SYNTHETIC IMMUNOACTIVE PEPTIDES HAVING IMMUNOMODULATING AND THERAPEUTIC ACTIVITIES

Abstract: Synthetic peptides which are effective in the therapy of immunodeficiencies, immunosuppression and T-cell subset deviations, and related ailments.

Description: Description Synthetic Immunoactive Peptides Having Immunomodulating and Therapeutic Activities Technical Field The present invention relates, generally, to synthetic immunoactive peptides having immunodulating and therapeutic activities and use of such peptides in pharmaceuticals. More particularly, the present invention relates to chemically synthesized immuno- active peptides useful in immunotherapy for regulation of T-cell dependent immunity. Background Art It is generally known in the prior art that a great number of disorders in humans, as well as animals, are associated with decreased immunity or immunodeficiency. Various degrees of altered levels of immunity are found in oncologic and hematalogic diseases, aging, etc. As a result of immunological dysfunction, various infections, neoplasias and accerated metastasizing may be observed in persons suffering from such disorders. The crucial role of thymus-dependent immunity in the function of the immune system is well- established. Recently, a number of biologically active polypeptides have been isolated from the thymus and, at least partially, characterized. Among such polypeptides are various thymosins, thymopoietins and thymic serum factor. These results are detailed in Cardarelli, Nate P., The Thymus in Health and Senescence. CRC Press (1989); Gol*dstein, Allan L. , Thymic Hormones and Lymphokines: Basic Chemistry and Clinical Applications. NY, Plenum Press (1989); and, Gideon Goldstein et al., NY Liss (1987). Fraction V, the uncharacterized mixture of poly¬ peptides from calf thymus extract, having relatively high amounts of alpha-, beta- and gamma-thymosins and related polypeptides, has proven to be useful from immunomodulation in in vitro and in vivo tests, as summarized in Aiuti, F. and Wigzell, H. , Thymus. Thymic Hormones, and T-Lymphocytes, Proceedings of the Serono Symposium, V. 38 (Academic Press 1989.) The potential effectiveness of Fraction V as an immunomodulating drug has been disclosed in H. Strausser, U.S. Patent No. 4,444,757, issued April 24th, 1984. The clinical use of the foregoing preparations has been limited by: 1. The impossibility of obtaining an adequate quantity for studies, as well as the need for using a significant amount of autological material of thymuses of newborn children: 2. The impossibility of precise biochemical identification of extracts; and, 3. An immune response to the xenogenic or allogenic proteins from thymic extracts. In summary, the use of purified natural or recombinant polypeptides for immunotherapy is limited by the limited source of biologically active components, as well as the immunological and bio- chemical difficulties in their purification. Synthetic peptides avoid these drawbacks. Different immunologically active synthetic peptides, related to either natural thymosins alpha 1, beta 3 and beta 4, as modified sequences, have been disclosed in, for example, S. Wang, U.S. Patent No. 4,116,951, issued September 26th, 1978; T. Low et -4- al., U.S. Patent No. 4,395,404, issued July 26th, 1983; and, C. Birr et al., U.S. Patent No. 4,612,365, issued September 16th, 1986. Additionally, the active synthetic peptide of thymopoie in has been described in G. Goldstein et al., Science. 1979, 204. p. 1309. This peptide sequence has been disclosed in G. Goldstein et al., U.S. Patent No. 4,190,646, issued February 1980, and modified sequences having similar activity were disclosed in G. Goldstein et al., U.S. Patent No. 4,201,886, issued April 14th, 1981. These peptide sequences induce differentiation of lymphocytes into mature T-cells expressing specific markers, support the delicate equilibrium of helper and suppressor T-cells, stimulate the previously-diminished immune response and suppress excessive autoimmune activity to various auto- antigens. Nevertheless, the overall biological activities of presently known synthetic peptides have proven to be insufficient for clinical use, as detailed, for example, in B. K. Kantharia et al., "Thymopentin (TP-5) in the treatment of Rhumatoid arthritis," Br. J. Rheumatol. 1989, 28(2) . pp. 118-123; J. A. Hansen, J. E. Sanders, R. Stuart, "Use of thymic grafts of thymic factors to augment immunologic recovery after bone marrow transplantation: brief report with 2 - 12 years follow-up. Bone marrow transplant. 