVVDLVIPVNRPGKFEAFDLNQYLGGFSKSVLEASLNTKYETIEKVLLEEQQKQGQETNAIVKVSREQIEELRKLAKSSSKKSLLSELEPVNLRSHSPKYSNKFGKFFEITPEKKYPQLQDLDVSISCVEINEGALLLPHYNSRAIVVVLVNEGKGNLELLGVQNEDEQQERKERNKEVQRYEARLSPGDVVIIPSGHPVAVSASSNLNLLGFGINAENNQRNFLSGSDDN [SEQ ID 247] >gi|164512544|emb|CAP06321.1| convicilin [Lathyrus sativus] MATIIKSRFPLLLLLGIIFLASVCVTYANYDEGSEPRVPAQRERGRQEGEKEEKRHGEWRPSSEKEYDEGSEPRVPGRRERGRQEGEKEEKRHGEWRPSYEKEYDEEEKQKYQYEREKKEQKEVEPGRERWERKEDEEKEEDQWRGSQRHEDPEERARLRYRKERTKKYVEEDTEETSSESQGRRNPFLFKSNKFLTLFENENGYIRRLQRFDERSDLFENLQNYRLVEYRAKPHTIFLPQHIDADLILVILNGKAILTVLSPNDRNSYNLERGDTIKLPAGTTSYLVNEDDEEDLRVVDLVIPVNRPGKFEAFDLNQYLGGFSKSVLKASLNTKYETIEKVLLEEQQKQGQETNAIVKVSREQIEELRKLAKSSSKKSLLSELEPVNLRSHSPKYSNKFGKFFEITPEKKYPQLQDLDVSISCVEINEGALLLPHYNSRAIVVLLVNEGKGNLELLGVQDEDEQQERKKRNKEVQRYEARLSPSDVVIIPAGHPVAVSASSNLNLLGFGINAENNERNFLSGSDDN [SEQ ID 248]

[0354] Homolog of rice protein 3 (SEQ ID 10) >gi|573918992|ref|XP_006647120.1| PREDICTED: glutelin type-B 2-like [Oryza brachyantha] MATTVFSRFSTYFCVLLLCHGSMAQLFNPSTNPWHNPRQGSSRECRFDRLQPFEPLRKVRSEAGVTEYFDEKNELFQCTGTFVIRRVIQPQGLLVPRYTNAPGLVYIIQGRGSIGLTFPGCPATYQQQFQQFLPQEQSQSQKFRDEHQKIHQFRQGDIVALPAGVAHWFYNDGDAPVVAVYVYDVKNSANQLEPRQREFLLGGNNMRAQQVYGSSAEQHSRQNIFSGFGVEILSEALGISTVTTKRLQSQNDQRGEIIHVKNGLQFLKPTLTQQQEQAQAQYQEVQYSEQQQTSSRWNGLDENFCTIKARMNIENTSRADTYNPRAGRTTSLNSQKFPILNLVQMSATRVNLYQNAILSTFWNVNAHSLVYTIQGRARVQVVSNFGKTVFDGELRPGQLLIIPQHYVVLKKAQREGFRYIAIKTNANAFVSQLVGKNSVFRSLPVDVIANVYRISREQARSLKNNRGEEHGAFAPRSQQQSYPGFSNQSESETSE [SEQ ID 249] >gi|573919041|ref|XP_006647142.1| PREDICTED: glutelin type-B 4-like [Oryza brachyantha] MATTTFSRFSIYFCVLLLCHGSMAQLFSPTLNPWHSSRRGGSRDCRFDRLQAFEPLRRVRSEAGVTEYFDERNEQFQCTGTFVIRRVIEPQGLLVPRYTNTPGVVYIMQGRGSMGLTFPGCPATYQQQFQQFLPEGQSQSQKFRDEHQKIHQFRQGDIVALPAGVAHWFYNEGDTPVVALYVFDINNSANQLEPRQKDFLLAGNNNREQQVYGRSIEKHSGQNIFSGFNHELLSEALGISTLAAKRLQGQNDHRGEIIRVRNGLQLLKPTFTQQQEQAQSQYQVQYSEKQQESTRCNGLDENFCTINARLNIENPSRADTYNPRAGRITHLNNQKFPILNLVQMSATRVNLYQNAILSPYWNVNAHSLVYMVQGHARVQVVSNLGKTVFNSVLRPGQLLIIPQHYVVLKKAEREGCQYIAFKTNANSIVSQLAGKNSILRAMPVDVVANAYRISREQARDLKNNRGEELGAFTPKFEQQSYPGLSNESESEASE [SEQ ID 250] >gi|109894635|gb|ABG47337.1| glutelin precursor [Zizania latifolia] MNMATINGPTIFFTVCLFLLCHGSLAQLLGQSTSQWQSSHRGSSRQCRFDRLQAFEPVRSVRSQAGTTEFFDASNELFQCAGVSIVRRIIEPRGLLLPQYTNGATIMYIIQGRGITGQTFFPGCPE SYQQQFQQSMQQLTGSQSQSQKFKDEHQKINRFRQGDVIALPAGVAHWCYNDGEVPVVAIYVIDINNAANQLDPRQRDFLAGNMRSPQAYRREVENQSQNIFSGFSAELLSEALGISTGVARQ LQCQNDQRGEIVRVEHGLSLLQPYASLQEQEQQQPRERYQVTQHQQSQYGGGCSNGLDETFCAMRIWQNIDNPNLADTYNPRAGRVTNLNSQKFPILNLIQMSAVKVNLYQNALLSPFWNINS HSVVYVTQGCARVQVVNNNGKTVFNGELRRGQLLIIPQHYVVVKKAQREGCAYIAFKTNPNSMVSHIVGKSSIFRALPTDVLANAYRISREDAQRLKHNRGDELGAFTPLQYKSYQDVSSVAASS [SEQ ID 251]

