WO2000072868A2

WO2000072868A2 - Peptides for therapeutic use

Info

Publication number: WO2000072868A2
Application number: PCT/IB2000/000895
Authority: WO
Inventors: Patrick T. Prendergast
Original assignee: Prendergast Patrick T
Priority date: 1999-06-01
Filing date: 2000-06-01
Publication date: 2000-12-07
Also published as: WO2000072868A3; AU5836700A

Abstract

The peptides have unique effects on the immuno system, resulting in their efficacy in a wide range of syndromes including: viral infections, autoimmune conditions, immune damage and/or disease progression in a patient suffering from one or more autoimmune condition, conditions associated with elevated Tumour Necrosis Factor (TNF), Interleukin 1 or 2 and/or Interferon. This can be achieved through the administration of therapeutic peptides disclosed herein, such as His-His-His-His-His-His-Glu-Ile-Cys-Pro-Ser-Phe-Gln-Arg-Val-Ile-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala, or one or more other compound which binds to antibody to Clara Cell protein, or one or more other compound which comprises one or more amino acid sequence which is sufficiently homologous to Clara Cell protein (as defined herein) that the compound provides properties similar to those described herein for Clara Cell protein.

Description

PEPTIDES FOR THERAPEUTIC USE

NOT FURNISHED AT TIME OF PUBLICATION

NOT FURNISHED AT TIME OF PUBLICAΗON

NOT FURNISHED AT TIME OF PUBLICATION

NOT FURNISHED AT TIME OF PUBLICAΗON

4973679, 4997927, 4415732, 4458066, 5047524, 4959463, 5212295, 5386023, 5489677, 5594121 , 5614622, 5624621 ; and PCT publication Nos. WO 92/07864, WO 96/29337, WO 97/14706, WO 97/14709, WO 97/31009, WO 98/04585 and WO 98/04575 all of which are incorporated herein by reference. The peptides described herein are suitable for linkage to oligonucleotides, which act as carrier molecules to, e.g., modulate the lipophilicity or pharmacokinetic properties of the peptides. Such linkages may be biologically labile to facilitate release of the peptide from the oligonucleotide once the conjugate has entered the patient.

As used herein, "autoimmunity" or an "autoimmune condition" includes conditions that have an autoimmune component such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis and other conditions disclosed herein.

Invention embodiments. The present invention relates to specific sub-unit therapeutic peptides, isolated from Clara cell protein, produced by either synthetic or recombinant methods and optionally subsequently modified (by, e.g., linkage to an adjunct residue), that display immuno-modulatory effects previously associated with native Clara cell protein. Herein the invention demonstrates that native Clara cell protein has no antiviral activity. However, the therapeutic peptides outlined herein demonstrate an ability to inhibit viral replication, as well as having immuno-modulatory activity. This modified peptide functions without the requirement of Clara cell receptors. The disclosed family of therapeutic peptides will have therapeutic benefits as immune modulators and anti- infective agents, e.g., anti-viral, anti-fungal or anti-bacterial agents.

It has been surprisingly shown that therapeutic peptides, monomer sequences have potent anti-viral activity. The peptides disclosed herein, have the same immuno modulatory effects of Clara cell protein, showing potent activity as monomers, but have enhanced efficacy, as they do not require the presence of Clara cell receptors to function. Accordingly, the disclosed therapeutic peptides (defined herein) when administered to human patients will have a broad immuno-modulatory effect, resulting in its application in many syndromes, particularly for previously unappreciated, antiviral properties in human patients. More specifically, one aspect of the present invention relates to the use of therapeutic peptides (defined herein) in treatment of and prophylaxis against viral infections, treatment of patients infected with a virus, reduction of the likelihood of viral infection in a patient who is at risk from suffering from a viral infection, reduction of the likelihood of septic shock caused by surgery, reduction of the likelihood of septic shock syndrome in a patient who is about to undergo surgery, prior to surgery, treatment of septic shock, treatment of autoimmune conditions, amelioration of immune damage and/or disease progression in a patient suffering from one or more autoimmune condition, treatment of different types of cancer, prophylaxis against cancer, reduction of the possibility of transplanted organ rejection, treatment of asthma, and treatment of a person whose immune system has been compromised, treatment of wasting syndrome, reducing the likelihood of wasting syndrome, treating cachexia, reducing the likelihood of cachexia, treating Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease, ameliorating immune damage and/or disease progression in a patient suffering from Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease, treating conditions associated with elevated Tumour Necrosis Factor (TNF), Interleukin 1 or 2 and/or Interferon, of reducing the possibility of pre-term labour, of treating inflammatory bowel disease and/or respiratory distress syndrome. The therapeutic peptides are also useful to ameliorate one or more symptoms of the conditions disclosed herein.

Furthermore, it is postulated that the use of peptides of this invention will induce the synthesis of inhibin, a secreted protein with tumor-suppressor activity. Peptides disclosed herein are envisaged to increase the expression of the programmed cell death (PCD) genes, testosterone repressed prostate message 2, Interleukin 1 -beta-converting enzyme (ICE), induce apoptosis and downregulate cyclins. These peptides are envisaged to play a major role in the long-lasting protection, similar to that experienced by full-term pregnancy, from chemically induced carcinogenesis. These peptides may also mimic the biological process of full-term pregnancy and provide lifetime reduction in breast cancer risk. It is envisaged that therapeutic use of the peptides disclosed herein will exhibit potent inhibition of prostaglandin-induced pre-term delivery. This will provide a potential therapy for pre-term labour inhibition in human pregnancy. These peptides will induce functional maturation of the cortical thymocytes. These peptides will act as a factor regulating antigen-independent differentiation of T-lymphocytes during pregnancy and accordingly enhance the immune system in embryogenesis. Thus, the peptides or formulations that contain them may be used effect any of these biological functions in a patient in need thereof.

In accordance with the present invention the pharmaceutical formulation of the therapeutic peptides (defined herein) can be defined as comprising at least one compound, comprising a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, conservative variants of SEQ ID NO. 1 to SEQ ID NO. 118,

SEQ ID NO. 122 to SEQ ID NO. 134 and conservative variants of SEQ ID NO. 122 to SEQ ID NO. 134. Terms such as "therapeutic peptides" and "the therapeutic peptides" as used herein includes these peptides.

In another embodiment the compound consists of at least one of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, a part of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, the part of a sequence having at least four amino acid residues, a conservative variant of a sequence selected from the group consisting of SEQ ID NO. 1 TO SEQ ID NO. 118, a conservative variant of a portion of a sequence selected from the group consisting of SEQ ID NO. 1 TO SEQ ID NO. 118, the portion of a sequence having at least four amino acid residues, a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134, a part of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 , the part of a sequence having at least four amino acid residues, a conservative variant of a sequence selected from the group consisting of SEQ ID NO. 122 TO SEQ ID NO. 134 and a conservative variant of a portion of a sequence selected from the group consisting of SEQ ID NO. 122 TO SEQ ID NO. 134, the portion of a sequence having at least four amino acid residues. Terms such as "therapeutic peptides" and "the therapeutic peptides" as used herein includes these peptides. As used herein phrases such as " the portion of a sequence having at least four amino acid residues", "a residue of a part of a peptide sequence" or "a residue of a conservative part of a peptide sequence" all mean that 4, 5, 6, 7, 8, 9 or 10 amino acid residues are present, typically about 10-80, often about 15-30 residues.

In another embodiment the compound consists of at least one of (1) a first residue consisting of: a residue of a peptide sequence selected from the group consisting of SEQ ID NO. 1 TO SEQ ID NO. 118, a residue of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 TO SEQ ID NO. 118, a residue of a conservative variant of a peptide sequence selected from the group consisting of SEQ ID NO. 1 TO SEQ ID

NO. 118, a residue of a conservative variant of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 TO SEQ ID NO. 118, a residue of a peptide sequence selected from the group consisting of SEQ ID NO. 122 TO SEQ ID NO. 134, a residue of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 122 TO SEQ ID NO. 134, a residue of a conservative variant of a peptide sequence selected from the group consisting of SEQ ID NO. 122 TO SEQ ID NO. 134 and a residue of a conservative variant of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 122 TO SEQ ID NO. 134 and (2) at least one adjunct residue, the at least one adjunct residue being attached to the first residue. Terms such as "therapeutic peptides" and "the therapeutic peptides" as used herein includes these peptides and peptide derivatives.

In another embodiment, the adjunct residue consists of one to eighty amino acids. In another embodiment, the adjunct residue consists essentially of positive charged amino acids. In another embodiment, the adjunct residue consists of one to twenty amino acids of positive charge. In another embodiment, the adjunct residue contains blocks of two or more adjacent amino acids of positive charge. In another embodiment, the positive charged amino acid is Histidine, Arginine and/or Lysine. In another embodiment, at least one compound consists of (1) a first residue consisting of the sequence that binds antibody to Clara cell protein; and (2) at least one adjunct residue, the at least one adjunct residue being attached to the first residue. In another embodiment, at least one compound consists of (1) a first residue consisting of the sequence that binds antibody to Clara cell protein; and (2) at least one adjunct residue containing at least one positively charged amino acid, the at least one adjunct residue being attached to the first residue.

The adjunct residues, in all of the embodiments described herein, can be placed at either end of the first residue, or at both ends, i.e., at the amino terminus and/or at the carboxyl terminus of the peptide to which it is bonded.

In another embodiment at least one compound consists of (1) a first residue consisting of a residue of a peptide sequence selected from the group consisting of SEQ ID NO. 1 TO SEQ ID NO. 118, a residue of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 TO SEQ ID NO. 118, a residue of a conservative variant of a peptide sequence selected from the group consisting of SEQ ID NO. 1 TO SEQ ID

NO. 118, a residue of a conservative variant of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 TO SEQ ID NO. 118, a residue of a peptide sequence selected from the group consisting of SEQ ID NO. 122 TO SEQ ID NO. 134, a residue of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 122 TO SEQ ID NO. 134, a residue of a conservative variant of a peptide sequence selected from the group consisting of SEQ ID NO. 122 TO SEQ ID NO. 134 or a residue of a conservative variant of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 TO SEQ ID NO. 134, and (2) at least one adjunct residue containing at least one positively charged amino acid, the at least one adjunct residue being attached to the first residue. Terms such as "therapeutic peptides" and "the therapeutic peptides" as used herein includes these peptides and peptide derivatives.

It has been surprisingly found that when positively charged amino acids are included within or are placed at the end of the adjunct residue, that targeting of the therapeutic peptides is enabled. In one embodiment at least one compound consists of the sequence, which binds to antibody to Clara cell protein.

In another embodiment, the therapeutic peptides are administered in their native, recombinant or synthetic forms.

In one embodiment the virus is human immunodeficiency virus (HIV). In another embodiment, the virus is a Kaposi's Sarcoma-associated herpes virus. In another embodiment, the virus is of the genus Molluscipoxvirus. In another embodiment, the virus is a cytomegalovirus. In another embodiment, the therapeutic peptides administered in a therapeutic, sustained-release form.

In another embodiment, the therapeutic peptide is administered alone or in conjunction with known anti-viral or immune altering therapeutics. In another embodiment, the therapeutic peptides are co-administered with a plasma-enhancing agent. In another embodiment, the therapeutic peptide is co- administered with Probenecid. In another embodiment, one or more of the therapeutic peptides are attached to a PEG molecule. In another embodiment, two or more of the therapeutic peptides are complexed together. In another embodiment, the products of the therapeutic peptide is produced within the patient by the transformation of patients own cells by the incorporation of the genetic code (DNA) or (RNA) for to allow endogenous synthesis of the therapeutic peptides (defined herein).

This includes sequences coding for therapeutic peptides containing positively charged amino acids at either end or both.

In another embodiment, the DNA coding for the therapeutic peptides is injected into the patients cells in situ (using current DNA vaccination) techniques without the need for in-vitro alteration and culture of the patients cells.

In another embodiment, virus is a DNA virus. In another embodiment, the virus is from the Influenza family of viruses.

The present invention also provides a pharmaceutical formulation for use in and/or a method of establishing a pro-hematopoietic activity in a patient, comprising administering to the patient at least one compound in an amount which is effective for the activity, the compound comprising a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, conservative variants of SEQ ID NO. 1 to SEQ ID NO. 118,

SEQ ID NO. 122 to SEQ ID NO. 134 and conservative variants of SEQ ID NO. 122 to SEQ ID NO. 134.

In one embodiment of the present invention there is provided a pharmaceutical formulation for use in and/or a method of treatment of the above-defined syndromes or diseases comprising the patient therapeutic peptides (defined herein) in an amount, which is effective for the treatment.

In one embodiment of the present invention there is provided a pharmaceutical formulation for use in and/or a method of treatment of the above-defined syndromes or diseases comprising administering to the patient the peptide comprising the sequence His- His-His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe-Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp- Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment in a pharmaceutically acceptable carrier. In another embodiment, the patient is a human. In another embodiment, the patient is an animal.

One useful property of the therapeutic peptides (defined herein) is their antiviral activity, which is manifested, pursuant to one aspect of the present invention, in a broad- spectrum anti-viral activity. Accordingly, the present invention contemplates administering daily to a subject an amount of therapeutic peptides (defined herein) that is clinically effective in treating or preventing a viral infection, which the subject suffers or is at risk from infection. Illustrative viruses against which the invention can be applied are HIV, cytomegalovirus (CMV), a KS-producing herpes virus, Kaposi's Sarcoma-associated herpes virus, the virus of the genus hepatitis, a virus of the genus Moliuscipoxvirus, togaviruses, flaviviruses, rubiviruses, pestiviruses, hantaviruses, among other viruses.

Pursuant to a preferred embodiment of the invention, the effective amount of therapeutic peptides (defined herein) thus administered is such as to produce a circulating concentration of therapeutic peptides (defined herein) sufficient to reduce viral loads as monitored by, e.g., viral titer methods or by PCR.

Treatment according to the present invention can be effected when the subject is a neonate. Administration is carried out prior to and/or at delivery.

The therapeutic peptides according to the present invention can be administered to a patient in any of a wide range of routes. Thus, with regard to the types of formulations in which the active compounds according to the present invention can be administered, as well as any additives can be included with the active compounds in the formulations, and the possible routes of administration, it is well known to those of skill in the art that such formulations can be provided in a wide variety of types, and it is within the skill of the ordinary artisans to select a specific formulation and route of administration and then test suitability for use. By way of example but not limitation, suitable routes include enteric, parenteral, topical, oral, rectal, nasal, buccal, pulmonary or vaginal routes. Parenteral routes include subcutaneous, intramuscular, intravenous, intraperitoneal, intradermal and sublingual administration. Also, compositions may be implanted into a patient or injected using a drug delivery system. The therapeutic peptides according to the present invention may be administered locally or systemically. By systemic administration means any mode or route of administration, which results in effective amounts of active ingredient appearing in the blood or at a site remote from the route of administration of the active ingredient.

Further, the therapeutic peptides according to the present invention may be administered intermittently. The advantage of this is that it allows the patient to suspend therapy for periods without the worry of inactivity of the drug resulting from the development of a resistant strain. The therapeutic peptides according to the invention may be formulated for enteral, parenteral or topical administration. Indeed all three types of formulations may be used simultaneously to achieve systemic administration of the active ingredient.

For oral administration, the compound can be formulated into solid or liquid preparations. Suitable formulations for oral administration include hard or soft gelatin capsules, dragees, pills, enterically coated formulations, tablets, including soft-coated tablets, troches, lozenges, melts, powders, micronized particles, non-micronized particles, solutions, emulsions, elixrs, suspensions, syrups or inhalations and controlled release forms thereof. In another embodiment of the invention, the enterically coated formulations are enterically coated beads or micropellets of the peptides incorporated into a common foodstuff or drink for ease and convenience of administration and increased compliance.

Solid dosage forms in addition to those formulated for oral administration include rectal suppositories. According to a further aspect of the invention the therapeutic peptides are administered in liposomes. The advantage of using liposome is there lipophillic properties. Additionally, the liposomes can be charged to target delivery.

