Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
2000-07-20
2003-07-01
Russel, Jeffrey E. (Department: 1654)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S019300, C530S331000, C548S496000, C562S448000, C562S450000, C562S561000
Reexamination Certificate
active
06586403
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to peptides having anti-inflammatory properties. In particular, the present invention relates to peptides through actions on cells that modify the leukocyte recruitment and activation cascade and the actions of mediators released from inflammatory cells on target cells and tissues, including smooth muscle of animals, as well as humans.
BACKGROUND OF THE INVENTION
Immediate or Type 1 allergic reactions are largely attributed to IgE antibodies, although IgG antibodies can participate in and modulate allergic reactions. The allergy is generally caused by the activation of a subpopulation of immune cells, the mast cells and basophils. When antigen reacts with IgE antibody receptors on the cell's surface the chemical mediators initiate the allergic reaction by acting on adjacent immune, epithelial, endothelial and smooth muscle cells and promote, in a longer term, the influx of other inflammatory and immune cells (neutrophils, eosinophils, monocytes, lymphocytes) into tissue. This influx of inflammatory cells predisposes the patient to recurrent and sometimes delayed, or prolonged allergic or hypersensitivity reactions. A distinction between immediate and delayed allergic reactions and delayed, chronic immune injury can also be made. The Type 1 allergic reactions are defined according to the location where they occur. Asthmatic reactions occur in the lungs, rhinitis in the nose, conjunctivitis in the eyes, and atopic dermatitis in the skin, systemic allergic reactions in the circulation and intestinal reactions in the gastrointestinal system.
Asthma can be defined clinically as a condition of intermittent, reversible airways obstruction, and manifests itself as several clinical entities: allergic asthma, bronchial asthma, exercise induced asthma (EIA), chemical induced asthma, and status asthmaticus Asthma can be divided into two types. Extrinsic asthma is generally triggered by external agent such as allergens (dust mites, pollen, stings, drugs, or foods), and is commonly diagnosed in early life. Intrinsic asthma, which generally develops later in life, can be triggered by congested and inflamed tissues, infection, endogenous catecholamines (e.g. adrenaline), drugs (e.g. aspirin), stress or exertion.
Rhinitis, allergic conjunctivitis and atopic dermatitis are inflammations of the nasal mucosa, eyes and skin, respectively, often due to allergens such as pollen, dust or other airborne substances.
Anaphylactic shock, the most severe form of allergy, is a medical emergency. It is often severe and sometimes can provoke a fatal systemic reaction in a susceptible individual upon exposure to a specific antigen (as wasp venom or penicillin) after previous sensitization. Anaphylactic shock is characterized by respiratory symptoms, fainting, itching, urticaria, swelling of the throat or other mucous membranes and a sudden decline in blood pressure. Symptoms of anaphylactic shock include dizziness, loss of consciousness, laboured breathing, swelling of the tongue, blueness of the skin, bronchospasm, low blood pressure, and death.
Inflammatory response syndrome (IRS)—is an inflammatory response to a wide variety of clinical insults. IRS occurs as a result of extensive tissue damage and necrosis or the invasion of microorganisms, with the release of chemical mediators or cellular by-products such as the cytokines, lipid metabolites and autocoids. These mediators can be released in response to tissues and cells affected by infections, shock (endotoxemia, blood loss, blunt trauma), hypoxemia, radiation, bums, organ transplants, graft rejections. The proinflammatory IRS response is primarily responsible for the development of organ dysfunctions, such as acute lung injury, acute respiratory distress syndrome (ARDS), damage to gastrointestinal dysfunction (ileus, changes in permeability, pancreatitis like problems), and dysfunctions of the kidney, heart, liver and brain.
Amino Acids: Abbreviations, Letter Code and Linear Structure Formula.
Name
Abbr.