[0355] Package 4 (SEQ ID 11) >gi|531874314|gb|AGT59174.1| glutelin, partial [Oryza sativa Indica Group] CRFDRLQAFEPIRSVRSQAGTTEFFDVSNEQFQCTGVSAVRVIEPRGLLLPHYTNGASLVYIIQGRGITGPTFPGCPESYQQFQQSGQQLTESQSQSHKFKDEHQKIHRF RQGDVIALPAGVAHWCYNDGEVPVVAIYVTDLNNGANQLDPRQRDFLAGNKRNPQAYRREVEERSQNIFSGFSTELLSEALGVSSQVARQLQCQNDQRGEIVRVEHGLSLLQP YASLQEQGQVQSRERYQEGQYQQSQYGSGCSNGLDETFCTMKVRQNIDNPNRADTYNPRAGRVTNLNTQNFPILNLVQMSAVKVNLYQNALLSPWNINAHSVVYITQGRA RVQVVNNNGKTVFNGELRRGQLLIIPQHYAVVKKAQREGCAYIAFKTNPNSMVSHIAGKSSIFRALPNDVLANAYRISREEAQRLKHNRGDEFGAFTPIQYKSYQDVYNAAESS [SEQ ID 252] >gi|109894635|gb|ABG47337.1| glutelin precursor [Zizania latifolia] MNMATINGPTIFFTVCLFLLCHGSLAQLLGQSTSQWQSSHRGSSRQCRFDRLQAFEPVRSVRSQAGTTEFFDASNELFQCAGVSIVRRIIEPRGLLLPQYTNGATIMYIIQGRGITGQTFPGCPESYQQQFQQSMQAQLTGSQSQSQKFKDEHQKINRFRQGDVIALPAGVAHWCYNDGEVPVVAIYVIDINNAANQLDPRQRDFLLAGNMRSPQAYRREVENQSQNIFSGFSAELLSEALGISTGVARQLQCQNDQRGEIVRVEHGLSLLQPYASLQEQEQKQEQPRERYQVTQHQQSQYGGGCSNGLDETFCAMRIWQNIDNPNLADTYNPRAGRVTNLNSQKFPILNLIQMSAVKVNLYQNALLSPFWNINSHSVVYVTQGCARVQVVNNNGKTVFNGELRRGQLLIIPQHYVVVKKAQREGCAYIAFKTNPNSMVSHIVGKSSIFRALPTDVLANAYRISREDAQRLKHNRGDELGAFTPLQYKSYQDVSSVAASS [SEQ ID 253] >gi|472867|emb|CAA52764.1| 11S globulin [Avena sativa] MATTSFPSMLFYFCIFLLFHGSMAQLFGQSSTPWQSSRQGGLRGCRFDRLQAFEPLRQVRSQAGITEYFDEQNEQFRCTGVSVIRRVIEPQGLVLPQYHNAPALVYILQGRGFTGLTFPGCPATFQQQFQPFDQSQFAQGQRQSQTIKDEHQRVQRFKQGDVVALPAGIVHWCYNDGDAPIVAIYVFDVNNNANQLEPRQKEFLLAGNNKREQQSGNNIFSGLSVQLLSEALGISQQAAQRIQSQNDQRGEIIRVSQGLQFLKPIVSQQVPGEQQVYQPIQTQEGQATQYQVGQSTQYQVGKSTPYQGGQSSQYQAGQSWDQSFNGLEENFCSLEARKNIENPQHADTYNPRAGRITRLNSKNFPILNIVQMSATRVNLYQNAILSPFWNINAHSVIYMIQGHARVQVVNNNGQTVFNDILRRGQLLIVPQHFVVLKKAEREGCQYISFKTNPNSMVSHIAGKSSILRALPIDVLANAYRISRQEARNLKNNRGEEFGAFTPKLTQKGFQSYQDIEEGSSSPVRASE [SEQ ID 254]