Suitable injectable solutions include intravenous, subcutaneous and intramuscular injectable solutions. Examples of injectable forms include solutions, suspensions and emulsions. Typically the compound(s) is injected in association with a pharmaceutical carrier such as normal saline, Ringers solution, dextrose solution and other aqueous carriers known in the art. Appropriate non-aqueous carriers may also be used and examples include cyclodextrin, fixed oils, polyethylene glycol and ethyl oleate. A preferred carrier is 5% dextrose in saline. Frequently, it is desirable to include additives in the carrier such as buffers and preservatives or other substances to enhance isotonicity and chemical stability.

The therapeutic peptides can also be administered topically. Suitable formulations for topical administration include creams, drops (eye drops), gels, jellies, mucliages, pastes and ointments. The compounds may be formulated for transdermal administration, for example in the form of transdermal patches so as to achieve systemic administration.

The therapeutic peptides may also be administered in the form of an implant.

The therapeutic peptides may also be administered in the form of an infusion solution or as a nasal inhalation or spray.

In accordance with another aspect of the present invention, therapeutic peptides (defined herein) are provided in a therapeutic, sustained-release form, which is particularly well suited for implementing the aforementioned therapy. Representative examples of the above are nasal spray, transdermal patch, implant or suppository. These are further discussed below.

In another embodiment, the therapeutic peptides are incorporated in a pharmaceutically acceptable carrier, excipient, vehicle or the like for systemic administration by feeding. An example of such a carrier is cyclodextrin.

With regard to dosage and duration of treatment according to any aspect of the present invention, it is recognized that the ability of an artisan skilled in pharmaceutical administration of drugs to determine suitable dosages depending on many inter-related factors is well known, and skilled artisans are readily able to monitor patients to determine whether treatment should be started, continued, discontinued or resumed at any given time. For example, dosages of the compounds are suitably determined depending on the individual cases taking symptoms, age and sex of the subject and the like into consideration. The amount of the compound to be incorporated into the pharmaceutical composition of the invention varies with dosage route, solubility and chemical properties of the compound, administration route, administration scheme and the like. An effective amount for a particular patient may vary depending on factors such as the condition being treated, the overall health of the patient and the method route and dose of administration. The clinician using parameters known in the art makes determination of the appropriate dose. Generally, the dose begins with an amount somewhat less than the optimum dose and it is increased by small increments thereafter until the desired or optimum effect is achieved. Suitable dosages can be determined by further taking into account relevant disclosure in the known art.

In general, the amount of compound delivered to the patient is sufficient to achieve a plasma concentration of from about 3 to 10 μg/mL to about 5000 μg/mL of plasma, typically about 3 to about 50 μg/mL or about 5 to about 25 μg/mL. The effective amount is optionally administered in a dosage ranging between about 10 μg/kg and about 20,000 μg/kg of body weight of the patient. Unit dosages for any of the conditions described, e..g., in the embodiments or the claims, will typically comprise about 10-600 mg of a therapeutic peptide, often about 50-500 mg. In accordance with a preferred embodiment, the effective amount is such as to produce an elevation in T₈ count or T₄ count of at least about 10% over pre-treatment levels in the immunosuppressed patient after about one month of therapy, e.g., after about 4-12 weeks of therapy.

In one of its preferred aspects, the present invention discloses the therapeutic use of antiviral therapeutic peptide compounds. Specifically, the invention encompasses Protein 1 (defined herein) and antiviral therapeutic peptides, defined herein.

Protein 1 (P1) (SEQ ID NO:1), a low mol mass urinary Protein of previously unknown function, has been purified, sequenced and quantified from human biological fluids. The molecular size, subunit composition and partial amino acid sequence of P1 are similar to those of the 10 kDa Clara cell protein (CC10), a lung secretory protein. P1 is found in high concentrations in sputum, bronchoalveolar iavages, urine and semen of healthy individuals and in urine of pregnant women. The P1 or CC10 protein is not a specific and unique product of the lung, but like its homologue in rabbits (uteroglobulin) it is also present in urogenital secretions. It is proposed that P1 and CC10 may act as a natural immunosuppressor protecting the respiratory and urogenital tracts from unwanted inflammatory reactions.

Protein 1 (P1) is an alpha-microprotein, which was discovered in urine from patients with renal tubular dysfunction. P1 presents a sequence homology with rabbit uteroglobulin.

Clara cell protein has been described in the lung of rodents and humans. This small protein appears to be specifically and exclusively secreted by the Clara cells of bronchioles, hence its name Clara cell protein (CC10). P1 is similar in function to the Clara cell protein. CC10 is not a unique product of the lung but it also occurs in urogenital secretions.

A key aspect of the present invention is the fact that exogenous therapeutic peptides (defined herein) potentiate or intensify the effectiveness of the immune system. This "immune-potentiating" capability of the therapeutic peptides (defined herein) can be exploited to therapeutic advantage in a number of specific ways, which are illustrated in the following sections.

The present invention presents from this that levels of the therapeutic peptides, for example the 24 AA sequence plus 6 histidines (code Bel 16H), will be sufficient to suppress HIV transmission from mother to child. The invention also teaches that administering therapeutic peptides (defined herein) to achieve elevated blood levels would decrease viral load as well as prevent against HIV and other viral infections. The present invention also establishes that the therapeutic peptides (defined herein) have a direct antiviral effect in tissue culture (Figures 1-11 , tables 1-12, attached).

Administration of therapeutic peptides (defined herein) have a direct antiviral effect, as reported herein. This anti-viral effect is established by virtue of the ability of the therapeutic peptides (defined herein) to inhibit reverse transcriptase and p24 activity, as indicated in the accompanying graphs and tables. The therapeutic peptides (defined herein) are non-immunogenic, so antibodies are not produced in response to the presence the peptides in the patient. When a reverse transcriptase is inhibited, viral RNA is no longer able to copy itself into DNA and integrate itself into the genome of the infected cell. Similarly, the therapeutic peptides (defined herein) inhibit the reverse transcriptase enzyme of other retroviruses as well, inhibiting their propagation. It is postulated that administration of the therapeutic peptides (described herein) will cause a reduction in proviral DNA. Examples of viruses include, but are not limited to, human T-cell leukemia virus I (HTLV-I), which is indigenous to the Caribbean and to Israel, and human T-cell leukemia virus III (HTLV-III), which causes hairy cell leukemia.

In another embodiment of the invention, the patient is further administered at least one anti-viral compound and/or at least one immune altering compound. In another embodiment, the anti-viral compound is a protease inhibitor and/or a reverse transcriptase inhibitor. The present invention provides for the use of the therapeutic peptides for prophylaxis and/or treatment of retroviruses and togaviruses, including alphaviruses (also known as arboviruses, group A), flaviviruses (also known as arboviruses, group B)(such as yellow fever, as well as hepatitis C and hepatitis G), rubiviruses (also known as rubella viruses)(such as rubella) and pestiviruses, also known as mucosal disease viruses, such as bovine virus diarrhea virus (BVDV), using one or more of the compounds disclosed herein. Thus virus infections that may be treated include HIV, SIV, FIV, FELV, SHIV, Kaposi's Sarcoma-associated herpes virus and other herpesviruses (e.g., HSV-1 , HSV-2, human herpesvirus 6 (HHV-6) and HHV-8), the viruses of the genus Molluscipoxvirus, the viruses associated with hepatitis (HAV, HBV, hepatitis C virus [HCV]), and human cytomegalovirus, togaviruses and flaviviruses, e.g., California encephalitis virus, St. Louis encephalitis virus, western equine encephalitis virus, eastern equine encephalitis virus, Colorado tick fever virus, LaCrosse encephalitis virus, Japanese encephalitis virus, yellow fever virus, Venezuelan equine encephalitis virus, Murray valley fever virus, tick-borne encephalitis viruses, GB virus A, GB virus B, GB virus C, Dengue virus 1 , Dengue virus 2, Dengue virus 3, Dengue virus 4, Semliki Forest virus and Sindbis virus, rubiviruses, e.g., human rubella virus, pestiviruses, e.g., mucosal disease viruses such as bovine virus diarrhea virus, hog cholera virus and sheep border disease virus. The peptides are also useful to ameliorate one or more symptoms associated with viral infections, e.g., fever, pain or fatigue. Additionally, the therapeutic peptides (defined herein) may act like Peptide T, an octapeptide that blocks the gp-120 receptor for HIV on T-cells and neuronal cells. For example, administration of the therapeutic peptides (defined herein) according to the present invention could affect an increase in T cell levels in HIV-positive patients, initially for T₈ cells and thereafter for T₄ cells as well. Also, the therapeutic peptides directly suppress KS tumor survival and growth, and so patients with KS may require higher doses of therapeutic peptides to control both KS and HIV. Thus, a patient with both KS and HIV will require a large portion of therapeutic peptides (defined herein). Likewise, the presence in a patient of other concomitant viral infections or other immune problems would represent further therapeutic peptides (defined herein) requirement and, hence, would have to be considered in adjusting the therapeutic peptides (defined herein) dosage upward for optimal treatment of an infection of primary interest, such as HIV. Other variables will impact upon the essentially empirical endeavour of optimizing the therapeutic peptides (defined herein) dosage in the present invention. Accordingly, it is an aspect of the present invention that therapeutic peptide levels are optionally monitored, in conjunction with the observed indication of the infection being treated as well as of other therapeutic peptide requirements, to the end of maintaining therapeutic peptide plasma levels at least in the range of Clara cell protein seen in pregnant women (e.g., 6.2 μg/ml). The invention also teaches that in certain cases, an interruption of therapy or a decrease in therapeutic peptides (defined herein) dosage results in a decline in T cell counts and clinical status. Accordingly, longer-term administration of therapeutic peptides (defined herein), continuing for months or even years, is preferred. To this end, and to allow for adjustments needed to achieve and maintain the in vivo levels of therapeutic peptides (defined herein) that characterize the present invention, the use of therapeutic peptides (defined herein) in a sustained-release modality represents a preferred approach. One sustained-release form is a transdermal therapeutic peptides (defined herein) patch, after the fashion of the DURAGESIC™ fentanyl patch. In this context, transdermal delivery of proteins like therapeutic peptides (defined herein) has been accomplished iontophoretically or electroosmotically, i.e., under the influence of an electric field. See, for example, U.S. Pat. No. 4,878,892, No. 4,940,456, No. 5,032,109, No.5, 158,537 and No. 5,250,023. The respective contents of these documents, as well as of the other publications cited in the present specification, are hereby incorporated by reference.

Another sustained-release form within the present invention is an implantable therapeutic peptides (defined herein) delivery system. In the manner of the NORPLANT™ levonorgestrel implant, a type of device in this category employs passive release of therapeutic peptides (defined herein) through a non-biodegradable, rate-limiting membrane element composed, for instance, of a hydrogel or a microporous polymer. See U.S. Pat. No. 5,292,515 and patent documents cited there, such as U.S. Pat. No.3,993,072, and U.S. Pat. No. 4,959,217. Another type of implant contemplated by the present invention incorporates a pump function to administer the peptide. See, for instance, U.S. Pat. No. 5,030,216, No.5,368,588, No. 5,370,635 and No. 5,391 ,164. The pumping action can be osmotically driven or patient-activated, for example, or can be controlled by a servomechanism which allows for the "titration" of peptide and, hence, dosage adjustment in light of monitored parameters, such as therapeutic peptides (defined herein) and the clinical symptoms of the condition under treatment.

KS is a malignancy that will respond to the therapeutic peptides and clinically effective doses of therapeutic peptides (defined herein), i.e., doses effective in causing tumor regression, are expected to be relatively well tolerated. In particular, at least partial remission of KS should occur when serum levels of the therapeutic peptides are achieved similar to Clara cell protein levels observed in women during pregnancy.

The advantages associated with therapy according to the present invention are several. There should be no evidence of development of a flu-like syndrome seen with alpha-interferon therapy, for example. Peripheral neuropathy, cardiac compromise, gastrointestinal upset, alopecia, myelosuppression, and pulmonary fibrosis associated with administration of vincristine sulfate, doxorubicin, and bleomycin sulfate also should not occur. Radiation-associated burns and secondary infections would also be avoided. Thus, one would expect significantly fewer complications associated with a protocol based on a therapeutic peptide, pursuant to the present invention, than are normally associated with conventional therapy in these areas.

In accordance with the present invention, therefore, therapeutic peptides (defined herein) will be useful in controlling molluscum, not only in AIDS patients but also in any immune-compromised patient. Illustrative of such patients are transplant recipients, individuals receiving chemotherapy, dialysis patients, elderly persons, diabetics, and patients with a congenitally underdeveloped or defective immune system.

Cytomegalovirus. Morphologically and structurally similar to other human herpes viruses, CMV causes a vision-threatening retinitis in AIDS patients. CMV retinitis has been treated with gancyclovir and/or foscamet, but with only limited success.

There is provided prophylaxis and/or treatment of CMV-induced retinitis, whereby CMV-induced retinitis responds to therapeutic peptides (defined herein) treatment. Thus, the present invention further contemplates that therapeutic peptides (defined herein) will synergize with other treatment modalities, such as gancyclovir or foscamet, in the treatment of CMV-induced retinitis.

According to this invention, therapeutic peptides (defined herein) also will be used in the context of adjunctive therapy, in preparation for transplantation and other medical interventions, which place a patient at risk for systemic life-threatening CMV infection. In addition, it is understood that therapeutic peptides (defined herein) will be useful therapeutically after CMV infection has occurred. Support for using therapeutic peptides in this regard is found in the observation that CMV infection is almost never active at the time of delivery of a baby, when Clara cell protein levels are high. One example of a suitable formulation for use in treatment of CMV is a daily dosage of 140 mg of SEQ ID NO: 134 in saline for 5 days. Neonatal Applications. As noted above, Clara cell protein is found in high concentration in the amniotic fluid during pregnancy and is believed to act as a natural immune-potentiator. Clara cell protein is also produced in the fetal lungs. By the same token, it is a further aspect of the present invention that therapeutic peptides (defined herein) will be administered to a baby at or prior to delivery and, optionally, for the first several months of life as well, in order to prevent HIV transmission and control any low- level viremia. (Compare suggestion by Connor et al., N. Eng. J. Med. 331 : 1173-89 (1994), to give the anti-HIV drug, zidovidine, during the last trimester of pregnancy and during delivery to impede HIV transmission from mother to child.) Moreover, the inventive therapeutic peptides (defined herein) therapy can be effected neonatally to protect against various other viruses, including herpes viruses, such as CMV, and oncogenic viruses. There is further included in the present invention, prophylaxis and treatment of cancer. In one embodiment the cancer is selected from the group consisting of breast cancer, colon cancer, leukaemia, brain cancer, lung cancer, KS, melanomas and any viral originated cancers.

Sepsis - septic shock. Sepsis occurs when gram negative bacteria and endotoxins or complex lipolysaccharides enter the blood stream. Their compounds, normal components of the bacterial cell wall, induce a massive inflammatory host response or "sepsis cascade". This cascade is mediated by cytokines such as TNFOC and Interleukins 1 , 2 and 8. By prophylacticaliy administering to a patient a suitable amount of P1 protein, the bacterial and endotoxic products would be prevented from initialising the cytokine cascade, which results in septic shock. In the case of prevention of sepsis, it would be well within the skill of those of skill in the art to determine a suitable length of time prior to surgery, e.g., from one hour to 12 hours or more, so long as the levels of active ingredient are elevated at the time or surgery and for at least 12 hours following surgery, preferably about 36 hours to about 7 days following surgery, for performing the prophylaxis. Five hundred thousand cases of sepsis occur annually in the U.S. and about 1.4 million cases worldwide. One-third of patients die within 30 days and nearly 50% die within six months. Estimates for treatment cost range from $5 billion to $10 billion dollars annually. Autoimmune Diseases. It now is recognized that many autoimmune diseases occur as a consequence of immune misdirection as a result of viral, bacterial or fungal infections. Among such diseases are rheumatoid arthritis, multiple sclerosis (MS) and ulcerative colitis, all of which are known to remit during pregnancy and flare at delivery or tissue injury. Other autoimmune diseases, for which no viral etiology has been described, such as uveitis and psoriasis, likewise remit during pregnancy and flare at delivery. Accordingly, the present invention encompasses the use of therapeutic peptides, to achieve blood levels at least comparable to Clara cell protein levels typically seen in a mother during pregnancy, to control autoimmune diseases in adults.

