Site News  |   Monitor Keywords  |   Monitor Archive  |   Organizer  |   Account Info  |

Treatment of tumors

Treatment of tumors description/claims

This application is a divisional of co-pending U.S. patent application Ser. No. 11/481,423, filed Jul. 5, 2006, U.S. Patent ______, which application claims the benefit, under 35 U.S.C. § 119(e), to provisional patent application U.S. Ser. No. 60/696,657, filed on Jul. 5, 2005, the contents of the entirety of each of which are hereby incorporated by this reference.

The invention relates generally to biotechnology, and more specifically to methods of affecting tumor growth using peptides, such as tri-mers, 4-mers, 5-mers, 6-mers, 7-mers, and methods or treating subjects with a peptide and pharmaceutical compositions containing a peptide.

Cancer is the second leading cause of human death next to coronary disease. Worldwide, millions of people die from cancer every year. In the United States alone, as reported by the American Cancer Society, cancer causes the death of well over a half-million people annually, with over 1.2 million new cases diagnosed per year.

Worldwide, several cancers stand out as the leading killers. In particular, carcinomas of the lung, prostate, breast, colon, pancreas, and ovary represent the primary causes of cancer death. These and virtually all other carcinomas share a common lethal feature. With very few exceptions, metastatic disease from a carcinoma is fatal. Moreover, even for those cancer subjects who initially survive their primary cancers, common experience has shown that their lives are dramatically altered. Many cancer subjects experience strong anxieties driven by the awareness of the potential for recurrence or treatment failure. Many cancer subjects also experience physical debilitations during or following treatment. Furthermore, many cancer subjects experience a recurrence.

Due to the recurrence rates and side effects of current cancer treatments, improved cancer treatments represent a great need in society. Preferably, those treatments are small molecules that are easily adsorbed by the body, cheap and easy to manufacture, effective, and do not have many of the side effect associated with current cancer treatments.

Where it was generally thought that the smallest breakdown products of proteins have no specific biological function on their own, it now emerges that the body may utilize the normal process of proteolytic breakdown to generate important compounds. In particular, certain short breakdown products of hCG (i.e., short peptides, derivates, or functional analogues which can easily be synthesized and used in a pharmaceutical composition) can be used to limit the progression of tumors.

The current invention relates to understanding and/or predicting the body's innate way of responding to small molecules and builds on insights reported in PCT International Publications WO99/59617, WO01/72831, and WO03/29292, the contents of the entirety of all of which are incorporated herein by this reference. These applications describe small gene-regulatory peptides that are present in pregnant women that are derived from proteolytic breakdown of placental gonadotropins, such as hCG. These breakdown products are often only about three to six amino acids long and were shown to have unsurpassed immunological activity that is exerted by regulating expression of genes encoding inflammatory mediators such as cytokines. Surprisingly, it was found that breakdown of hCG provides a cascade of peptides that helps maintain a pregnant woman's immunological homeostasis. These peptides balance the immune system to assure that the mother stays immunologically sound while her fetus does not get prematurely rejected during pregnancy, but instead is safely carried until its time of birth. Other peptides known in the art have the antigenic binding activity of human chorionic gonadotropin (hCG). See, e.g., U.S. Pat. No. 5,380,668 to Herron (Jan. 10, 1995), the contents of the entirety of which are incorporated by this reference. The oligopeptides disclosed therein are disclosed generally for use in diagnostic methods.

Other patents and patent applications, relate to the use of short polypeptides to modulate biological systems. For example the patents an applications to Gallo et al. (e.g., U.S. Pat. No. 5,677,275 (corresponding to WO 96/04008 A1), U.S. Pat. No. 5,877,148 (also corresponding to WO 96/04008 A1), WO 97/49721 A1, U.S. Pat. No. 6,319,504 (corresponding to WO 97/49373), U.S. Patent Application 2003/0049273 A1 (also corresponding to WO 97/49373), U.S. Pat. No. 5,968,513 (corresponding to WO 97/49418), U.S. Pat. No. 5,997,871 (corresponding to WO 97/49432), U.S. Pat. No. 6,620,416, U.S. Pat. No. 6,596,688, WO 01/11048 A2, WO 01/10907 A2, and U.S. Pat. No. 6,583,109), disclose various oligopeptides and their use in, among other things, “inhibiting HIV infection,” “treating or preventing HIV infection,” “treating or preventing cancer,” “treating or preventing a condition characterized by loss of body cell mass,” “treating or preventing a condition associated with pathological angiogenesis,” “treating or preventing hematopoietic deficiency,” “ex vivo gene therapy,” “expanding blood cells in vitro,” and/or “providing blood cells to a subject.”