[0356] Homolog of rice protein 5 (SEQ ID 12) >gi|225959|prf||1404367A glutelin MASTNRPIVFFTVCLFLLCDGSLAQQLLGQSTSQWQSSRRGSPRGCRFDRLQAFEPIRSVRSQAGTTEFFDVSNELFQCTGVSVVRRVIEPRGLLLPHYTNGASLVYIIQGRGITGPTFPGCPETYQQQFQQSGQAGLTESQSQSHKFKDEHQKIHRFRQGDVIALPAGVAHWCYNDCEVPVVAIYVTDINNGANQLDPRQRDFLLAGNKRNPQAYRREVEEWSQNIFSGFSTELLSEAFGISNQVARQLQCQNDQKGEIVRVERGLSLLQPYASLQEQEQGQMQSREHYQEGGYQQSQYGSGCPNGLDETFCVNKVRQNIDNPNRADTYNPRAGRVTNLSQNFPILNLVQMSAVKVNLYQNTDTWISMGQEENALLSPFWNINAHSIVYITQGRAQVQVLRRGQLLIVPQHYVVVKKAQREGCAYIAFKTNPNSMVSHIAGKSSIFRALPTDVLANAYRISREEAQRLKHNRGDEFGAFTPLQYKSYQDVYNVAESS [SEQ ID 255] >gi|573943558|ref|XP_006654150.1| PREDICTED: glutelin type-A 3-like [Oryza brachyantha] MKSSIVFSTICLVLLCHGSLAQLLSQSTSQWQSSRRGSPRQCRFDQLQAFEPIRTVRSQAGVTEFYDVSNELFQCTGVSVVRRVIEPRGLLLPHYSNGATLVYIIQGRGITGPTFPGCPETYQQQFQQSGEAQPFEGQSHKFRDEHQKIHRFRQGDVVALPAGVAHWCYNDGEVPIVAIYVTDIYNSANQLDPRHRDFFLAGNNKVAQQLYRSEARENSKNIFGGFSVELLSEALGISRGVARQLQCQNDQRGEIVRVEHGLALLQPYASVQEQQQEQVQSRDYEQTQYQQKQPQGSCSNGLDETFCTMRLRQNIDNPNLADTYNPKAGRITYLNGQKFPILNLVQMSAVKVNLYQNAVLSPFWNINAHSVVYITQGRARVQVVNNNGKTVFDGELRQGQLLIIPQHHVVLKKAQREGCSYIALKTNPNSIVSHIAGKNSIFRALPGDVVTNAYRISREEAKRIKHNRGDESGVFAPSHAYRSYQDMSVAA [SEQ ID 256] >gi|721641733|ref|XP_010231907.1| PREDICTED: 12S seed storage globulin 1-like [Brachypodium distachyon] MAHTFSSSFLSYFCLFLLFHGSMAQVLGQVSTWQSSRQGGSRDCSFDRLQAIEPVTQVRSQAGLTEYFDEQNEQFRCAGVFVIRRVIEPRGLLLLPRYHNTPGLVYILQGNGFVGLTFPGCPET FREQFQQFRQTQSTLGQSQCQSQKLGDVHQRVHQFTQGDVVALPTGVAHWIYNGGDAPVVIVYVFDVNNNQLEPRQKEFLLGGNYNGVLQYGQNIFSGFNAQLLSQAFGINEQTSQRIQNQ NDGRGDIIRVDNGLQFLKPVVTQQQPEQPFMPIQHQTGQSSRNGLEENFCSLEPRQNIEDPNRADTYNPRAGSITRLNGQNFPILNLVQMSATRVNLQKNAILSPFWNINAHSVVYVIQGHAL VQVVNNQGHNVFNGLLHRGQLLIPQNYVVLKKAESEGYQYIAFKTNANSMVSHIAGKNSILRALPVDVIANAYRISRQEAQNLKNNRGEETGVLTPNFSQSTCQSYQTEDVQSLRPMSHWSE [SEQ ID 257]