Prophylactic Applications. According to another aspect of the present invention, therapeutic peptides will be administered prophylactically, to persons-medical personnel, transplant recipients, blood recipients, hemophiliacs, sexually active individuals, and HIV- negative recreational drug users, for instance-who are deemed at risk of exposure to HIV or who may have been exposed already to the virus. Prophylactic application of Therapeutic peptides also could benefit others who are at risk from disease, such as (i) travellers to areas affected epidemically by other, life-threatening viruses, such as HTLV-I and Ebola virus. More generally, Therapeutic peptides could be administered, in "rescue" fashion, immediately after a possible exposure to a variety of illnesses, the impact of which could be ameliorated by the direct antiviral effect of the therapeutic peptides together with its immuno-T-cell specific suppressive characteristics. Therapeutic peptides may be administered to treat or prevent leprosy where autoimmune attack by T-cells is a major negative pathogenic factor. Furthermore, when viral infections erupt for which there is no therapy or even a known etiology, as was the case in central Africa with the Ebola virus and in the southwestern United States with the hantavirus, uninfected individuals would have recourse to the therapeutic peptides therapy, in the reasonable hope that it will stop the particular virus involved, and infected patients also would be treated in an attempt to control the virus. Immune-System Remediation. The present invention comprehends treatment of individuals with therapeutic peptides in instances where the immune system has been compromised or is to undergo compromise. Persons who could be treated in this context include, for example, cancer patients who are to start chemotherapy or irradiation, which is expected to weaken or otherwise jeopardize their immune systems. In appropriate formulations that are known and conventional to those skilled in the art, the administration of Therapeutic peptides by various routes of administration is contemplated, including intramuscular subcutaneous, transmucosal, transdermal and parenteral. As discussed above, administration of therapeutic peptides is contemplated through a sustained-release drug delivery system, for example, transdermal skin patches and different types of implants. A bioavailable, sustained-release oral formulation of therapeutic peptides also should be possible. Furthermore, the therapeutic peptides can be produced synthetically or from a recombinant cell line. In another embodiment, the recombinant cell line is a mammalian cell line, an insect cell line or a bacterial cell line. It should be understood that this detailed description, while indicating preferred embodiments of the invention, are given by way of illustration. Various changes and modifications within the spirit and scope of the invention will be apparent to those skilled in the art from the description. In the present specification and claims, the expression "part", when used in connection with a sequence, means a string of consecutive adjacent amino acid residues in a particular sequence, e.g., the first through fourth amino acid in a sequence which has four or more amino acid residues, the third through ninth amino acid residues in a sequence which has nine or more amino acid residues, the second through fifth amino acid residues in a sequence which has 265 amino acid residues, etc.

In the present specification and claims, the expression "residue", e.g., a residue of a compound, refers to the chemical structure which would be obtained if at least one atom (e.g., a hydrogen atom) were removed from the compound to create a free radical-at the site of the compound from which the at least one atom has been removed, the residue may or may not be bonded to another residue

In the present specification and claims, the expressions "comprising" and "comprises" are used in accordance with their normal usage to mean that the definition covers all articles or processes which include the recited element(s) and/or feature(s), and which may or may not include one or more additional element(s) and/or feature(s) which are not recited. For example, an expression that a compound "comprises" an amino acid residue of a particular sequence (AA)_n is satisfied by compounds: which consist of only polypeptide sequence (AA)_n; and which include a residue of (AA)_n and one or more additional chemical group, e.g., an adjunct group (e.g., selected from (1) a peptide sequence residue comprising at least one amino acid residue, (2) a sugar residue, (3) a fatty acid residue and (4) a nucleotide sequence residue comprising at least one nucleotide residue), the group being attached to the polypeptide sequence (AA)_non one or both of the C-terminal and/or N-terminal groups in the sequence (AA)_n.

In a further embodiment, the sugar residue consists of heparin. In another embodiment, the fatty acid residue is selected from the group consisting of d - C₂₀ fatty acid. In another embodiment the fatty acid is diphosphatidyl choline.

Throughout the present specification, where a compound is referred to as "consisting of an amino acid sequence defined by a series of amino acid residues, it is to be understood that the compound includes no further amino acid residues and no adjunct residue may include an amino group and a carboxy group at the N-terminal and C-terminal ends, respectively, of the sequence.

In like manner and with similar effects, the present invention is further directed to methods of treating or preventing conditions as described above, wherein, a patient is administered one or more compound which comprises a therapeutic peptide sequence selected from the group consisting of SEQ ID NO:1 - SEQ ID NO:118 and conservative variants (defined below) of SEQ ID NO:1 - SEQ ID NO:118. SEQ ID NO:1 - 147 are set forth in the attached "Sequence Listing", which is a part of the disclosure in the present application. The sequences set forth in SEQ ID NO:1 - SEQ ID NO:118 have sufficient homology and/or identity of key amino acid residues in key locations that all compounds which comprise or consist of residues of such amino acid sequences would be expected by those skilled in the art to exhibit, to varying degrees, the properties described herein as being exhibited by Clara Cell Protein .

Likewise, other naturally occurring compounds exist (such as rabbit uteroglobin, the structure of which is well known by those of skill in the art) which comprise residues of amino acid sequences having sufficient homology and/or key amino acid residues in key locations that they exhibit, to varying degrees, the properties described herein as being exhibited by Clara cell protein. According to the present invention, therefore, such compounds, and residues and/or derivatives (i.e., where one or more chemical group is replaced with a different organic group) of such compounds can be used.

As used herein, the expression "SEQ ID NO: 1 - SEQ ID NO: 118 and SEQ ID NO: 122 - SEQ ID NO: 134" refers to the group consisting of the following 131 sequences: SEQ ID NO: 1 , SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 , SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21 , SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31 , SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41 , SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51 , SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81 , SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91 , SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101 , SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111 , SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131 , SEQ ID NO:132, SEQ ID NO: 133, SEQ ID NO: 134. In like manner, other expressions of ranges of numbers of SEQ ID NO'S are meant to be inclusive of all sequences having an ID NO that falls inside or at the end of the recited range. The expression "conservative variation" with respect to a particular compound, as used herein, includes functionally equivalent salts of the compound, functionally equivalent derivatives of the compound, and functionally equivalent muteins of the compound. As used herein a "mutein" of a compound refers to analogues of the compound in which one or more of the amino acid residues of the compound, such as 1-15, preferably 1-10 (e.g., 7) and more preferably 1-5 residues or even only a single residue, differ from, are added to or are deleted from the compound, without changing considerably the property, e.g., antiviral activity, of the resulting product. These muteins are prepared by known synthesis and/or site-directed mutagenesis techniques, or any other known technique suitable therefore. The substitutions are preferably conservative. See, e.g., Schulz, G. E. et al., Principles of Protein Structure, Springer- Verlag, New York, 1978, and Creighton, T. E.,

Proteins: Structure and Molecular Properties, W. H. Freeman & Co., San Francisco, 1983, which are hereby incorporated by reference.

Examples of conservative variations include the substitution of one hydrophobic residue such as isoleucine, valine, leucine or methionine for another, or the substitution of one polar residue for another, such as the substitution of arginine for lysine, glutamic for aspartic acids, or glutamine for asparagine, and the like. The term "conservative variation" implies sequence - conservation or function - conservative variants.

The types of such substitutions which may be made in the protein or peptide molecule of the present invention may be based on analysis of the frequencies of amino acid changes between a homologous protein of different species, such as those presented in Table 1-2 of Schulz et al. (supra) and FIGS. 3-9 of Creighton (supra). Based on such an analysis, conservative substitutions may be defined herein as exchanges within one of the following five groups: 1. Small aliphatic, nonpolar or slightly polar residues: ala, ser, thr (pro, gly); 2. Polar, negatively charged residues and their amides: asp, asn, glu, gin; 3. Polar, positively charged residues: his, arg, lys;

4. Large aliphatic, nonpolar residues: met, leu, ile, val (cys); and 5. Large aromatic residues: phe, tyr, trp.

The three amino acid residues in parentheses above have special roles in protein architecture. Gly is the only residue lacking any side chain and thus imparts flexibility to the chain. Pro, because of its unusual geometry, tightly constrains the chain. Cys can participate in disulfide bond formation, which is important in protein folding. Note that Schulz et al. would merge Groups 1 and 2, above. Note also that Tyr, because of its hydrogen bonding potential, has some kinship with Ser, Thr, etc.

Conservative amino acid substitutions according to the present invention, e.g., as presented above, are known in the art and would be expected to maintain biological and structural properties of the polypeptide after amino acid substitution. Most deletions and insertions, and substitutions according to the present invention are those, which do not produce radical changes in the characteristics of the protein or peptide molecule. One skilled in the art will appreciate that the effect of substitutions can be evaluated by routine screening assays, either immunoassays or bioassays. For example, a mutant typically is made by site-specific mutagenesis of the peptide molecule-encoding nucleic acid, expression of the mutant nucleic acid in recombinant cell culture, and, optionally, purification from the cell culture, or a biological sample containing a suitable protein, for example, by immunoaffinity chromatography using a specific antibody on a column (to absorb the mutant by binding to at least one epitope).

The term "fused protein" refers to a polypeptide or a mutein thereof fused with another protein which has an extended residence time in body fluids. The compounds according to the invention may thus be fused to another protein, polypeptide or the like, e.g., an immunoglobulin or a fragment thereof.

The term "salts" herein refers to both salts of carboxyl groups and to acid addition salts of amino groups of the compounds of the invention, muteins and fused proteins thereof. Salts of a carboxyl group may be formed by means known in the art and include inorganic salts, for example, sodium, calcium, ammonium, ferric or zinc salts, and the like, and salts with organic bases as those formed, for example, with amines, such as triethanolamine, arginine or lysine, piperidine, procaine and the like. Acid addition salts include, for example, salts with mineral acids such as, for example, hydrochloric acid or sulfuric acid, and salts with organic acids such as, for example, acetic acid or oxalic acid. "Functional derivatives" as used herein cover derivatives of the compounds of the invention, and their fused proteins and muteins, which may be prepared from the functional groups which occur as side chains on the residues or the N- or C-terminal groups, by means known in the art, and are included in the invention as long as they remain pharmaceutically acceptable, i.e. they do not destroy the activity of the protein and do not confer toxic properties on compositions containing it. These derivatives may, for example, include polyethylene glycol side-chains which may mask antigenic sites and extend the residence of the compounds of the invention in body fluids. Other derivatives include aliphatic esters of the carboxyl groups, amides of the carboxyl groups by reaction with ammonia or with primary or secondary amines, N-acyl derivatives of free amino groups of the amino acid residues formed with acyl moieties (e.g. alkanoyl or carbocyclic aroyl groups) or acyl derivatives of free hydroxyl groups (for example that of seryl or threonyl residues) formed with acyl moieties. The term "functional derivative" also includes proteins which have an amino acid sequence longer or shorter than the sequence determined, as long as the protein still has the ability to perform the desired function. As "active fractions" of the compounds of the invention, their fused proteins and their muteins, the present invention covers any fragment or precursors of the polypeptide chain of the protein molecule alone or together with associated molecules or residues linked thereto, e.g., sugar or phosphate residues, or aggregates of the protein molecule or the sugar residues by themselves, provided said fraction has the ability to provide the desired function, e.g., inhibit viral infection. Such active fractions can be readily determined by testing smaller and smaller portions of the compound or mutein to find the smallest fragment which retains the ability to inhibit viral infections. Any fractions containing the smallest active fraction will also be an active fraction. Undue experimentation would not be involved as the required tests for antiviral activity (as described herein) may be routinely carried out. The present invention also related to pharmaceutical formulations for use in and/or methods of prophylaxis and treatment, for which the conditions discussed above are applied, comprising administering to said patient at least one compound comprising a peptide sequence which binds to antibody to clara cell protein. The peptide sequence can be selected from therapeutic peptide sequences defined within. Those of skill in the art are readily able to determine whether a given sequence binds to antibody to clara cell protein. As mentioned above, the present invention further relates to pharmaceutical formulations for use in and/or methods of prophylaxis and treatment for which the conditions discussed above are applied, in which DNA (e.g., any of the sequences SEQ ID NO:119 to SEQ ID NO:121 or SEQ ID NO:135 to SEQ ID NO:147 or DNA to code for any of SEQ ID NO: 1-118 or SEQ ID 122-134), is incorporated (e.g., by being injected) into at least one of patient's cells, whereby patient's body produces any one of SEQ ID NO:1 - SEQ ID NO:118 or SEQ ID NO: 122 - SEQ ID NO: 134, (e.g., therapeutic peptide: 24 AA sequence plus 6 histidines (code Bel 16H, SEQ ID NO: 134)) or any compounds as disclosed herein for use in treatment or prophylaxis of one or more condition. Other known methods include methods in which DNA is injected, e.g., within gold, into a patients muscle, or powder jet injection.

The present invention further relates to a pharmaceutical formulation for use in and/or method of treatment of and prophylaxis against viral infections, treatment of patients infected with a virus, reduction of the likelihood of viral infection in a patient who is at risk from suffering from a viral infection, reduction of the likelihood of septic shock caused by surgery, reduction of the likelihood of septic shock syndrome in a patient who is about to undergo surgery, prior to surgery, treatment of septic shock, treatment of autoimmune conditions, amelioration of immune damage and/or disease progression in a patient suffering from one or more autoimmune condition, treatment of different types of cancer, prophylaxis against cancer, reduction of the possibility of transplanted organ rejection, treatment of asthma, and treatment of a person whose immune system has been compromised, treatment of wasting syndrome, reducing the likelihood of wasting syndrome, treating cachexia, reducing the likelihood of cachexia, treating Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease, ameliorating immune damage and/or disease progression in a patient suffering from Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease, treating conditions associated with elevated Tumour Necrosis Factor (TNF), Interleukin 1 or 2 and/or Interferon, of reducing the possibility of pre-term labour, of treating inflammatory bowel disease and/or respiratory distress syndrome, comprising administering to said patient therapeutic peptides (defined herein), said therapeutic peptides being contained within a cage, e.g., a cage which comprises microporous Nylon ™. The present invention further provides assays in which polyclonal antibody to Clara cell protein is administered, with or without adjuvant, in order to determine whether the antibody would work.

The present invention also provides methods of administering therapeutic peptides to an animal with adjuvant, whereby the animal generate antibodies to the protein, which can be isolated by taking blood from the animal and running the blood through a column to which the therapeutic peptides have been attached.

The present invention also includes in a preferred aspect, administering two or more amino acid sequences, e.g. a pair of amino acid sequences having around 24 amino acid residues, the two sequences (1) mixed together iin a formulation or a composition or (2) interacting with one another through hydrogen bonding and/or electrostatic interaction and present in a formulation or a composition.

Note that SEQ ID NOS 135-147 are DNA sequences of human origin, and specifically are fragments of human CC10 protein. Note further that the present invention includes not only the proteins, peptides, and polynucleotides specifically disclosed, but also those including conservative substitutions; e.g., replacement of one charged, basic, acidic, hydrophyllic, or hydrophobic amino acid (or codon therefor) with another charged, basic, acidic, hydrophyllic, or hydrophobic amino acid (or codon therefor). The invention also includes purified and isolated versions of the specified proteins, peptides, and polynucleotides. Preferred purified versions are at least about 0.1% or 1% pure, more preferably 5, 10, or 15% pure, and most preferably 20, 25, 30, 40, 50% or more pure (i.e., separated from nonaqueous impurities, other than pharmaceutically acceptable diluents, excipients, and carriers). Isolated versions are substantially removed from their natural environment; i.e., separated from the majority of substances with which they conjointly occur in nature.

The polynucleotides of the present invention can advantageously be placed under the control of an indicible or constituitive promoter. They can be used as naked DNA, injected or otherwise administered to produce expression of the encoded polypeptide, or they can alternatively be used in viral vectors, host cells or other suitable vectors.