Linear structure formula
Alanine
Ala A
CH3—CH(NH2)—COOH
Arginine
Arg R
HN═C(NH2)—NH—(CH2)3—CH(NH2)—COOH
Asparagine
Asn N
H2N—CO—CH2—CH(NH2)—COOH
Aspartic acid
Asp D
HOOC—CH2—CH(NH2)—COOH
Cysteine
Cys C
HS—CH2—CH(NH2)—COOH
Cyclohexylalanine
Cha Cha
Cha-CH2—CH(NH2)—COOH
Glutamine
Gln Q
H2N—CO—(CH2)2—CH(NH2)—COOH
Glutamic acid
Glu E
HOOC—(CH2)2—CH(NH2)—COOH
Glycine
Gly G
NH2—CH2—COOH
Histidine
His H
NH—CH═N—CH═C—CH2—CH(NH2)COOH
Isoleucine
Ile I
CH3—CH2—CH(CH3)—CH(NH2)—COOH
Leucine
Leu L
(CH3)2—CH—CH2—CH(NH2)—COOH
Lysine
Lys K
H2N—(CH2)4—CH(NH2)—COOH
Methionine
Met M
CH3—S—(CH2)2—CH(NH2)—COOH
N-Methyl-phenylalanine
NMeF NMeF
CH3-Ph-CH2—CH(NH2)—COOH
Norleucine
Nle Nle
CH3—(CH2)3—CH(NH2)—COOH
Norvaline
Nval Nval
CH3—(CH2)2—CH(NH2)—COOH
Phenylalanine
Phe F
Ph-CH2—CH(NH2)—COOH
Phenylglycine
Phg Phg
Ph-CH(NH2)—COOH
Proline
Pro P
NH—(CH2)3—CH—COOH
Serine
Ser S
HO—CH2—CH(NH2)—COOH
Threonine
Thr T
CH3—CH(OH)—CH(NH2)—COOH
Tryptophan
Trp W
Ph-NH—CH═C—CH2—CH(NH2)—COOH
Tyrosine
Tyr Y
HO-p-Ph-CH2—CH(NH2)—COOH
Valine
Val V
(CH3)2—CH—CH(NH2)—COOH
L-amino acids are identified by capital letters (e.g. Tyr (Y)), whereas the corresponding D-isomeric form of the amino acid is identified by small letters (e.g. tyr (y)).
Salivary Gland Growth Factors, Hormones and Peptides: Regulation of Inflammation
Over the last few decades salivary gland growth factors (such as epidermal growth factor; EGF) have gained increased recognition as playing an important role in tissue repair. Another important feature of the actions of salivary gland factors, which can be growth factors and hormones, is the regulation of oral and systemic immune and inflammatory responses (Mathison et al, 1994). It is apparent that salivary gland involvement in regulating systemic immune and inflammatory responses is under the control of the sensory, sympathetic and parasympathetic nervous systems, as well as endocrine control from steroid control and peptide hormones. One aspect of nervous system regulation of the salivary glands involves the “cervical sympathetic trunk-submandibular gland (CST-SMG) axis” (Mathison et al, 1994; 1993), which is a distinct neuroendocrine system that is involved in regulating inflammatory responses and systemic homeostatic mechanisms (Ramaswamy et al., 1989; Mathison et al, 1995). The release of hormones from other salivary glands (e.g. parotid, sublingual, etc.) are also under the control of the nervous system.
Perturbation of the CST-SMG axis, by either performing a cervical sympathetic denervation or by removing the submandibular glands, results in an enhanced hypotensive response to intravenously administered endotoxin (Mathison et al, 1993). This observation led us to postulate the existence of factors within the salivary glands that modulate endotoxic hypotension, and we subsequently isolated a seven amino acid peptide (sequence=Thr-Asp-Ile-Phe-Glu-Gly-Gly SEQ ID NO.1; TDIFEGG submandibular gland peptide-T (SGP-T)), which at doses as low as 1 &mgr;g/kg inhibits lipopolysaccharide induced hypotension (Mathison et al, 1997b). Investigation of structure activity relationship has identified the C-terminal of SGP-T, the tripeptide FEG (Phe-Glu-Gly) and its D-isomer feG, also have significant anti-inflammatory activities (U.S. patent application Ser. No. 051/395). The biological activities of SGP-T, FEG Or feG include: a significant reduction in the severity of intermediate hypersensitivity reactions in the lung (Dery et al., 1999, 2000; Befus et al, 2000a,b,c), intestine (Mathison et al, 1997b,c; 1998), heart (Turesin et al, 2000) and the cardiovascular system (Mathison et al, 1997a, 1999b, 2000b; Davison et al, 2000), inhibition of neutrophil chemotaxis (Mathison et al, 2000a) and superoxide production (Nkemdirim et al, 1998).
Inflammation
Inflammation is a defense reaction caused by tissue damage or injury, characterized by redness, heat, swelling, and pain. Inflammation is the result of a response of the body's defense system that localizes and normally eradicates the irritant stimulus and
Mathison Ronald
Metwally Essam
Russel Jeffrey E.
Salpep Biotechnology Inc.
LandOfFree
Treating allergic reactions and inflammatory responses with... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Treating allergic reactions and inflammatory responses with..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Treating allergic reactions and inflammatory responses with... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3042190