[0357] Package 6 (SEQ ID 13) >gi|169244463|gb|ACA50505.1| seed allergenic protein RAG2 [Oryza sativa Japonica Group] MASNKVVFSALLIVSVLAATATMADHHKDQVVYSLGERCQPGMGYPMYSLPRCRAVVKRQCVGHGAPGGAVDEQLRQDCCRQLAAVDDSWCRCSALNHMVGGIYRELGATDVGHPMAXVFPGCRRGDLERAAASLPAFCNVDIPNGTGGGGGLERAASLPAFCNVDIPNGTGGGGLPRCRQLAAVDDSWCRCSALNHMVGGIYRELGATDVGHPMAXVFPGCRRGDLERAAASLPAFCNVDIPNGTGGGGPRGLERAAASLPAFCNVDIPNGTGGGGLPRCRQLAAVDDSWCRCSALNHMVGGIYRELGATDVGHPMAXVFPGCRRGDLERAAASLPAFCNVDIPNGTGGGGGLYPRYGYQ28 IDWRTYGYRQLGATDVGHPMAXW >gi|5777592|emb|CAA44001.1| low molecular weight globulin [Oryza sativa] MASNKVVFSALLLIIVSVLRRDGTMADHHKDQVVYSLGERCQPGMGYPMYSLPRCRAVVKRQCVGHGAPGAVDEQLRQDCCRQLAAVDDSWCRCSALNHMVGGIYRELGATDVGHPMAEVFPGCRRGDLERAAASLPAFCNVDIPNGTGGVCYPRGGWGGQGYRQ2959] >gi|115471175|ref|NP_001059186.1| Os07g0214600 [Oryza sativa Japonica Group] >gi|23616954|dbj|BAC20657.1| allergen RA16 [Oryza sativa Japonica Group] >gi|113610722|dbj|BAF21100.1| Os07g0214600 [Oryza sativa Japonica Group] >gi|125557687|gb|EAZ03223.1| hypothetical protein OsI_25372 [Oryza sativa Indica Group] MASNKVVISALLVVVVSVLAATTTMADHHQEQVVYTPGQLCQPGIGYPTYPLPRCRAFVKRQCVAPGTVDEQVRRGCCRQLAAIDSSWCRCDALNHMLRIIYRESGAADAGHPMAEVFRGCRRGDIERAAASLPAFCNVDIPNGVGGGYWLPGTGGY