The numbered embodiments are provided below further exemplify the invention and aspects thereof.

1. A pharmaceutical formulation, comprising an excipient and at least one compound, said compound comprising a peptide sequence selected from the group consisting of: SEQ ID NO. 1 to SEQ ID NO. 118, conservative variants of SEQ ID NO. 1 to SEQ ID NO. 118, SEQ ID NO. 122 to SEQ ID NO. 134 and conservative variants of SEQ ID NO. 122 to SEQ ID NO. 134.

2. The pharmaceutical formulation as embodimented in embodiment 1 , wherein said compound consists of at least one of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, a part of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, the part of a sequence having at least four amino acid residues, a conservative variant of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, a conservative variant of a portion of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, the portion of a sequence having at least four amino acid residues, a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134, a part of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134, the part of a sequence having at least four amino acid residues, a conservative variant of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 or a conservative variant of a portion of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134, the portion of a sequence having at least four amino acid residues.

3. The pharmaceutical formulation as embodimented in embodiment 1 , wherein said compound consists of at least one of: a first residue consisting of: a residue of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a conservative variant of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a conservative variant of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; a residue of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; a residue of a conservative variant of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 or a residue of a conservative variant of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; and at least one adjunct residue, said adjunct residue being attached to the first residue.

4. The pharmaceutical formulation as embodimented in embodiment 3 wherein the adjunct residue consists of one to eighty amino acids. 5. The pharmaceutical formulation as embodimented in embodiments 3 or 4 wherein the adjunct residue consists of at least one positive charged amino acid.

6. The pharmaceutical formulation as embodimented in embodiments 3 to 5 wherein the adjunct residue consists of one to twenty amino acids of positive charge.

7. The pharmaceutical formulation as embodimented in embodiments 3 to 6 wherein the adjunct residue contains blocks of two or more adjacent amino acids of positive charge.

8. The pharmaceutical formulation as embodimented in embodiments 3 to 7 wherein the positive charged amino acid is either histidine, arginine and/or lysine. 9. The pharmaceutical formulation as embodimented in embodiment 3 to 8, wherein the adjunct residue is selected from the group consisting of (1) a peptide sequence residue comprising at least one amino acid residue, (2) a sugar residue, (3) a fatty acid residue and (4) a nucleotide sequence residue comprising at least one nucleotide residue. 10. The pharmaceutical formulation as embodimented in embodiment 9, wherein the sugar residue consists of heparin.

11. The pharmaceutical formulation as embodimented in embodiment 9, wherein the fatty acid residue is selected from the group consisting of Ci to C₂₀ fatty acid.

12. The pharmaceutical formulation as embodimented in embodiment 11 , wherein the fatty acid residue consists of diphosphatidyl choline.

13. The pharmaceutical formulation as embodimented in embodiments 3 to 11 , wherein the adjunct residue is covalently bonded to the first residue at a C-terminal or an N-terminal end of the first residue.

14. The pharmaceutical formulation as embodimented in any one of embodiments 1 to 13, wherein the peptide sequence residue consists of albumin, lactoferrin, alpha fetoprotein, urinary protein, urinary protein 1 and or uteroglobin. 15. The pharmaceutical formulation as embodimented in any one of embodiments 1 to 14, wherein the compound is administered to the patient in plasma, the compound being present in the plasma in a concentration of from about 10 to about 5000μg of the compound per ml of plasma. 16. The pharmaceutical formulation as embodimented in any one of embodiments 1 to 15, wherein the compound is administered to the patient in a dosage in the range of from about 10 μg to 20,000 μg per kilogram of body weight of the patient.

17. The pharmaceutical formulation as embodimented in any one of embodiments 1 to 16, wherein the patient is a neonate and the administering is effected prior to delivery of the neonate and/or during delivery of the neonate.

18. The pharmaceutical formulation as embodimented in any one of embodiments 1 to 17, wherein the peptide sequence is produced synthetically or is produced from a recombinant cell line.

19. The pharmaceutical formulation as embodimented in embodiment 18, wherein the recombinant cell line is a mammalian cell line, an insect cell line or a bacterial cell line.

20. The pharmaceutical formulation as embodimented in any one of embodiments 1 to 19, further omprising administering to the patient at least one anti-viral compound and/or at least one immune altering compound. 21. A pharmaceutical formulation as embodimented in embodiment 20, wherein the anti-viral compound is a protease inhibitor and/or a reverse transcriptase inhibitor.

22. The pharmaceutical formulation as embodimented in any one of embodiments 1 to 21 , wherein the patient is a human.

23. The pharmaceutical formulation as embodimented in any one of embodiments 1 to 21 , wherein the patient is an animal.

24. The pharmaceutical formulation as embodimented in any preceding embodiment wherein the compound is co-administered with Probenecid

25. The pharmaceutical formulation as embodimented in any preceding embodiment wherein the compound is attached to a PEG molecule. 26. The pharmaceutical formulation as embodimented in any preceding embodiment wherein at least two or more of the compounds are present in the formulation or they are complexed together.

27. The pharmaceutical formulation as embodimented in any preceding embodiment wherein at least one compound binds antibody to clara cell protein. 28. The pharmaceutical formulation as embodimented in any preceding embodiment, wherein the composition is administered enterically, parenterally, topically, orally, rectally, nasally or vaginally. 29. The pharmaceutical formulation as embodimented in any preceding embodiment, wherein the composition is administered intermittently.

30. The pharmaceutical formulation as embodimented in any preceding embodiments, wherein compound is administered in a therapeutic, sustained-release form.

31. A pharmaceutical formulation as embodimented in any preceding embodiment further comprising administering an adjuvant to said patient.

32. The pharmaceutical formulation as embodimented in any preceding embodiment for use in treating viral infection comprising administering to the patient at least one compound in an amount which is effective for the treatment.

33. The pharmaceutical formulation as embodimented in embodiment 32, wherein the virus is selected from the group consisting of HIV, Kaposi's Sarcoma- associated herpes virus, the viruses of the genus Molluscipoxvirus, the viruses of the genus hepatitis, and cytomegalovirus. 34. The pharmaceutical formulation for use in treating viral infection as embodimented in embodiment 32 or 33 wherein the virus is selected from the group consisting of togaviruses, flaviviruses, rubiviruses, pestiviruses and hantaviruses.

35. The pharmaceutical formulation as embodimented embodiments 1 to 32 for use in reducing the likelihood of viral infection in a patient who is at risk for suffering viral infection comprising administering to the patient at least one compound in an amount which is effective for the treatment.

36. The pharmaceutical formulation as embodimented embodiments 1 to 32 for use in reducing the likelihood of septic shock syndrome in a patient who is about to undergo surgery comprising administering to the patient, shortly before the surgery is performed, at least one compound in an amount which is effective for the treatment.

37. The pharmaceutical formulation as embodimented embodiments 1 to 32 for use in treating septic shock syndrome in a patient who has recently undergone surgery comprising administering to the patient, at least one compound in an amount which is effective for the treatment. 38. The pharmaceutical formulation as embodimented embodiments 1 to 32 for use in treating one or more autoimmune condition in a patient in need of such treatment comprising administering to the patient, at least one compound in an amount which is effective for the treatment.

39. A pharmaceutical formulation as embodimented in embodiment 38 wherein said autoimmune condition is selected from the group consisting of multiple sclerosis, systemic lupus erythematoses, myasthema gravis, rheumatoid arthritis, sjogrens disease, ulcerative colitis, and diabetes. 40. The pharmaceutical formulation as embodimented embodiments 1 to 32 for use in ameliorating immune damage and/or disease progression in a patient suffering from one or more autoimmune condition, comprising administering to the patient, at least one compound in an amount which is effective for the treatment. 41. The pharmaceutical formulation as embodimented embodiments 1 to 32 for use in treating cancer, comprising administering to the patient, at least one compound in an amount which is effective for the treatment.

42. The pharmaceutical formulation as embodimented in embodiment 40, wherein the cancer is selected from the group consisting of breast cancer, colon cancer, leukaemia, brain cancer, lung cancer, KS and melanoma.

43. The pharmaceutical formulation as embodimented embodiments 1 to 32 for use in reducing the possibility of onset of cancer in a patient in who is at risk for developing the cancer, comprising administering to the patient, at least one compound in an amount which is effective for the treatment. 44. The pharmaceutical formulation as embodimented embodiments 1 to 32 for use in reducing the possibility of transplanted organ rejection in a patient who has received an organ transplant, or a patient who is about to receive an organ transplant, comprising administering to the patient, at least one compound in an amount which is effective for the treatment. 45. The pharmaceutical formulation as embodimented embodiments 1 to 32 for use in treating asthma in a patient in need of such treatment, comprising administering to the patient, at least one compound in an amount which is effective for the treatment.

46. The pharmaceutical formulation as embodimented in embodiments 1 - 32 for use in treating wasting syndrome, comprising administering to said patient at least one compound in an amount which is effective for treatment.

47. The pharmaceutical formulation as embodimented in embodiments 1 - 32 for use in reducing the likelihood of wasting syndrome in a patient who is at risk of suffering wasting syndrome, comprising administering to said patient at least one compound in an amount which is effective for treatment. 48. The pharmaceutical formulation as embodimented in embodiments 1 - 32 for use in reducing the likelihood of cachexia in a patient who is about to undergo surgery, comprising administering to said patient, shortly before said surgery is performed, at least one compound in an amount which is effective for treatment.

49. The pharmaceutical formulation as embodimented in embodiments 1 - 32 for use in treating Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease in a patient in need of such treatment, comprising administering to said patient at least one compound in an amount which is effective for treatment. 50. The pharmaceutical formulation as embodimented in embodiments 1 - 32 for use in ameliorating immune damage and/or disease progression in a patient suffering from Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease comprising administering to said patient at least one compound in an amount which is effective for treatment.

51. A pharmaceutical formulation for use in ameliorating immune damage and/or disease progression in a patient suffering from Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease as embodimented in embodiment 45, wherein said patient is showing signs of wasting syndrome. 52. The pharmaceutical formulation as embodimented in embodiments 1 to 32 for use in treating conditions associated with elevated Tumour Necrosis Factor (TNF), Interleukin 1 or 2 and/or Interferon in a patient comprising administering to said patient at least one compound in an amount which is effective for treatment.

53. The pharmaceutical formulation as embodimented in embodiment 47 wherein said conditions may cause wasting syndrome.

54. The pharmaceutical formulation as embodimented in embodiments 1 to 32 for use in reducing the possibility of onset of conditions associated with elevated Tumour Necrosis Factor (TNF), Interleukin 1 or 2 and/or Interferon in a patient who is at risk for developing such conditions comprising administering to said patient at least one compound in an amount which is effective for treatment.

55. The pharmaceutical formulation as embodimented in embodiment 49 wherein the onset of said conditions may cause wasting syndrome.

56. The pharmaceutical formulation as embodimented in embodiments 1 to 32 for use in reducing the possibility of pre-term labour in a patient comprising administering to said patient at least one compound in an amount which is effective for treatment.

57. The pharmaceutical formulation as embodimented in embodiments 1 to 32 for use in treating Inflammatory bowel disease and/or respiratory distress syndrome in a patient in need of such treatment comprising administering to said patient at least one compound in an amount which is effective for treatment. 58. A pharmaceutical formulation comprising at least one compound, said compound comprising a peptide sequence which binds to antibody to clara cell protein.

59. The pharmaceutical formulation as embodimented in embodiment 53, wherein the compound consists of: a first residue consisting of the sequence which binds to antibody to clara cell protein; and at least one adjunct residue, the at least one adjunct residue being attached to the first residue.

60. The pharmaceutical formulation as embodimented in embodiment 54 wherein the adjunct residue consists of one to eighty amino acids. 61. The pharmaceutical formulation as embodimented in embodiments 54 or 55 wherein the adjunct residue consists of at least one positive charged amino acid.

62. The pharmaceutical formulation as embodimented in embodiments 54 to 56 wherein the adjunct residue consists of one to twenty amino acids of positive charge. 63. The pharmaceutical formulation as embodimented in embodiments 54 to 57 wherein the adjunct residue contains blocks of two or more adjacent amino acids of positive charge.

64. The pharmaceutical formulation as embodimented in embodiments 54 to 58 wherein the positive charged amino acid is either histidine, arginine and/or lysine. 65. The pharmaceutical formulation as embodimented in embodiment 54 to 59, wherein the adjunct residue is selected from the group consisting of (1) a peptide sequence residue comprising at least one amino acid residue, (2) a sugar residue, (3) a fatty acid residue and (4) a nucleotide sequence residue comprising at least one nucleotide residue. 66. The pharmaceutical formulation as embodimented in embodiment 60, wherein the sugar residue consists of heparin.

67. The pharmaceutical formulation as embodimented in embodiment 60, wherein the fatty acid residue is selected from the group consisting of C, to C₂₀ fatty acid.

68. The pharmaceutical formulation as embodimented in embodiment 62, wherein the fatty acid residue consists of diphosphatidyl choline.

69. The pharmaceutical formulation as embodimented in embodiments 54 to 63, wherein the adjunct residue is covalently bonded to the first residue at a C-terminal or an N-terminal end of the first residue.

70. The pharmaceutical formulation as embodimented in any one of embodiments 53 to 64, wherein the peptide sequence residue consists of albumin, lactoferrin, alpha fetoprotein, urinary protein, urinary protein 1 and or uteroglobin.

71. The pharmaceutical formulation as embodimented in any one of embodiments 53 to 65, wherein the compound is administered to the patient in plasma, the compound being present in the plasma in a concentration of from about 10 to about 5000 μg of the compound per mL of plasma.

72. The pharmaceutical formulation as embodimented in any one of embodiment 53 to 66, wherein the compound is administered to the patient in a dosage in the range of from about 10 μg to 20,000 μg per kilogram of body weight of the patient.

73. The pharmaceutical formulation as embodimented in any one of embodiments 53 to 67, wherein the patient is a neonate and the administering is effected prior to delivery of the neonate and/or during delivery of the neonate. 74. The pharmaceutical formulation as embodimented in any one of embodiments 53 to 68, wherein the peptide sequence is produced synthetically or is produced from a recombinant cell line.

75. The pharmaceutical formulation as embodimented in embodiment 69, wherein the recombinant cell line is a mammalian cell line, an insect cell line or a bacterial cell line.

76. The pharmaceutical formulation as embodimented in any one of embodiments 53 to 70, further comprising administering to the patient at least one antiviral compound and/or at least one immune altering compound. 77. A pharmaceutical formulation as embodimented in embodiment 70, wherein the anti-viral compound is a protease inhibitor and/or a reverse transcriptase inhibitor.

78. The pharmaceutical formulation as embodimented in any one of embodiments 53 - 72, wherein the patient is a human.

79. The pharmaceutical formulation as embodimented in any one of embodiments 53 to 73, wherein the patient is an animal.

80. The pharmaceutical formulation as embodimented in embodiments 53 to 74 wherein the compound is co-administered with Probenecid

81. The pharmaceutical formulation as embodimented in embodiments 53 to 75 wherein the compound is attached to a PEG molecule. 82. The pharmaceutical formulation as embodimented in embodiments 53 to 76 wherein at least two or more of the compounds are complexed together.

83. The pharmaceutical formulation as embodimented in embodiments 53 to

77, wherein the composition is administered enterically, parenterally, topically, orally, rectally, nasally or vaginally. 84. The pharmaceutical formulation as embodimented in embodiments 53 to

78, wherein the composition is administered intermittently.

85. The pharmaceutical formulation as embodimented in embodiments 53 to 79 wherein compound is administered in a therapeutic, sustained-release form.

86. A pharmaceutical formulation as embodimented in embodiments 53 to 80 further comprising administering an adjuvant to said patient.

87. The pharmaceutical formulation as embodimented in embodiments 53 to 81 for use in treating viral infection comprising administering to the patient at least one compound in an amount which is effective for the treatment.