In an exemplary embodiment, the present invention provides a method for identifying one or more peptides; and/or determining the activity of one or more peptides, comprising, for instance, screening a peptide to determine the activity of the peptide; analyzing the results; and/or identifying one or more peptide having anti-tumor activity.

In a further embodiment, derivates or functional analogues of anti-tumor peptides may be created.

The invention provides methods for reducing tumor growth by administering a pharmaceutical composition comprising a pharmacologically effective amount of at least one anti-tumor peptide or a derivative or a functional analogue thereof together with a pharmaceutically acceptable diluent to the subject. A particular useful pharmaceutically acceptable diluent is sterile water or an isotonic salt solution such as 0.9% saline or phosphate buffered salt (PBS). In a preferred embodiment, the invention provides the treatment of a subject suffering or believed to be suffering from cancer by mucosal, preferably oral administration of a pharmaceutical composition comprising a pharmacologically effective amount of two or more anti-tumor peptides, derivatives, or functional analogues thereof together with a pharmaceutically acceptable diluent to the subject.

The invention thus provides use of an anti-tumor peptide pharmaceutical composition for application to a subject for reducing tumor size and/or inhibiting tumor progression. Useful examples of such an anti-tumor peptides can be selected from the group of oligopeptides LQG, LAG, LQGV (SEQ ID NO:1), AQGV (SEQ ID NO:2), LAGV (SEQ ID NO:3), VLPALP (SEQ ID NO:4), and functional analogues or derivatives thereof. Functional analogues can, for example, be found in urinary fractions derived from pregnant woman or in commercial preparations of hCG; at least in those commercial preparations that contain substantial amounts of breakdown products of hCG.

A preferred size of an anti-tumor peptide for inclusion in a pharmaceutical composition according to the invention is at most 15 amino acids, preferably at most seven amino acids, although much smaller molecules of 3, 4, 5, or 6 amino acids in length are particularly effective.

The invention also provides use of a peptide of smaller than 30 amino acids for the production of a pharmaceutical composition for the treatment a subject suffering from or believed to be suffering from cancer. It is preferred that said peptide be smaller than 15 amino acids. When peptides are used repeatedly, for example, as is provided herein for the treatment of cancer, from a safety viewpoint it is preferred that said peptide is smaller than seven amino acids, such a peptide generally not binding to the MHC receptors, thereby decreasing the risk of the development of autoimmunity initiated by an immune response against administered peptide.

Subjects suffering from cancer will already benefit from the anti-inflammatory properties of some of the small peptides identified herein, but surprisingly most benefit will come from the anti-cell cycle activity of the small peptides, notably of the 3- and 4-mer peptides at dosages of above 1 mg/kg, preferably of above 5 mg/kg, more preferably of above 10 mg/kg body weight. Considering the low immunogenic nature of the small peptides (i.e., those of three to four aa), dosing to up to 100 mg/kg with small peptides, and in some cases when need for treatment is determined to be acute considering the condition of the subject in need of treatment, of up to 200 mg/kg, 500 mg/kg or even 1 g/kg will be possible.

Furthermore, it is particularly useful that subjects in need of treatment for cancer can now be treated via a subcutaneous or intra-muscular injection, thereby allowing self-treatment with an autoinjector or treatment by non-trained or non-medical personnel.

Other peptides, especially 3- or 4-mer peptides, can be found by testing for anti-cell cycle activity in proliferation assays, for example, by using a plant growth assay as provided herein. Use of a peptide for the production of a pharmaceutical composition for the treatment a subject suffering from or believed to be suffering from cancer wherein said peptide consists of two to six amino acids is herein particularly provided. From the viewpoint of preventing adverse reactions, such as anaphylactic shock, it is thus preferred that the pharmaceutical composition comprises a peptide that consists of two to six amino acids, more preferably consists of three to five amino acids, and most preferably consists of three or four amino acids. If only from the viewpoint of activity, based on a general insight that activity is broader with increasing peptide size, if only to withstand full proteolysis (after administration) longer whereby metabolic fragments of three aa still have activity, it is herein preferred that said peptide consists of four amino acids.

• Provisional Patent
• Utility Patent

• What Is a Patent?
• What Is a Trademark or Servicemark?
• What Is a Copyright?
• Patent Laws