[260] IDGY

[0358] Package 7 (SEQ ID 14) >gi|115445309|ref|NP_001046434.1| Os02g0248800 [Oryza sativa Japonica Group] >gi|37993738|gb|AAR06952.1| glutelin type-B [Oryza sativa Japonica Group] >gi|47497729|dbj|BAD19794.1| glutelin type-B [Oryza sativa Japonica Group] >gi|113535965|dbj|BAF08348.1| Os02g0248800 [Oryza sativa Japonica Group] >gi|215768942|dbj|BAH01171.1| unnamed protein product [Oryza sativa Japonica Group] >gi|284431772|gb|ADB84627.1| glutelin [Oryza sativa Japonica Group] MTISVFSRFSIYFCVLLLCNGSMAQLFDPATNQWQTHRQGSFRECRFERLQAFEPLQNVRSEAGVTEYFDETNELFQCTGTFVIRRVIQPQGLLIPRYANTPGMVYIIQGRGSMGLTFPGCPATYQQQSQQFLFQGESQSQKFIDEHQKIHQFRQGDIVVLPTGVAHWFYNDGDTPVVALYVYDINNSANQLEPRHREFLLAGKNNRVQQVYGRSIQQHSGQNIFNGFSVEPLSEALNINTVTTKRLQSQNDQRGEIIHVKNGLQLLKPTLTQRQEQEQAQYQEVQYSEKPQTSSRWNGLEENLCTIKTRLNIENPSRADSYDPRAGRITSLDSQKFPILNIIQMSATRVNLYQNAILTPFWNVNAHSLMYVIRGRARVQVVSNFGKTVFDGVLRPEQLLIIPQNYVVLKKAQHEGCQYIAINTNANAFVSHLAGVDSVFHALPVDVIANAYCISREEARRLKNNRGDEYGPFPPRLQQQIYPEFSNESKGETSE [SEQ ID 261] >gi|428674402|gb|AFZ41188.1| glutelin, partial [Oryza sativa Japonica Group] LLCHGSMAQIFSLGINPWQNPRQGGSRECRFDRLQAFEPLRKVRHEAGVTEYFDEKNEQFQCTGTLVIRRIIEPQGLLLPRYSNTPGLVYIIQGTGVLGLTFPGCPATYQKQFRHFGLEGGSQRQGKKLRDENQKIHQFRQGDVVALPSGIPHWFYNEGDTPVVALFVFDVNNNANQLEPRQKEFLLAGNNIEQQVSNPSINKHSGQNIFNGFNTKLLSEALGVNIEVTRRLQSQNDRRGDIIRVKNGLRLIKPTITQQQEQTQDQYQQIQYHREQRSTSKYNGLDENFCAIRARLNIENPNHADTYNPRAGRITNLNSQKFSILNLVQMSATRVNLYQNAILSPFWNINAHSLVYTIQGRARVQVVSNHGKAVFNGVLRPGQLLIIPQNYVVMKKAELEGFQFIAFKTNPNAMVNHIAGKNSVLRAMPVDVIANAYRISRQEARSLKNNRGEEIGAFTPRYQQQKIHQEYSNPNESETQ [SEQ ID 262] >gi|226510|prf||1515394A seed storage globulin MATTRFPSLLFYSCIFLLCNGSMAQLFGQSFTPWQSSRQGGLRGCRFDRLQAFEPLRQVRSQAGITEYFDEQNEQFRCAGVSVIRRVIEPQGLLLPQYHNAPGLVYILQGRGFTGLTFPGCPATFQQQFQPFDQARFAQGQSKSQNLKDEHQRVHHIKQGDVVALPAGIVHWCYNDGDAPIVAVYVFDVNNNANQLEPRQKEFLLAGNNKREQQFGQNIFSGFSVQLLSEALGISQQAAQKIQSQNDQRGEIIRVSQGLQFLKPFVSQQGPVEHQAYQPIQSQQEQSTQYQVGQSPQYQEGQSTQYQSGQSWDQSFNGLEENFCSLEARQNIENPKRADTYNPRAGRITHLNSKNFPTLNLVQMSATRVNLYQNAILSPYWNINAHSVMHMIQGRARVQVVNNHGQTVFNDILRRGQLLIIPQHYVVLKKAEREGCQYISFKTTPNSMVSYIAGKTSILRALPVDVLANAYRISRQESQNLKNNRGEEFGAFTPKFAQTGSQSYQDEGESSSTEKASE [SEQ ID 263]