88. The pharmaceutical formulation as embodimented in embodiment 82, wherein the virus is selected from the group consisting of HIV, Kaposi's Sarcoma- associated herpes virus, HHV-6, HHV-8, the viruses of the genus Molluscipoxvirus, HAV, HBV, HCV, and cytomegalovirus. 89. The pharmaceutical formulation for use in treating viral infection as embodimented in embodiment 82 or 83 wherein the virus is selected from the group consisting of togaviruses, flaviviruses, rubiviruses, pestiviruses and hantaviruses.

90. The pharmaceutical formulation as embodimented embodiments 53 to 81 for use in reducing the likelihood of viral infection in a patient who is at risk for suffering viral infection comprising administering to the patient at least one compound in an amount which is effective for the treatment.

91. The pharmaceutical formulation as embodimented embodiments 53 to 81 for use in reducing the likelihood of septic shock syndrome in a patient who is about to undergo surgery comprising administering to the patient, shortly before the surgery is performed, at least one compound in an amount which is effective for the treatment.

92. The pharmaceutical formulation as embodimented embodiments 53 to 81 for use in treating septic shock syndrome in a patient who has recently undergone surgery comprising administering to the patient, at least one compound in an amount which is effective for the treatment.

93. The pharmaceutical formulation as embodimented embodiments 53 to 81 for use in treating one or more autoimmune condition in a patient in need of such treatment comprising administering to the patient, at least one compound in an amount which is effective for the treatment. 94. A pharmaceutical formulation as embodimented in embodiment 88 wherein said autoimmune condition is selected from the group consisting of multiple sclerosis, systemic lupus erythematoses, myasthema gravis, rheumatoid arthritis, sjogrens disease, ulcerative colitis, and diabetes.

95. The pharmaceutical formulation as embodimented embodiments 53 to 81 for use in ameliorating immune damage and/or disease progression in a patient suffering from one or more autoimmune condition, comprising administering to the patient, at least one compound in an amount which is effective for the treatment.

96. The pharmaceutical formulation as embodimented embodiments 53 to 81 for use in treating cancer, comprising administering to the patient, at least one compound in an amount which is effective for the treatment.

97. The pharmaceutical formulation as embodimented in embodiment 90, wherein the cancer is selected from the group consisting of breast cancer, colon cancer, leukaemia, brain cancer, lung cancer, KS and melanoma.

98. The pharmaceutical formulation as embodimented embodiments 53 to 81 for use in reducing the possibility of onset of cancer in a patient in who is at risk for developing the cancer, comprising administering to the patient, at least one compound in an amount which is effective for the treatment. 99. The pharmaceutical formulation as embodimented embodiments 53 to 81 for use in reducing the possibility of transplanted organ rejection in a patient who has received an organ transplant, or a patient who is about to receive an organ transplant, comprising administering to the patient, at least one compound in an amount which is effective for the treatment.

100. The pharmaceutical formulation as embodimented in embodiments 53 to 81 for use in treating asthma in a patient in need of such treatment, comprising administering to the patient, at least one compound in an amount which is effective for the treatment.

101. The pharmaceutical formulation as embodimented in embodiments 53 to 81 for use in treating wasting syndrome in a patient in need of such treatment, comprising administering to said patient at least one compound in an amount which is effective for treatment.

102. The pharmaceutical formulation as embodimented in embodiments 53 to 81 for use in treating wasting syndrome, comprising administering to said patient at least one compound in an amount which is effective for treatment.

103. The pharmaceutical formulation as embodimented in embodiments 53 to 81 for use in reducing the likelihood of wasting syndrome in a patient who is at risk of suffering wasting syndrome, comprising administering to said patient at least one compound in an amount which is effective for treatment. 104. The pharmaceutical formulation as embodimented in embodiments 53 to 81 for use in reducing the likelihood of cachexia in a patient who is about to undergo surgery, comprising administering to said patient, shortly before said surgery is performed, at least one compound in an amount which is effective for treatment.

105. The pharmaceutical formulation as embodimented in embodiments 53 to 81 for use in treating Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease in a patient in need of such treatment, comprising administering to said patient at least one compound in an amount which is effective for treatment.

106. The pharmaceutical formulation as embodimented in embodiments 53 to 81 for use in ameliorating immune damage and/or disease progression in a patient suffering from Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease comprising administering to said patient at least one compound in an amount which is effective for treatment.

107. A pharmaceutical formulation for use in ameliorating immune damage and/or disease progression in a patient suffering from Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease as embodimented in embodiment 95, wherein said patient is showing signs of wasting syndrome. 108. The pharmaceutical formulation as embodimented in embodiments 53 to 81 for use in treating conditions associated with elevated Tumour Necrosis Factor (TNF), Interleukin 1 or 2 and/or Interferon in a patient comprising administering to said patient at least one compound in an amount which is effective for treatment. 109. The pharmaceutical formulation as embodimented in embodiment 97 wherein said conditions may cause wasting syndrome.

110. The pharmaceutical formulation as embodimented in embodiments 53 to 81 for use in reducing the possibility of onset of conditions associated with elevated Tumour Necrosis Factor (TNF), Interleukin 1 or 2 and/or Interferon in a patient who is at risk for developing such conditions comprising administering to said patient at least one compound in an amount which is effective for treatment.

111. The pharmaceutical formulation as embodimented in embodiment 99 wherein the onset of said conditions may cause wasting syndrome.

112. The pharmaceutical formulation as embodimented in embodiments 53 to 81 for use in reducing the possibility of pre-term labour in a patient comprising administering to said patient at least one compound in an amount which is effective for treatment.

113. The pharmaceutical formulation as embodimented in embodiments 53 to 81 for use in treating Inflammatory bowel disease and/or respiratory distress syndrome in a patient in need of such treatment comprising administering to said patient at least one compound in an amount which is effective for treatment.

114. A pharmaceutical formulation comprising a pharmaceutically acceptable carrier and at least one compound, said compound comprising a peptide sequence selected from the group consisting of: SEQ ID NO. 1 to SEQ ID NO. 118, conservative variants of SEQ ID NO. 1 to SEQ ID NO. 118, SEQ ID NO. 122 to SEQ ID NO. 134, and conservative variants of SEQ ID NO. 122 to SEQ ID NO. 134, any of which bind to antibody to clara cell protein and a pharmaceutically acceptable carrier.

115. The pharmaceutical formulation as embodimented in embodiment 114, wherein said compound consists of any one of: a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a part of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, the part of a sequence having at least four amino acid residues; a conservative variant of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a conservative variant of a portion of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, the portion of a sequence having at least four amino acid residues; a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; a part of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 , the part of a sequence having at least four amino acid residues; a conservative variant of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 or a conservative variant of a portion of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 , the portion of a sequence having at least four amino acid residues, any of which binds to antibody to clara cell protein. 116. The pharmaceutical formulation as embodimented in embodiment 114, wherein said compound consists of at least one of: a first residue consisting of: a residue of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a conservative variant of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a conservative variant of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; a residue of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; a residue of a conservative variant of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 or a residue of a conservative variant of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; which binds to antibody to clara cell protein; and at least one adjunct residue, said adjunct residue being attached to the first residue.

117. The pharmaceutical formulation as embodimented in embodiment 116 wherein the adjunct residue consists of one to eighty amino acids.

118. The pharmaceutical formulation as embodimented in embodiments 116 or

117 wherein the adjunct residue consists of at least one positive charged amino acid. 119. The pharmaceutical formulation as embodimented in embodiments 116 to

118 wherein the adjunct residue consists of one to twenty amino acids of positive charge.

120. The pharmaceutical formulation as embodimented in embodiments 116 to

119 wherein the adjunct residue contains blocks of two or more adjacent amino acids of positive charge. 121. The pharmaceutical formulation as embodimented in embodiments 118 - 120 wherein the positive charged amino acid is either histidine, arginine and/or lysine.

122. The pharmaceutical formulation as embodimented in embodiment 116 to 121 , wherein the adjunct residue is selected from the group consisting of (1) a peptide sequence residue comprising at least one amino acid residue, (2) a sugar residue, (3) a fatty acid residue and (4) a nucleotide sequence residue comprising at least one nucleotide residue.

123. The pharmaceutical formulation as embodimented in embodiment 122, wherein the sugar residue consists of heparin.

124. The pharmaceutical formulation as embodimented in embodiment 122, wherein the fatty acid residue is selected from the group consisting of C_η to C₂₀ fatty acid.

125. The pharmaceutical formulation as embodimented in embodiment 124, wherein the fatty acid residue consists of diphosphatidyl choline.

126. The pharmaceutical formulation as embodimented in embodiments 114 to 125, wherein the adjunct residue is covalently bonded to the first residue at a C-terminal or an N-terminal end of the first residue.

127. The pharmaceutical formulation as embodimented in any one of embodiments 114 to 126, wherein the peptide sequence residue consists of albumin, lactoferrin, alpha fetoprotein, urinary protein, urinary protein 1 and or uteroglobin.

128. The pharmaceutical formulation as embodimented in any one of embodiments 114 to 127, wherein the compound is administered to the patient in plasma, the compound being present in the plasma in a concentration of from about 10 to about 5000 μg of the compound per mL of plasma.

129. The pharmaceutical formulation as embodimented in any one of embodiments 114 to 128, wherein the compound is administered to the patient in a dosage in the range of from about 10 μg to 20,000 μg per kilogram of body weight of the patient. 130. The pharmaceutical formulation as embodimented in any one of embodiments 114 to 129, wherein the patient is a neonate and the administering is effected prior to delivery of the neonate and/or during delivery of the neonate.

131. The pharmaceutical formulation as embodimented in any one of embodiments 114 to 130, wherein the peptide sequence is produced synthetically or is produced from a recombinant cell line.

132. The pharmaceutical formulation as embodimented in embodiment 131 , wherein the recombinant cell line is a mammalian cell line, an insect cell line or a bacterial cell line.

133. The pharmaceutical formulation as embodimented in any one of embodiments 114 to 132, further comprising administering to the patient at least one antiviral compound and/or at least one immune altering compound.

134. A pharmaceutical formulation as embodimented in embodiment 133, wherein the anti-viral compound is a protease inhibitor and/or a reverse transcriptase inhibitor. 135. The pharmaceutical formulation as embodimented in any one of embodiments 114 to 134, wherein the patient is a human. 136. The pharmaceutical formulation as embodimented in any one of embodiments 114 to 135, wherein the patient is an animal.

137. The pharmaceutical formulation as embodimented in any one of embodiments 114 to 136 wherein the compound is co-administered with probenecid. 138. The pharmaceutical formulation as embodimented in any one of embodiments 114 to 137 wherein the compound is attached to a PEG molecule.

139. The pharmaceutical formulation as embodimented in any one of embodiments 103 to 127 wherein at least two or more of the compounds are complexed together. 140. The pharmaceutical formulation as embodimented in embodiments 114 to

139, wherein the composition is administered enterically, parenterally, topically, orally, rectally, nasally or vaginally.

141. The pharmaceutical formulation as embodimented in embodiments 114 to

140, wherein the composition is administered intermittently. 142. The pharmaceutical formulation as embodimented in embodiments 114 to

141 wherein compound is administered in a therapeutic, sustained-release form.

143. A pharmaceutical formulation as embodimented in embodiments 114 to 142 further comprising an adjuvant.

144. The pharmaceutical formulation as embodimented in embodiments 114 to 143 for use in treating a viral infection said use comprising administering to the patient at least one compound in an amount which is effective for the treatment.

145. The pharmaceutical formulation as embodimented in embodiment 144, wherein the virus is selected from the group consisting of HIV, Kaposi's Sarcoma- associated herpes virus, HHV-6, HHV-8, the viruses of the genus Molluscipoxvirus, HAV, HBV, HCV and cytomegalovirus.

146. The pharmaceutical formulation for use in treating viral infection as embodimented in embodiment 144 wherein the virus is selected from the group consisting of togaviruses, flaviviruses, rubiviruses, pestiviruses and hantavirus.

147. The pharmaceutical formulation as embodimented embodiments 114 to 142 for use in reducing the likelihood of viral infection in a patient who is at risk for suffering viral infection comprising administering to the patient at least one compound in an amount which is effective for the treatment.

148. The pharmaceutical formulation as embodimented embodiments 114 to 142 for use in reducing the likelihood of septic shock syndrome in a patient who is about to undergo surgery comprising administering to the patient, shortly before the surgery is performed, at least one compound in an amount which is effective for the treatment. 149. The pharmaceutical formulation as embodimented embodiments 114 to 142 for use in treating septic shock syndrome in a patient who has recently undergone surgery comprising administering to the patient, at least one compound in an amount which is effective for the treatment. 150. The pharmaceutical formulation as embodimented embodiments 114 to 142 for use in treating one or more autoimmune condition in a patient in need of such treatment comprising administering to the patient, at least one compound in an amount which is effective for the treatment.

151. A pharmaceutical formulation as embodimented in embodiment 150 wherein said autoimmune condition is selected from the group consisting of multiple sclerosis, systemic lupus erythematoses, myasthema gravis, rheumatoid arthritis, sjogrens disease, ulcerative colitis, and diabetes.

152. The pharmaceutical formulation as embodimented embodiments 114 to 142 for use in ameliorating immune damage and/or disease progression in a patient suffering from one or more autoimmune condition, comprising administering to the patient, at least one compound in an amount which is effective for the treatment.

153. The pharmaceutical formulation as embodimented embodiments 114 to 142 for use in treating cancer, comprising administering to the patient, at least one compound in an amount which is effective for the treatment. 154. The pharmaceutical formulation as embodimented in embodiment 153, wherein the cancer is selected from the group consisting of breast cancer, colon cancer, leukaemia, brain cancer, lung cancer, KS and melanoma.

155. The pharmaceutical formulation as embodimented in embodiments 114 to 142 for use in reducing the possibility of onset of cancer in a patient in who is at risk for developing the cancer, comprising administering to the patient, at least one compound in an amount which is effective for the treatment.

156. The pharmaceutical formulation as embodimented embodiments 114 to 142 for use in reducing the possibility of transplanted organ rejection in a patient who has received an organ transplant, or a patient who is about to receive an organ transplant, comprising administering to the patient, at least one compound in an amount which is effective for the treatment.

157. The pharmaceutical formulation as embodimented embodiments 114 to 142 for use in treating asthma in a patient in need of such treatment, comprising administering to the patient, at least one compound in an amount which is effective for the treatment. 158. The pharmaceutical formulation as embodimented in embodiments 114 to

142 for use in treating wasting syndrome, comprising administering to said patient at least one compound in an amount which is effective for treatment. 159. The pharmaceutical formulation as embodimented in embodiments 114 to 142 for use in reducing the likelihood of wasting syndrome in a patient who is at risk of suffering wasting syndrome, comprising administering to said patient at least one compound in an amount which is effective for treatment. 160. The pharmaceutical formulation as embodimented in embodiments 114 to

142 for use in reducing the likelihood of cachexia in a patient who is about to undergo surgery, comprising administering to said patient, shortly before said surgery is performed, at least one compound in an amount which is effective for treatment.

161. The pharmaceutical formulation as embodimented in embodiments 114 to 142 for use in treating Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease in a patient in need of such treatment, comprising administering to said patient at least one compound in an amount which is effective for treatment.

162. The pharmaceutical formulation as embodimented in embodiments 114 to 142 for use in ameliorating immune damage and/or disease progression in a patient suffering from Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease comprising administering to said patient at least one compound in an amount which is effective for treatment.

163. A pharmaceutical formulation for use in ameliorating immune damage and/or disease progression in a patient suffering from Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease as embodimented in embodiment 162, wherein said patient is showing signs of wasting syndrome.

164. The pharmaceutical formulation as embodimented in embodiments 114 to 142 for use in treating conditions associated with elevated Tumour Necrosis Factor (TNF), Interleukin 1 or 2 and/or Interferon in a patient comprising administering to said patient at least one compound in an amount which is effective for treatment.

165. The pharmaceutical formulation as embodimented in embodiment 164 wherein said conditions may cause wasting syndrome.

166. The pharmaceutical formulation as embodimented in embodiments 114 to 142 for use in reducing the possibility of onset of conditions associated with elevated Tumour Necrosis Factor (TNF), Interleukin 1 or 2 and/or Interferon in a patient who is at risk for developing such conditions comprising administering to said patient at least one compound in an amount which is effective for treatment.

167. The pharmaceutical formulation as embodimented in embodiment 166 wherein the onset of said conditions may cause wasting syndrome. 168. The pharmaceutical formulation as embodimented in embodiments 114 to

142 for use in reducing the possibility of pre-term labour in a patient comprising administering to said patient at least one compound in an amount which is effective for treatment.

169. The pharmaceutical formulation as embodimented in embodiments 114 to 142 for use in treating Inflammatory bowel disease and/or respiratory distress syndrome in a patient in need of such treatment comprising administering to said patient at least one compound in an amount which is effective for treatment.

170. A pharmaceutical formulation for use in prophylaxis against viral infections comprising administering to the patient His-His-His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe- Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

171. A pharmaceutical formulation for use in treatment of patients infected with a virus comprising administering to the patient His-His-His-His-His-His-Glu-lle-Cys-Pro-Ser- Phe-Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

172. A pharmaceutical formulation for use in reduction of the likelihood of viral infection in a patient who is at risk from suffering from a viral infection comprising administering to the patient His-His-His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe-Gln-Arg-Val- lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

173. A pharmaceutical formulation for use in reduction of the likelihood of septic shock caused by surgery comprising administering to the patient His-His-His-His-His-His- Glu-lle-Cys-Pro-Ser-Phe-Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr- Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

174. A pharmaceutical formulation for use in reduction of the likelihood of septic shock syndrome in a patient who is about to undergo surgery, comprising administering to the patient, prior to surgery, His-His-His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe-Gln-Arg-Val- lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

175. A pharmaceutical formulation for use in treatment of septic shock, comprising administering to the patient His-His-His-His-His-His-Glu-Ile-Cys-Pro-Ser-Phe- Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent. 176. A pharmaceutical formulation for use in treatment of autoimmune conditions, comprising administering to the patient His-His-His-His-His-His-Glu-lle-Cys- Pro-Ser-Phe-Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

177. A pharmaceutical formulation for use in amelioration of immune damage and/or disease progression in a patient suffering from one or more autoimmune condition, comprising administering to the patient His-His-His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe- Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment.

178. A pharmaceutical formulation for use in treatment of different types of cancer, comprising administering to the patient His-His-His-His-His-His-Glu-lle-Cys-Pro- Ser-Phe-Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

179. A pharmaceutical formulation for use in prophylaxis against cancer, comprising administering to the patient His-His-His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe- Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Aia in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

180. A pharmaceutical formulation for use in reduction of the possibility of transplanted organ rejection, comprising administering to the patient His-His-His-His-His- His-Glu-lle-Cys-Pro-Ser-Phe-Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser- Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

181. A pharmaceutical formulation for use in treatment of asthma, comprising administering to the patient His-His-His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe-Gln-Arg-Val- lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

182. A pharmaceutical formulation for use in treatment of different types of cancer, comprising administering to the patient His-His-His-His-His-His-Glu-lle-Cys-Pro- Ser-Phe-Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

183. A pharmaceutical formulation for use in treatment of a person whose immune system has been compromised, comprising administering to the patient His-His- His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe-Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr- Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

184. A pharmaceutical formulation for use in treatment of wasting syndrome, comprising administering to the patient His-His-His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe- Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

185. A pharmaceutical formulation for use in reducing the likelihood of wasting syndrome, comprising administering to the patient His-His-His-His-His-His-Glu-lle-Cys- Pro-Ser-Phe-Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

186. A pharmaceutical formulation for use in treating cachexia, comprising administering to the patient His-His-His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe-Gln-Arg-Val- lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

187. A pharmaceutical formulation for use in reducing the likelihood of cachexia, comprising administering to the patient His-His-His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe- Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

188. A pharmaceutical formulation for use in treating Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease, comprising administering to the patient His-His- His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe-Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr- Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

189. A pharmaceutical formulation for use in ameliorating immune damage and/or disease progression in a patient suffering from Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease, comprising administering to the patient His-His-His-His- His-His-Glu-lle-Cys-Pro-Ser-Phe-Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser- Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

190. A pharmaceutical formulation for use in treating conditions associated with elevated Tumour Necrosis Factor (TNF), Interleukin 1 or 2 and/or Interferon, comprising administering to the patient His-His-His-His-His-His-Glu-Ile-Cys-Pro-Ser-Phe-Gln-Arg-Val- lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

191. A pharmaceutical formulation for use in reducing the possibility of pretoterm labour, comprising administering to the patient His-His-His-His-His-His-Glu-lle-Cys-Pro- Ser-Phe-Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent. 192. A pharmaceutical formulation for use treating inflammatory bowel disease comprising administering to the patient His-His-His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe- Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent. 193. A pharmaceutical formulation for use in respiratory distress syndrome comprising administering to the patient His-His-His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe- Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala in an amount which is effective for the treatment; in a pharmaceutically acceptable carrier or diluent.

194. A composition or pharmaceutical formulation, comprising incorporating DNA in a patient's cells such that these cells can produce endogenous levels of at least one compound, said compound comprising a peptide sequence selected from the group consisting of:

-SEQ ID NO. 1 to SEQ ID NO. 118; conservative variants of SEQ ID NO. 1 to SEQ ID NO. 118; SEQ ID NO. 122 to SEQ ID NO. 134; conservative variants of SEQ ID NO. 122 to SEQ ID NO. 134.

195. A composition or pharmaceutical as embodimented in embodiment 194, wherein said at least one compound consists of: a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a part of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, the part of a sequence having at least four amino acid residues; a conservative variant of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a conservative variant of a portion of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, the portion of a sequence having at least four amino acid residues; a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; a part of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 , the part of a sequence having at least four amino acid residues; a conservative variant of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 or a conservative variant of a portion of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134, the portion of a sequence having at least four amino acid residues.

196. A composition or pharmaceutical formulation as embodimented in embodiment 194 wherein said at least one compound consists of: compound consists of: a first residue consisting of: a residue of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a conservative variant of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a conservative variant of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134;

-a residue of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; a residue of a conservative variant of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 or a residue of a conservative variant of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; and at least one adjunct residue, the at least one adjunct residue being attached to the first residue. 197. A composition or pharmaceutical formulation as embodimented in any one of embodiments 194 to 196 wherein said DNA consists of or comprises SEQ ID NO:119 or SEQ ID NO:120 or SEQ ID NO:121 or any of the sequences SEQ ID NO: 135 to SEQ ID NO: 147.

198. A composition or pharmaceutical formulation as embodimented in any one of embodiments 194 to 197 wherein said compound comprises SEQ ID NO: 132.

199. A composition or pharmaceutical formulation as embodimented in any one of embodiments 194 to 198, wherein the DNA coding the Clara Cell Protein is injected into the patient's cells in situ using a vaccination, and without steps of in-vitro alteration or culture of the patients cells, whereby such steps are not required. 200. The composition or pharmaceutical formulation as embodimented in embodiments 194 to 199 for use in treating viral infection comprising administering to the patient at least one compound in an amount which is effective for the treatment.

201. The composition or pharmaceutical formulation as embodimented in embodiment 200, wherein the virus is selected from the group consisting of HIV, Kaposi's Sarcoma-associated herpes virus, the viruses of the genus Molluscipoxvirus, the viruses of the genus hepatitis, and the virus cytomegalovirus.

202. The composition or pharmaceutical formulation for use in treating viral infection as embodimented in embodiment 200 or 201 wherein the virus is selected from the group consisting of togaviruses, flaviviruses, rubiviruses, pestiviruses and hantavirus. 203. The composition or pharmaceutical formulation as embodimented embodiments 194 to 199 for use in reducing the likelihood of viral infection in a patient who is at risk for suffering viral infection comprising administering to the patient at least one compound in an amount which is effective for the treatment.

204. The composition or pharmaceutical formulation as embodimented embodiments 194 to 200 for use in reducing the likelihood of septic shock syndrome in a patient who is about to undergo surgery comprising administering to the patient, shortly before the surgery is performed, at least one compound in an amount which is effective for the treatment.

205. The composition or pharmaceutical formulation as embodimented embodiments 194 to 200 for use in treating septic shock syndrome in a patient who has recently undergone surgery comprising administering to the patient, at least one compound in an amount which is effective for the treatment.

206. The composition or pharmaceutical formulation as embodimented embodiments 194 to 199 for use in treating one or more autoimmune condition in a patient in need of such treatment comprising administering to the patient, at least one compound in an amount which is effective for the treatment.

207. A composition or pharmaceutical formulation as embodimented in embodiment 195 wherein said autoimmune condition is selected from the group consisting of multiple sclerosis, systemic lupus erythematoses, myasthema gravis, rheumatoid arthritis, sjogrens disease, ulcerative colitis, and diabetes. 208. The composition or pharmaceutical formulation as embodimented embodiments 193 to 198 for use in ameliorating immune damage and/or disease progression in a patient suffering from one or more autoimmune condition, comprising administering to the patient, at least one compound in an amount which is effective for the treatment. 209. The composition or pharmaceutical formulation as embodimented embodiments 193 to 198 for use in treating cancer, comprising administering to the patient, at least one compound in an amount which is effective for the treatment.

210. The pharmaceutical formulation as embodimented in embodiment 208, wherein the cancer is selected from the group consisting of breast cancer, colon cancer, leukemia, brain cancer, lung cancer.

211. The pharmaceutical formulation as embodimented embodiments 194 to 199 for use in reducing the possibility of onset of cancer in a patient in who is at risk for developing the cancer, comprising administering to the patient, at least one compound in an amount which is effective for the treatment. 212. The pharmaceutical formulation as embodimented embodiments 194 to 199 for use in reducing the possibility of transplanted organ rejection in a patient who has received an organ transplant, or a patient who is about to receive an organ transplant, comprising administering to the patient, at least one compound in an amount which is effective for the treatment. 213. The pharmaceutical formulation as embodimented embodiments 194 to 199 for use in treating asthma in a patient in need of such treatment, comprising administering to the patient, at least one compound in an amount which is effective for the treatment. 214. The pharmaceutical formulation as embodimented in embodiments 193 to

198 for use in treating wasting syndrome, comprising administering to said patient at least one compound in an amount which is effective for treatment.

215. The pharmaceutical formulation as embodimented in embodiments 193 to 198 for use in reducing the likelihood of wasting syndrome in a patient who is at risk of suffering wasting syndrome, comprising administering to said patient at least one compound in an amount which is effective for treatment.

216. The pharmaceutical formulation as embodimented in embodiments 194 to

199 for use in reducing the likelihood of cachexia in a patient who is about to undergo surgery, comprising administering to said patient, shortly before said surgery is performed, at least one compound in an amount which is effective for treatment.

217. The pharmaceutical formulation as embodimented in embodiments 194 to 199 for use in treating Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease in a patient in need of such treatment, comprising administering to said patient at least one compound in an amount which is effective for treatment.

218. The pharmaceutical formulation as embodimented in embodiments 194 to 199 for use in ameliorating immune damage and/or disease progression in a patient suffering from Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease comprising administering to said patient at least one compound in an amount which is effective for treatment.

219. A pharmaceutical formulation for use in ameliorating immune damage and/or disease progression in a patient suffering from Motor Neuron disease, Multiple Sclerosis and/or Crohn's disease as embodimented in embodiment 218, wherein said patient is showing signs of wasting syndrome. 220. The pharmaceutical formulation as embodimented in embodiments 194 to

199 for use in treating conditions associated with elevated Tumour Necrosis Factor (TNF), Interleukin 1 or 2 and/or Interferon in a patient comprising administering to said patient at least one compound in an amount which is effective for treatment.

221. The pharmaceutical formulation as embodimented in embodiment 220 wherein said conditions may cause wasting syndrome.

222. The pharmaceutical formulation as embodimented in embodiments 194 to 199 for use in reducing the possibility of onset of conditions associated with elevated Tumour Necrosis Factor (TNF), Interleukin 1 or 2 and/or Interferon in a patient who is at risk for developing such conditions comprising administering to said patient at least one compound in an amount which is effective for treatment.

223. The pharmaceutical formulation as embodimented in embodiment 222 wherein the onset of said conditions may cause wasting syndrome. 224. The pharmaceutical formulation as embodimented in embodiments 194 to 199 for use in reducing the possibility of pre-term labour in a patient comprising administering to said patient at least one compound in an amount which is effective for treatment. 225. The pharmaceutical formulation as embodimented in embodiments 194 to

199 for use in treating Inflammatory bowel disease and/or respiratory distress syndrome in a patient in need of such treatment comprising comprising administering to said patient at least one compound in an amount which is effective for treatment.

226. A pharmaceutical formulation for use in establishing a pro-hematopoietic activity in a patient comprising administering to the patient at least one compound in an amount which is effective for the activity, the compound comprising a peptide sequence selected from the group consisting of: SEQ ID NO. 1 to SEQ ID NO. 118; conservative variants of SEQ ID NO. 1 to SEQ ID NO. 118; SEQ ID NO. 122 to SEQ ID NO. 134; conservative variants of SEQ ID NO. 122 to SEQ ID NO. 134. 227. A pharmaceutical formulation for use in establishing a pro-hematopoietic activity as embodimented in embodiment 226, wherein the compound consists of at least one of: a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a part of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, said part of a sequence having at least four amino acid residues; a conservative variant of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a conservative variant of a portion of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, said portion of a sequence having at least four amino acid residues; a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; a part of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 , said part of a sequence having at least four amino acid residues; a conservative variant of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 or a conservative variant of a portion of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 , said portion of a sequence having at least four amino acid residues. 228. A pharmaceutical formulation for use in establishing a pro-hematopoietic activity as embodimented in embodiment 226, wherein the at least one compound consists of: a first residue consisting of at least one of: a residue of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a conservative variant of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a conservative variant of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; a residue of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; a residue of a conservative variant of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 or a residue of a conservative variant of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; and at least one adjunct residue, the at least one adjunct residue being attached to the first residue. 229. The pharmaceutical formulation as embodimented in embodiment 228 wherein the adjunct residue consists of one to eighty amino acids.

230. The pharmaceutical formulation as embodimented in embodiments 228 or 229 wherein the adjunct residue consists of positive charged amino acids.

231. The pharmaceutical formulation as embodimented in embodiments 228 to 229 wherein the adjunct residue consists of one to twenty amino acids of positive charge.

232. The pharmaceutical formulation as embodimented in embodiments 228 to 231 wherein the adjunct residue contains blocks of two or more adjacent amino acids of positive charge.

233. The pharmaceutical formulation as embodimented in embodiments 228 to 232 wherein the positive charged amino acid is either histidine, arginine and/or lysine.

234. The pharmaceutical formulation as embodimented in embodiment 228 to 233, wherein the adjunct residue is selected from the group consisting of (1) a peptide sequence residue comprising at least one amino acid residue, (2) a sugar residue, (3) a fatty acid residue and (4) a nucleotide sequence residue comprising at least one nucleotide residue.

235. The pharmaceutical formulation as embodimented in embodiment 234, wherein the sugar residue consists of heparin.

236. The pharmaceutical formulation as embodimented in embodiment 235, wherein the fatty acid residue is selected from the group consisting of C_η to C₂₀ fatty acid. 237. The pharmaceutical formulation as embodimented in embodiment 236, wherein the fatty acid residue is diphosphatidyl choline.

238. The pharmaceutical formulation as embodimented in embodiments 228 to

237, wherein the adjunct residue is covalently bonded to the first residue at a C-terminal or an N-terminal end of the first residue. 239. The pharmaceutical formulation as embodimented in any one of embodiments 226 to 238, wherein the peptide sequence residue consists of albumin, lactoferrin, alpha fetoprotein, urinary protein, urinary protein 1 and or uteroglobin. 240. A pharmaceutical formulation suitable for administration to a patient, the formulation comprising Clara Cells and a cage or solid support.

241. A pharmaceutical formulation as embodimented in embodiment 240, wherein said cage or solid support comprises one or more of microporous Nylon ™, collagen and hyaluronic acid.

EXAMPLES These and other features and advantages of the present invention will be more clearly understood with reference to the following description of some embodiments thereof and with reference to the accompanying tables and figures described below.