[0359] Homolog of Rice Protein 8 (SEQ ID 15) >gi|83375868|gb|ABC17777.1| waxy [Oryza rufipogon] MSALTTSQLATSATGFGIADRSAPSSLLRHGFQGLKPRSPAGGDATSLSVTTSARATPKQQRSVQRGSRRFPSVVVYATGAGMNVVFVGAEMAPWSKTGGLGDVLGGLPPAMAANGHRVMVISPRYDQYKDAWDTSVVAEIKVADRYERVRFFHCYKRGVDRVFVDHPSFLEKVWGKTGEKIYGPDTGVDYKDNQMRFSLLCQAPRILNLNNNPYFKGTYGEDVVFVCNDWHTGPLASYLKNNYQPNGIYRNAKVAFCIHNISYQGRFAFEDYPELNLSERFRSSFDFIDGYDTPVEGRKINWMKAGILEADRVLTVSPYYAEELISGIARGCELDNIMRLTGITGIVNGMDVSEWDPSKDKYITAKYDATTAIEAKALNKEALQAEAGLPVDRKIPLIAFIGRLEEQKGPDVMAAAIPELMQEDVQIVLLGTGKKKFEKLLKSMEEKYPGKVRAVVKFNAPLAHLIMAGADVLAVPSRFEPCGLIQLQGMRYGTPCACASTGGLVDTVIEGKTGFHMGRLSVDCKVVEPSDVKKVAATLKRAIKVVGTPAYEEMVRNCMNQDLSWKGPAKNWENVLLGLGVAGSAPGIEGDEIAPLAKENVAAP [SEQ ID 264] >gi|297614332|gb|ADI48504.1| glycogen synthetase [Oryza officinalis] MSALTTSQLATSATGFGIADRSAPSSLLRHGFQGLKPRSPAGGDASSLSVTTSARATPKQQRSVQRGSRRFPSVVVYATGAGMNVVFVGAEMAPWSKTGGLGDVLGGLPPAMAANGHRVMVISPRHDQYKDAWDTSVVAEIKVADRYERVRFFHCYKRGVDRVFIDHPSFLEKVWGKTGEKIYGPDTGVDYKDNQMRFSLLCQAALEAPRILNLNNNPYFKGTYGEDVVFVCNDWHTGPLPSYLKNNYQPNGIYRNAKVAFCIHNISYQGRFAFEDYPELNLSERFRSSFDFIDGYDTPVEGRKINWMKAGILESDRVLTVSPYYAEELISGIARGCELDNIMRLTGITGIVNGMDVSEWDPSKDKYIAAKYDATTAIEAKALNKEALQAEAGLPVDRKIPLIAFIGRLEEQKGPDVMAAAIPELMQENVQIVLLGTGKKKFEKLLKSMEEKYPGKVRAVVKFNAPLAHLIMAGADVLAVPSRFEPCGLIQLQGMRYGTPCACASTGGLVDTVIEGKTGFHMGRLSVDCKVVEPSDVQKVATTLKRAIKIVGTPAYNEMVRNCMNQDLSWKGPAKNWENVLLGLGVAGSAPGVEGEEIAPLAKENVAAP [SEQ ID 265] >gi|389620054|gb|AFK93486.1| granule-bound starch synthase [Hordeum vulgare subsp. vulgare] MAALATSQLATSGTVLGVTDRFRRPGFQGLRPRNPADAALGMRTIGASAAPKQSRKAHRGSRRCLSVVVRATGSGMNLVFVGAEMAPWSKTGGLGDVLGGLPAMAANGHRVMVVSPRYDQYKDAWDTSVISEIKVADEYERVRFFHCYK RGVDRVFIDHPWFLEKVRGKTKEKIYGPDAGTDYEDNQQRFSLLCQAALEAPRILNLNNNPYFSGPYGEDVVFVCNDWHTGLLLACYLKSNYQSNGIYRTAKVAFCIHNISYQGRFSFDFAQLNLPDRFKSSFDFIDGYDKPVEGRKINWM KAGILQADKVLTVSPYYAEELISDEARGCELDNIMRLTGITGIVNGMDVSEWDPTKDKFLAVNYDITTALEAKALNKEALQAEVGLPVDRKVPLVAFIGRLEEQKGPDVMIAAIPEILKEEDVQIILLGTGKKKFEKLLKSMEEKFPGKVRAVVRFNAPLAHQMMAGADLLAVTSRFEPCGLIQLQGMRYGTPCVCASTGGLVDTIVEGKTGFHMGRLSVDCNVVEPADVKKVATTLKRAVKVVGTPAYQEMVKNCMIQDLSWKGPAKNWEDVLLELGVEGSEPGIVGEEIAPLAMENVAAP [SEQ ID 266]