Purification and characterization of P1. Clara cell protein, with sequence identical to P1 was isolated from 20 litres of pooled urines from six pregnant patients at third trimester stage. Purification of P1 was carried out using the Pharmacia FPLC system consisting of an automated injector ACT 100, a gradient programmer GP-250 Plus, two P- 500 pumps and a Dual Path Monitor UV-2 (274 and 254 nm) with 1 and 20 mm flow cells (Pharmacia-LKB Biotechnology S-75182, Uppsala, Sweden). All columns (Sephacryl S- 200 C26/100, Hiload 26/10 Q Sepharose and mono P HR 5/5) were from Pharmacia-LKB Biotechnology. The principal contaminant to eliminate during purification was retinol binding protein (RBP), an 18.4-kDa -microprotein about 20 times more concentrated than P1 in the starting urine. A complete separation was achieved by the following procedure in which the two proteins were traced by a sensitive latex immunoassay using the antibodies from Dako (Glostrup, Denmark). After a 200-fold concentration by pressure ultrafiltration on Amicon. PM 10 (W.R. Grace & Co, Amicon Division, Danvers, MA 01923, USA), urinary proteins were fractionated on Sephacryl S-200 in 0.05 M Tris-HCI buffer, pH 7.4, containing 0.2 M NaCI. Fractions containing P1 were localized with the latex immunoassay at an apparent M₅ of about 20 kDa. After dialysis against 0.01 M Tris-HCI buffer, pH 8, they were chromatographed on a Hiload 26/10 Q Sepharose column with a 0.1-0.3 M NaCI gradient in 0.01 M Tris-HCI. buffer, pH 8. Fractions containing immunoreactive P1 were then refractionated on Sephacryl S-200 as described above. After dialysis against 0.02 M N-methylpiperazine, pH 4.7, the P1 peak was subjected to a final purification by chromatofocusing on a mono P HR 5/5 column with 50 ml of Polybuffer 74 diluted 10- times and adjusted to pH 4. Two major fractions absorbing at 280 nm were desorbed, one at a pH of 4.5 containing P1 and a second one at a pH of 4.3 formed by a protein which was not identified. Purified Clara cell protein was analyzed by electrophoresis on polyacrylamide gel

(7.5%) in a 0.1-M phosphate buffer, pH 7.1 , containing 0.1% of SDS. Reduction was performed with 1% of 2-mercaptoethanol. Electrophoresis was carried out with the LKB 2117 Multiphor according to the instructions of the manufacturer (Pharmacia-LKB, Sweden). The bands were stained with Coomassie Brilliant Blue. Ouchtorlony immunodiffission analysis was performed in 1% agarose gel in 0.1 M phosphate buffer, pH 7.4, containing 0. 15 M NaCI. After 24 h diffusion, the gel was washed (0. 15 M NaCI), dried and stained with Coomassie Brilliant Blue. Clara cell protein was pyridyl ethylated by the method of Friedman et al. and the NH2-terminal amino acid sequencing was performed using the Applied Biosystems 477A/20A sequencing system (Applied Biosystems, Foster City, CA, USA).

P1 Purification and amino acid sequence. Six milligrams of Clara cell protein or (P1) were recovered from 20 litres of urine (overall yield of 15%). The purified fraction contained <0.1% of RBP (measured by latex immunoassay). In SDS-PAGE, unreduced Clara cell protein appeared as a single band.

The amino acid sequencing of the intact protein confirmed its high degree of purity since a single signal was obtained at each cycle. The following partial amino acid sequence was obtained: Glu-lle-Cys-Pro-Ser-Phe-Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met- Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala (SEQ ID NO:1). These 24 amino acids showed complete identity with those of human CC10 after comparison in the EMBL data bank using the FASTA program. (Pearson W.R. Lipman D.J. - Improved Tools for Biological Sequence Comparison. Aroc Nath Acad Sci U.S.A. 1988;85:2444-2549). Furthermore, sequences and compounds of the present invention can be obtained by other isolation techniques (e.g., to isolate Clara cell protein from body fluid-e.g. amniotic fluid, sputum, urine, semen, blood, and/or by synthetic production). Also, sequences and compounds of the present invention can be produced from recombinant cell lines, e.g., using any cell lines known in the art, such as the cell line "RL-65", disclosed in U.S. Patent No. 5,830,685, the entirety of which is incorporated herein by reference. In addition, other cell lines are known to those skilled in the art, and it is very likely that others will become known to the art, and any of these can be used to obtain compounds and/or sequences used in the methods of the present invention and/or in the articles of the present invention. Furthermore, those of skill in the art would readily be able to select suitable cells into which genes can be inserted such that the cell produces peptides and/or other compounds used in the methods of the present invention and/or in the articles of the present invention.

Respiratory Tract Secretions. The identity between P1 and CC10 was corroborated by the observation of high concentrations of P1 in respiratory tract secretions. P1 is particularly abundant in sputum with a mean concentration around 50 mg/L in healthy subjects. P1 in sputum undoubtedly originates from the respiratory airways since the protein is hardly detectable in saliva. Average concentrations in BAL fluids are about 10 times lower than in sputum. P1 is slightly more concentrated in bronchial, than in alveolar lavages, which agrees with its localization in respiratory bronchioles. P1 represented on average 7.2 + 4.2 (S.D., n = 16) % of the total protein content of BAL fluids. The concentration of P1 in lung parenchyma measured in the homogenate of a fresh tissue was 6 μg/g wet weight.

Urogenital Secretions. P1 and CC10 are both present in relatively high concentrations in several urogenital secretions from healthy subjects. P1 is excreted in urine in amounts, which are greater in males than in females. This sex difference appears and becomes maximal at puberty. In the age group 10-15 years, the median value of urinary P1 is about two orders of magnitude higher in boys than in girls. We could establish the existence of a post renal source for P1 in man by monitoring the concentration of the protein during micturition. The concentration of P1 is very high in the first millilitres of urine emitted and then declines markedly, whereas proteins derived from plasma (albumin and RBP) show nearly no variation. The same pattern of excretion, although less pronounced, was observed with the prostate specific antigen (PSA), a protein exclusively of post renal origin. Semen contains also high concentrations of P1, which probably results from the washout of the urogenital tract during ejaculation. It has not yet been localized the exact site of P1 secretion in the male urogenital tract. The protein was not detected in homogenates of kidney, prostate, testis, epididymis, urethra or seminal vesicles.

The urinary excretion of P1 by healthy women is very low but like in men, it shows variations, which are related to the reproductive function. The concentrations of P1 in urine are the lowest at puberty whereas they rise during pregnancy. Two pregnant women (2nd trimester) have been shown to have P1 values in urine higher than 500 μg/l i.e., 100-times the median value in this age group. This effect cannot be accounted for by an impaired tubular reabsorption since the renal handling of albumin, RBP and 2-microglobulin was normal in these women. Elevated concentrations of PI were also found in amniotic fluid.

Other Fluids. The concentrations of P1 in serum from healthy subjects lie on average between 50 and 100 μg/l and do not differ significantly between men and women. During renal insufficiency, serum P1 greatly increases (up to 1000 μg/g) and is inversely correlated with the creatinine clearance (Ccr) (r = -0.80; n = 65; Ccr between 5 and 159 ml/min), which means that P1 is eliminated from plasma by glomerular filtration. P1 is not detectable in cerebrospinal fluid, tears, or human milk and the levels in saliva were on the average still lower than that in serum. Comparison of P1 from different biological fluids. Pooled specimens of the biological fluids listed in (saliva, cerebrospinal fluid and tears excepted) were separated on Sephacryl S-200 and P1 was assayed in the eluted fractions. The chromatography of urine and serum was performed separately for males and females. In all cases, P1 eluted as a single component with an apparent molecular site around 20 kDa, which was indistinguishable from that of the purified protein. In addition, Ouchterlony double immunodiffusion analysis demonstrated a complete identity between purified protein 1 and the protein present in sputum, BAL fluid, semen and pathological urine. Since the immunoprecipitation was performed with unconcentrated samples, it also confirms the relatively high concentrations of P1 or CC 10 in these biological fluids.

Inhibition of HIV - Microtiter Antiviral XTT Assay. CEM-SS cells (or other established human cell line used in these experiments) were passaged in T-150 flasks for use in the assay. On the day preceding the assay, the cells were split 1 :2 to assure they would be in an exponential growth phase at the time of infection. On the day of the assay the cells were washed twice with tissue culture medium and resuspended in fresh tissue culture medium. Total cell and viability counting was performed using a hemacytometer and trypan blue exclusion. Cell viability was greater than 95% for the cells to be utilised in the assay. The cells were pelleted and resuspended at 2.5 x 10⁴ cells per ml in tissue culture medium. Cells were added to the drug containing plates in a volume of 50 μl.

Virus Preparation. A pretitered aliquot of virus was removed from the freezer (- 80°C) and allowed to thaw slowly to room temperature in a biological safety cabinet. The virus was resuspended and diluted into cell culture medium such that the amount of virus added to each well in a volume of 50 μL will be the amount determined to give complete cell killing at 6 days post infection. In general the virus polls produced with the 1Mb isolate of HIV required the addition of 5μL of virus per well. Pools of RF virus were five to ten fold more potent, requiring 0.5-1 μL per well.TCID₅₀ calculation by endpoint titration in CEM- SS cells indicated that the multiplicity of infection of these assays ranged from 0.005-2.5. Plate Format. The format of the test plate has been standardized. Each plate contained cell control wells (cells only), virus control wells (cells plus virus), drug toxicity control wells (cells plus drug only), drug colorimetric control wells (drug only) as well as experimental wells (drugs plus cells plus virus). XTT staining of screening plates. After 6 days of incubation at 37°C in a 5% C02 incubator, the test plates were analysed by staining with the tetrazolium dye XTT. XTT- tetrazolium is metabolised by the mitochondrial enzymes of metabolically active cells to a soluble formazan product, allowing the rapid quantitative analysis of the inhibition of HIV induced cell killing by anti HIV test substances. On day 6 post-infection plates were removed from the incubator and observed. The use of round bottomed microtiter plates allows rapid macroscopic analysis of the activity of a given test compound by the evaluation of pellet size. The results of the macroscopic observations were confirmed and enhanced by further microscopic analysis.

XTT solution was prepared daily as a stock of 1mg/mL in PBS. Phenazine methosulphate (PMS) solution was prepared at 15 mg/mL in PBS and stored in the dark at -20°C. XTT/PMS stock was prepared immediately before use by diluting the PMS 1:100 into PBS and adding 40 μl per mL of XTT solution. Fifty microliter of XTT/PMS was added to each well of the plate and the plate was reincubated for 4 hours at 37°C. Adhesive plate sealers were used in place of the lids, the sealed plate was inverted several times to mix the soluble formazan product and the plate was read spectrophotometrically at 450nm with a Molecular Device Vmax plate reader. Using an in-house computer program, %CPE reduction, % cell viability, IC₂₅, _{50 &} 95, TC ₂₅, _{50 &}g5 and other indices were calculated and the graphic results summary was displayed.

Reverse Transcriptase Activity Assay. A microtiter reverse transcriptase (RT) reaction was utilised (Buckheit et a\ (1991) AIDS research and Human Retroviruses 7: 295-302). Tritiated thymidine triphosphate (NEN)(TTP) was resuspended in distilled H₂0 at 5 Ci/mL. Poly rA and oligo dT were prepared as a stock solution which was kept at - 20°C. The RT reaction buffer was prepared fresh on a daily basis and consists of 125μl 1 M EGTA, 125 μl H₂0, 125 μl Triton X-100, 50 μl 1M Tris (pH 7.4), 50 μl 1M DTT and 40 μl 1M MgCI₂. These three solutions were mixed together in a ratio of 1 parts TTP, 2.5 parts poly rA: oligo dT, 2.5 parts reaction buffer and 4 parts distilled water. Ten microliters of this reaction mixture was placed in a round bottom microtiter plate and 15 μl of virus containing supernatent was added and mixed. The plate was incubated at 37°C for 60 minutes. Following reaction, the reaction volume was spotted onto filter mats, washed 6 times for 5 minutes each in a 5% sodium phosphate buffer, 2 times for 1 minute each in distilled water, 2 times for 1 minute each in 70% ethanol and then dried. The dried filter mat was placed in a plastic sample bag, Betaplate scintillation fluid was added and the bag was heat-sealed. Incorporated radioactivity was quantitated utilizing a Wallac Microbeta scintillation counter.

Anti-HIV activity in human cells. For isolation of adherent cells (macrophages), 3 x 10' Non-PHA stimulated peripheral blood cells are resuspended in Hanks buffered saline (with calcium and magnesium) supplemented with 10% human AB serum. The cells are placed in a 96-well microtiter plate at 37 degrees C for 2 hours. Non-adherent cells are removed by vigorously washing six times. The adherent cells are cultured for 7 days in RIM I 1640 tissue culture medium with 15% fetal bovine serum. The cultures are carefully monitored for confluency during this incubation period. Infection of the cells is performed with monocytotropic HIV-1 isolates. High titer pools of each of these viruses are harvested from infected cultures of peripheral blood adherent cells and frozen in 1.0 mL aliquots at - 80°C. Monocyte-macrophage mololayers are infected at an MOI of 0.1. Compounds to be evaluated in the monocyte-macrophage assay are added to the monolayers shortly before infection in order to maximise the potential for identifying active compounds.

At 2 days post-infection, the medium is decanted and the cultures washed twice with complete medium in order to remove excess virus. Fresh medium alone or medium containing the appropriate concentrations of drugs is added and incubation continued for an additional 5 days. XTT staining for cytotoxicity and HIV p24 ELISA assays for production of p24 core antigen are performed on Day 7 post infection. ELISA kits are purchased from Coulter. The assay is performed according to the manufacturer's recommendations. Control curves are generated in each assay to accurately quantitate the amount of capsid protein in each sample. Data is obtained by spectrophotometric analysis at 450 nm using a Molecular Devices Vmax plate reader. P24 concentrations are calculated from the optical density values by use of the Molecular Device software package Soft Max. Assay in human T-lymphocytes. Fresh human peripheral blood lymphocytes (PBL) are isolated from voluntary donors seronegative for HIV and HBV Leukophoresed blood is diluted 1 :1 with Dulbeccos phosphate buffered saline (PBS), layered over 14mL of Ficoll- Hypaque density gradient in a 50 mL centrifuge tube. Tubes are then centrifuged for 30 minutes at 600 x g. Banded PBL's are gently aspirated from the resulting interface and subsequently washed 2X with PBS by low speed centrifugation. After final wash, cells are enumerated by trypan blue exclusion and resuspended at 1 x 10⁷/mL in RPMI 1640 with 15% Fetal Bovine Serum (FBS), 2mM L-glutamine, 4 μg/mL PHA-P and allowed to incubate for 48 to 72 hours at 37°C. After incubation, PBLs are centrifuged and reset in RPMI 1640 with 15% FBS, 2 mM L-glutamine, 100 U/mL penecillin, 100 μg/mL streptomycin, 10 μg/mL gentamycin and 20 U/mL recombinant human IL-2. PBLs are maintained in this medium at a concentration of 1-2 x 10⁶/mL with bi-weekly medium changes, until used in the assay protocol.

For the PBL assay, PHA-P stimulated cells from at least two normal donors are pooled, set in fresh medium at 2 x 10⁶/mL and plated in the interior wells of a 96 well round bottom microplate at 50 μL/well. Test drug dilutions are prepared at a 2X concentration in microtiter tubes and 100 μl of each concentration is placed in appropriate wells in a standard format. 50 mL of a predetermined dilution of virus stock is placed in each test well. Wells with cells and virus alone are used for virus control. Separate plates are identically set without virus for drug cytotoxicity studies using an XTT assay system. In the standard PBL assay (MOI: 0.2), the assay was ended on day 7 following collection of cell free supernatent samples for reverse transcriptase activity assay. In the low MOI PBL assay (MOI: 0.02), supernatent samples were collected on day 6, day 11 and day 14 post infection and analysed for RT activity. Tritiated thymidine triphosphate (NEN)(TTP) was resuspended in distilled H₂0 at 5Ci/mL. Poly rA and oligo dT were prepared as a stock solution which was kept at -20oC. The RT reaction buffer was prepared fresh on a daily basis and consists of 125 μl 1M EGTA, 125 μl dH₂0, 110 μl 10% SDS, 50 μl 1M Tris (pH 7.4), 50 μl 1M DTT and 40 μl 1M MgCI₂. These three solutions were mixed together in a ratio of 2 parts TTP, 1 part poly rA: oligo dT and one part reaction buffer. Ten microliters of this reaction mixture was placed in a round bottomed microtiter plate and 15 Dl of virus containing supernatent was added and mixed. The plate was incubated at 37oC in a waterbath with a solid support to prevent submersion of the plate and incubated for 60 minutes. Following reaction the reaction volume was spotted onto pieces of DE81 paper, washed 5 times for 5 minutes each in a 5% sodium phosphate buffer, 2 times for 1 minute each in distilled water, 2 times for 1 minute each in 70% ethanol and then dried. OptifluorO was added to each sample and incorporated radioactivity was quantitated utilizing a Wallac 1450 Microbetaplus liquid scintillation counter.

Tritiated thymidine incorporation was measured in parallel cultures at day 7. Each well was pulsed with 1 μCi of tritiated thymidine and the cells were harvested 18 hours later with a Skatron cell harvester onto glass fiber filter papers. The filters were dried, placed in a scintillation vial with 1 mL of scintillation cocktail and incorporated radioactivity was quantitated on a Packard Tri-Carb 1900 TR liquid scintillation counter.

The Data obtained from the above protocol is listed in the following Tables and Graphs (1-11) . The products codes BEL16H (synthetic 24 AA sequence, with 6 histidines attached), BEL 16S (synthetic 24 AA sequence), BEL16 (recombinant 24 AA sequence, with 6 histidines attached) and BEL 16N (Native clara cell protein) are defined as follows. BEL 16H: His-His-His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe-Gln- Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala. BEL 16S: Glu-lle-Cys-Pro-Ser-Phe-Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro- Ser-Ser-Tyr-Glu-Ala-Ala. BEL 16: His-His-His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe-Gln- Arg-Val-lle-Glu-Thr-Leu-Leu-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala. BEL 16N: Met-Lys-Leu-Ala-Val-Thr-Leu-Thr-Leu-Ala-Leu-Cys-Cys-Ser Ser Aia-Ser-Ala-Glu-lle-Cys- Pro-Ser-Phe-Gln-Arg-Val-lle-Glu-Thr-Leu Ler-Met-Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala- Met-Glu-Leu-Phe-Ser-Pro-Asp-Gln-Asp-Met-Arg-Glu-Ala-Gly-Ala-Gln-Leu-Lys-Lys-Leu- Val-Asp-Thr-Leu-Pro-Gln-Lys-Pro-Arg-Glu-Ser-lle-lle-Lys-Leu.

Tables and Graphs (1-11), demonstrate the effects of the therapeutic peptides antiviral efficacy. Figures and tables 1 and 2, demonstrate how native Clara cell protein (Bel 16N) had no anti-viral activity against Ba-L in macrophages or ROJO in PBMC's. Figures and tables 3 to 5, demonstrate how the recombinant 24 AA sequence with an adjunct of 6 histidines (Bel 16) showed potent anti-viral activity against ADA in macrophages and ROJO in PBMC's. It inhibits both reverse transcriptase and p24 activity. Figures and tables 6 to 8, demonstrate how the 24 AA made synthetically in the absence of the histidine adjunct (Bel 16S) has no activity, while figures and tables 9 to 11 , demonstrate that when the 6 histidines are added to the synthetically made 24 AA (Bel 16H) the activity returns as shown against Ba-L in macrophages or ROJO in PBMCs.

Graph 1 and tables 1 and 1A show the effect of native Clara cell protein on Ba-L HIV virus (%VC) and cell viability in macrophages (%CC); Graph 2 and tables 2 and 2A show the effect of native clara cell protein on ROJO HIV virus (%VC) and cell viability (%CC) in peripheral blood mononuclear cells (PBMC) cells; Graph 3 and tables 3 and 3A show the effect of the recombinant 24 amino acid sequence plus 6 histidines on ADA HIV virus (%VC) and cell viability (%CC) in peripheral blood mononuclear cells (PBMC) cells; Graph 4 and tables 4 and 4A show the effect of recombinant 24 amino acid sequence plus 6 histidines on ROJO HIV virus (%VC) and cell viability (%CC) in peripheral blood mononuclear cells (PBMC) cells; Graph 5 and tables 5 and 5A show the effect of synthetic 24 amino acid sequence plus 6 histidines on ROJO HIV virus (%VC) and cell viability (%CC) in peripheral blood mononuclear cells (PBMC) cells (RPMI 1640 media with FBS); Graph 6 and tables 6 and 6A show the effect of synthetic 24 amino acid sequence on ROJO HIV virus (%VC) and cell viability (%CC) in peripheral blood mononuclear cells (PBMC) cells; Graph 7 and tables 7 and 7A is another embodiment of the invention showing the effect of synthetic 24 amino acid sequence on Ba-L HIV virus (%VC) and cell viability in macrophages (with NaCI) (%CC); Graph 8 and tables 8 and 8A show the effect of synthetic 24 amino acid sequence on ROJO HIV virus (%VC) and cell viability (%CC) in peripheral blood mononuclear cells (PBMC) cells (with NaCI); Graph 9 and tables 9 and 9A is another embodiment of the invention showing the effect of synthetic 24 amino acid sequence plus 6 histidines on Ba-L HIV virus (%VC) and cell viability in macrophages (%CC) (AIMV media); Graph 10 and tables 10 and 10A show the effect of synthetic 24 amino acid sequence plus 6 histidines on ROJO HIV virus (%VC) and cell viability (%CC) in peripheral blood mononuclear cells (PBMC) cells (AIMV media); Graph 11 and tables 11 and 11 A is another embodiment of the invention showing the effect of synthetic 24 amino acid sequence plus 6 histidines on on Ba-L HIV virus (%VC) and cell viability in macrophages (%CC) (RPMI 1640 media with FBS). Native Clara Cell Protein (BEL 16N) VS Ba-L IN MACROPHAGE

Table 1

Graph 1

Native Clara Cell Protein VS Ba-L IN MACROPHAGE

0 0 01 0 03₂ 0 1 0 32 1 3 2 10 3₂ 100

_o--% vc -»-% CC |

Native Clara Cell Protein (BEL 16N) VS ROJO IN PBMC

Table 2

TahlR ?A

l=NA

Graph 2

Native Clara Cell Protein VS ROJO IN PBMC

0 0 01 0 032 0 1 0 32 1 3 2 10 32 100

| _o_ % VC -»- % CC |

Recombinant 24AA SEQUENCE PLUS HISTIDINE (BEL 16) VS. ADA IN MACROPHAGE

Table 3

Table 3A

VIRUS AND CELL CONTROLS ARE PLATE AVERAGES

Graph 3

Recombinant 24AA Sequence plus Histidine VS. ADA IN MACROPHAGE

0 01 0.032 0 1 0.32 1 3 2 10 32 100

CONCENTRATION (μg/ml)

■ % VC ■ % CC |

Recombinant 24AA Sequence plus Histidine (BEL 16) VS. ROJO IN PBMC

Table 4

Table 4A

VIRUS AND CELL CONTROLS ARE PLATE AVERAGES

Graph 4

Recombinant 24AA Sequence plus Histidine VS. ROJO IN PBMC

CONCENTRATION (μg/ml)

. % VC -% CC

(RPMI 1640 MEDIA WITH FBS)

Table 5

Table 5A

VIRUS AND CELL CONTROLS ARE PLATE AVERAGES

Graph 5

Synthetic 24 AA Sequence (BEL16S) VS ROJO IN PBMC

Table 6

I ILbU (μg/fflljt !>2UU

Tl=>111

Graph 6

Synthetic 24AA Sequence VS. ROJO IN PBMC

CONCENTRATION (μg/ml)

|_D_%VC -»-%CCl

Synthetic 24AA Sequence (BEL 16S) VS Ba-L IN MACROPHAGE

Table 7

Tl=>3 24

Graph 7

24 AA Synthetic Clara Cell Protein VS Ba-L IN MACROPHAGE

0 0022 0069 021 067 2 1 655 205 64 200

CONCENTRATION (μg/ml)

| _α_% VC _»_% CC |

Synthetic 24AA Sequence (BEL16S) VS ROJO IN PBMC

Table 8

IILbU (UMJ= y44i « |IL,bU(μM)= Tl=>21

Graph 8

Synthetic 24AA Sequence VS ROJO IN PBMC

CONCENTRATION (μg/ml)

%VC ■ %CC

Synthetic 24AA Sequence plus Histidine (BEL 16H) VS. Ba-L IN MACROPHAGE

(AIMV MEDIA)

Table 9

VIRUS AND CELL CONTROLS ARE PLATE AVERAGES

IC50 (μg/ 10 3621 TC50 (μg/ml) = 34 00943

Graph 9

Synthetic 24AA Sequence plus Histidine VS. Ba-L IN MACROPHAGE AIMV

Media

0 005 0 016 0 05 0 16 0 5 1 6 16 50

CONCENTRATION (μg/ml)

- % VC -% CC

Synthetic 24AA Sequence (BEL 16H) VS. ROJO IN PBMC (AIMV MEDIA)

Table 10

VIRUS AND CELL CONTROLS ARE PLATE AVERAGES

IC50 (μg/ml 10 6208 TC50 (μg/ml) ■ >50

Graph 10

Native Clara Cell Protein (BEL 16N) VS Ba-L IN MACROPHAGE

Table 1

Table 1A

|ILbU (μg/ l)= VTCTT 11 UbU (μ_g/ lj= UU ^TO"

Graph 1

Native Clara Cell Protein VS. Ba-L IN MACROPHAGE

0 001 0032 01 032 1 32 10 32 100

|--o_%vc _»_%CC

Claims

CLAIMS What is claimed is:

2. The pharmaceutical formulation of claim 1 , wherein said compound consists of at least one of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, a part of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, the part of a sequence having at least four amino acid residues, a conservative variant of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, a conservative variant of a portion of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, the portion of a sequence having at least four amino acid residues, a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134, a part of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134, the part of a sequence having at least four amino acid residues, a conservative variant of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 or a conservative variant of a portion of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134, the portion of a sequence having at least four amino acid residues.

3. The pharmaceutical formulation of claim 1, wherein said compound consists of at least one of: a first residue consisting of: a residue of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a conservative variant of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a conservative variant of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; a residue of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; a residue of a conservative variant of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 or a residue of a conservative variant of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; and at least one adjunct residue, said adjunct residue being attached to the first residue.

4. The pharmaceutical formulation of claim 3 wherein the adjunct residue consists of one to eighty amino acids.

5. The pharmaceutical formulation of claim 4 wherein the adjunct residue consists of at least one positive charged amino acid.

6. The pharmaceutical formulation of claim 5 wherein the adjunct residue consists of one to twenty amino acids of positive charge.

7. The pharmaceutical formulation of claim 5 wherein the positive charged amino acid independently is histidine, arginine or lysine.

8. The pharmaceutical formulation of claim 3, wherein the adjunct residue is selected from the group consisting of (1) a peptide sequence residue comprising at least one amino acid residue, (2) a sugar residue, (3) a fatty acid residue and (4) a nucleotide sequence residue comprising at least one nucleotide residue.

9. The pharmaceutical formulation as claimed in claim 8, wherein the sugar residue consists of heparin.

10. The pharmaceutical formulation of claim 8, wherein the fatty acid residue is selected from the group consisting of C_η to C₂₀ fatty acid.

11. The pharmaceutical formulation of claim 10, wherein the fatty acid residue consists of diphosphatidyl choline.

12. The pharmaceutical formulation of claim 3, wherein the adjunct residue is covalently bonded to the first residue at a C-terminal or an N-terminal end of the first residue.

13. The pharmaceutical formulation of claim 1 , wherein the peptide sequence residue consists of albumin, lactoferrin, alpha fetoprotein, urinary protein, urinary protein 1 and or uteroglobin.

14. The pharmaceutical formulation of claim 1 wherein the compound is co- administered with probenecid

15. The pharmaceutical formulation of claim 1 wherein at least two or more of the compounds are present in the formulation or they are complexed together.

16. The pharmaceutical formulation of claim 1 wherein at least one compound binds antibody to clara cell protein.

17. A method comprising administering to a patient in need thereof an effective amount of the formulation of claim 1.

18. The method of claim 17, wherein the patient has a viral infection.

19. The method of claim 18, wherein the viral infection is an infection selected from the group consisting of a retrovirus infection, a togavirus infection, a flavivirus infection, a rubivirus infection, a pestivirus infection and a hantavirus infection.

20. The method of claim 18, wherein the viral infection is an infection selected from the group consisting of an infection by one or more of HIV, HTLV-1 , HTLV-3, Kaposi's Sarcoma-associated herpes virus, HHV-6, HHV-8, the viruses of the genus Molluscipoxvirus, HAV, HBV, HCV, and cytomegalovirus.

21. A method comprising administering to a patient in need thereof an effective amount of the pharmaceutical formulation of claim 1 wherein the formulation is used to (1) reduce the likelihood of viral infection in a patient who is at risk for suffering viral infection, (2) reduce the likelihood of septic shock syndrome in a patient who is about to undergo surgery, (3) treat septic shock syndrome in a patient who has recently undergone surgery (4) treat one or more autoimmune condition in a patient having an autoimmune condition, (5) ameliorate immune damage and/or disease progression in a patient having an autoimmune condition, (6) treat cancer or slow progression of cancer in a patient having a cancer or malignant condition, (7) prevent the development of cancer in a patient at risk for developing the cancer, (8) reduce the likelihood of cachexia in a patient who is about to undergo surgery or (9) ameliorate one or more symptoms associated with any of the foregoing conditions.

22. The method of claim 21 wherein the autoimmune condition is selected from the group consisting of multiple sclerosis, systemic lupus erythematoses, myasthema gravis, rheumatoid arthritis, sjogrens disease, ulcerative colitis, and diabetes.

23. The method of claim 22, wherein the cancer is selected from the group consisting of breast cancer, colon cancer, leukemia, brain cancer, lung cancer, KS and melanoma.

24. A formulation comprising an excipient and the peptide having the sequence His-His-His-His-His-His-Glu-lle-Cys-Pro-Ser-Phe-Gln-Arg-Val-lle-Glu-Thr-Leu-Leu-Met- Asp-Thr-Pro-Ser-Ser-Tyr-Glu-Ala-Ala.

25. The formulation of claim 24 wherein the formulation is a unit dosage that comprises about 5-500 mg of the peptide.

26. A pharmaceutical formulation comprising an excipient and a pharmaceutically acceptable carrier and at least one compound, said compound comprising a peptide sequence selected from the group consisting of: SEQ ID NO. 1 to SEQ ID NO. 118, conservative variants of SEQ ID NO. 1 to SEQ ID NO. 118, SEQ ID NO. 122 to SEQ ID NO. 134, and conservative variants of SEQ ID NO. 122 to SEQ ID NO. 134, any of which bind to antibody to clara cell protein.

27. The pharmaceutical formulation of claim 26, wherein said compound consists of any one of: a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a part of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, the part of a sequence having at least four amino acid residues; a conservative variant of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a conservative variant of a portion of a sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118, the portion of a sequence having at least four amino acid residues; a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; a part of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 , the part of a sequence having at least four amino acid residues; a conservative variant of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 or a conservative variant of a portion of a sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 , the portion of a sequence having at least four amino acid residues, any of which binds to antibody to clara cell protein.

28. The pharmaceutical formulation of claim 26, wherein said compound consists of at least one of: a first residue consisting of: a residue of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a conservative variant of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a conservative variant of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 1 to SEQ ID NO. 118; a residue of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; a residue of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; a residue of a conservative variant of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134 or a residue of a conservative variant of a part of a peptide sequence selected from the group consisting of SEQ ID NO. 122 to SEQ ID NO. 134; which binds to antibody to clara cell protein; and at least one adjunct residue, said adjunct residue being attached to the first residue.