[0360] GLUC (Staphylococcus aureus) protein homologue 1 (SEQ ID 16) >gi|446599182|ref|WP_000676528.1| glutamyl endopeptidase [Staphylococcus aureus] >gi|253729369|gb|EES98098.1| trypsin [Staphylococcus aureus subsp. aureus TCH130] >gi|341844549|gb|EGS85761.1| glutamyl endopeptidase [Staphylococcus aureus subsp. aureus 21259] >gi|537390486|gb|AGU61109.1| Glutamyl endopeptidase precursor [Staphylococcus aureus subsp. aureus CN1] >gi|564714561|gb|ETD14665.1| glutamyl endopeptidase [Staphylococcus aureus subsp. aureus KPL1845] >gi|577466329|gb|EUG79766.1| glutamyl endopeptidase [Staphylococcus aureus M0139] >gi|580560623|gb|EVF84961.1| glutamyl endopeptidase [Staphylococcus aureus COAS6020] >gi|580687002|gb|EVH10169.1| glutamyl endopeptidase [Staphylococcus aureus UCIM6080] >gi|751815683|gb|KIN24957.1| glutamyl endopeptidase [Staphylococcus aureus MRSA_CVM43477] >gi|781884797|dbj|BAR08486.1| glutamyl endopeptidase precursor [Staphylococcus aureus subsp. aureus] >gi|781887762|dbj|BAR11210.1| glutamyl endopeptidase precursor [Staphylococcus aureus subsp.aureus]. MKGKFLKVSSLFVATLTTATLVSSSPAANALSSKAMDNHPQQSQSSKQQTPKIQKGGNLKPLEQREHANVILPNNDRHQITDTTNGHYAPVTYIQVEAPTGTFIASGVVVGKDTLLTNKHVVDATHGDPHALKAFPSAINQDNYPNGGFTAEQITKYSGEGDLAIVKFSPNEQNKHIGEVVKPATMSNNAETQVNQNITVTGYPGDKPVATMWESKGKITYLKGEAMQYDLSTTTGGNSGSPVFNEKNEVIGIHWGGVPNEFNGAVFINENVRNFLKQNIEDIHFANDDQPNNPDNPDNPNNPDNPNPDEPNNPDNPNNPDNPDNGDNDNSDNPDAA [SEQ ID 267]

Claims

1. A peptide consisting of the sequence of SEQ ID NO: 349, or an anti-inflammatory variant of said sequence, wherein said variant has one amino acid change compared to said sequence, and said amino acid change is selected from an amino acid insertion, addition, deletion and substitution.

2. The peptide of claim 1, which is chemically modified.

3. 3. The peptide of claim 2, which is chemically modified by modification of a side chain selected from an amino group, a guanidine group of an arginine residue, a carboxyl group, or a sulfhydryl group modification, incorporation of a protecting group selected from an N-terminal protecting group, a C-terminal protecting group, or a side chain protecting group, and incorporation during peptide synthesis of an unnatural amino acid and / or a derivative thereof selected from norleucine, 4-aminobutyric acid, 4-amino-3-hydroxy-5-phenylpentanoic acid, 6-aminohexanoic acid, t-butylglycine, norvaline, phenylglycine, ornithine, sarcosine, 4-amino-3-hydroxy-6-methylheptanoic acid, 2-thienylalanine, and / or a D-isomer of an amino acid.

4. A conjugate comprising a peptide according to any one of claims 1 to 3 conjugated, linked or fused to a binding partner.

5. The conjugate of claim 4, wherein the binding partner is selected from a molecular weight increasing compound selected from polyethylene glycol homopolymer or copolymer, monomethyl-substituted polymer of PEG (mPEG) and polyoxyethyleneglycerol (POG), a polyamino acid, or an antibody molecule.

6. A composition comprising a peptide according to any one of claims 1 to 3 or a conjugate according to claim 4 or 5.

7. The composition of claim 6 , wherein the composition is a powder.

8. 8. The composition of claim 6 or 7, which is a topical composition.

9. 9. The composition of claim 8, wherein the topical composition is selected from the group comprising creams, multiple emulsions, anhydrous compositions, aqueous dispersions, oils, milks, balsams, foams, lotions, gels, cream gels, hydroalcoholic solutions, hydroglycolic solutions, beauty products, personal care products, hydrogels, liniments, serums, soaps, dusting powders, pastes, semi-solid formulations, serums, shampoos, conditioners, ointments, optional rinse-off formulations, talc, mousses, powders, sprays, aerosols, solutions, suspensions, emulsions, syrups, elixirs, polysaccharide films, patches, gel patches, bandages, adhesive systems, water-in-oil emulsions, oil-in-water emulsions, and silicone emulsions.

10. 10. The topical composition of claim 8 or 9, comprising at least one cosmetically acceptable excipient.

11. 11. The topical composition of claim 10, wherein the at least one cosmetically acceptable excipient is a diluent, carrier, binder, lubricant, suspending agent, coating agent, preservative, stabilizer, dye, vehicle, solubilizer, base, emollient, emulsifier, fragrance, humectant, and / or surfactant.

12. The composition of any one of claims 6 to 11, which is a pharmaceutical composition, a cosmetic composition, or a personal care composition.

13. 13. The composition of claim 12, which is a personal care composition selected from creams, lotions, gels, hydrogels, ointments, shampoos, or serums.

14. A peptide according to any one of claims 1 to 3, a conjugate according to claim 4 or 5, or a composition according to any one of claims 6 to 13 for use in a method for the treatment or prevention of inflammation or an inflammatory disorder in a mammal.

15. 15. The peptide, conjugate or composition of claim 14, wherein the inflammatory disorder is selected from an inflammatory disorder of the skin, an inflammatory disorder of the joints, an inflammatory disorder of the cardiovascular system, an inflammatory disorder of the lungs or airways and an inflammatory disorder of the intestine.

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