1980, pp. 424-436. Pentapeptide sequences with thymopoietin-like activity and increased resistance to enzymatic degradation in biological fluids were created and disclosed in G. Goldstein et al. , U.S. Patent No. 4,505,853, issued March 19th, 1985, however, their biological activity was comparable only with activity of parental peptide sequences. In order to overcome the weak activities of the thymopoietin-derived peptide to the #32-36 sequence, an additional peptide from alpha-1 thymosin was added. This further procedure, however, failed to increase the biological activity of the parent sequences, as detailed in M. Mokotoff et al. , "Thymosin-like peptides as potential immunostimu- lants. Synthesis via the polymeric-reagent method," J. Med. Chem.. 1990, 33(1), pp. 354-360. Additional prior art known to the inventor, but which has failed to overcome the difficulties encountered in the production of immunothera- peutically active peptides, includes G. Goldstein et al., U.S. Patent No. 4,002,740, issued January 11th, 1977; W. McGregor, U.S. Patent No. 4,082,737, issued April 4th, 1978; G. Goldstein, U.S. Patent No. 4,124,700, issued November 7th, 1978; A. Goldstein et al., U.S. Patent No. 4,297,276, issued October 27th, 1981; C. Birr et al., U.S. Patent No. 4,353,821, issued October 12th, 1982; G. Heavner, U.S. Patent No. 4,369,137, issued January 18th, 1983; B. Horecker, U.S. Patent No. 4,374,197, issued February 15th, 1983; G. Goldstein et al. , U.S. Patent No. 4,397,842, issued August 9th, 1983; C. Birr et al. , U.S. Patent No. 4,466,918, issued August 21st, 1984; C. Birr et al., U.S. Patent No. 4,470,926, issued September 11th, 1984; A. Felix et al. , U.S. Patent No. 4,504,415, issued March 12th, 1985; A. Felix et al., U.S. Patent No. 4,517,119, issued May 14th, 1985; B. Horecker, U.S. Patent No. 4,659,694, issued April 21st, 1987; B. Horecker, U.S. Patent No. 4,716,148, issued December 29th, 1987; and, C. Birr et al., U.S. Patent No. 4,910,296, issued March 20th, 1990. It is clear that if the difficulties encountered in the production of immunotherapeutically active peptides could be overcome, a major advancement in the treatment of various diseases would be achieved. Thus, a great need exists for the creation of biologically active peptides which can be used for the clinically effective correction of immuno¬ deficiencies and immunosuppressions associated with different pathological conditions. Disclosure of Invention It is, therefore, an object of the present invention to provide a series of synthetic peptides which are effective in the therapy of immunodeficien¬ cies, immunosuppression and T-cell subset deviations, and related ailments. It is an additional object of the present invention to provide a series of synthetic peptides which have a biological activity which is several hundred times more effective than presently known immunologically-active sequences. It is, yet, a further object of the present invention to provide synthetic peptides which are non-toxic to humans, even when administered in doses which are several thousand times higher than effective dose levels. It is an additional object of the present invention to provide a series of synthetic peptides which overcome the disadvantages inherent in the prior art and with similar substances found in nature. The foregoing and related objects are achieved by linear and cyclized peptide compounds constructed by combination and/or overlapping of the sequences: Ai Bi X B2 A2 , A3 B3 X A B _ , Bs As X Ae Be , B7 7 X Be As , A9 B9 , Ai o Ai l , B10 A12 and/or B1 1 B12 , wherein, X is a hydrophobic or neutral amino acid independently selected from the group consisting of Ala, D-Ala, Gly, D-Gly, Ile, 5-Ile, Leu, D-Leu, Met, D-Met, Phe, D-Phe, Pro, #-Pro, Sar, D-Sar, Ser, D-Ser, Tre, D-Tre, Trp, D-Trp, Val and D-Val; Ai through A12 are, independently, neutral or positively-side-chain-charged amino acids independently selected from the group consisting of Ala, D-Ala, Arg, D-Ar , Asp, D-Asp, Glu, D-Glu , Gly, D-Gly, His, J-His, Ile, D-Ile, Leu, D-Leu, Met, D-Met, Phe, D-Phe, Pro, D-Pro, dehydro Pro, Sar, D-Sar, Ser, D-Ser, Tre, D-Tre, Trp, D-Trp, Val and D-Val; and, Bi through B12 are, independently, neutral or negatively-side-chain-charged amino acids independently selected from the group consisting of Ala, D-Ala , Asp, D-Asp, Glu, D-Glu, Gly, D-Gly, Ile, D-Ile, Leu, D-Leu, Met, D-Met. Phe, D-Phe, Pro, D-Pro, dehydro Pro, Sar, D-Sar, Tre, D-Tre, Tyr, D-Tyr, Val, P-Val, L-2- amino- glutaryl, D-2-aminoglutaryl, -2-aminoadiphyl, Z-2-aminoadiphyl, -2-aminopimelyl and _>-2-aminopimelyl. The foregoing peptides, in accordance with the present invention, may be acylated and/or amidated. The foregoing generic formula includes the following sequences of amino acids in accordance with the foregoing definitions for "A," "B" and "X"; 1. A1A2B2XA3B3 2. A1A2XB2A2A3 3. A1B1XB2A2A3 4. B1A1XB2A2A3 5. B1B2A2XA3B3 6. B1B2A2XB3A3 7. A1B1XA2B2B3 8. B1A1XA2B2B3 9. A1B2A2XA3B3 10. A1B2A2XB3A3 11. A1B1XB2A2B3 12. B1A1XB2A2B3 13. B1A2B2XB3A3 14. B1A2B2XA3B3 15. A1B1XA2B2A3 16. B1A1XA2B2A3 17. A1A2A3B3XB4A4 18. Ai A2 A3 B3 XA4 B4 19. Ai A2 B3 A3 XA4 B4 20. Ai A2 B3 A3 XB4 A 21. Ai Bi XB2 A2 A3 A4 22. Ai Bi XA2 B2 A3 A4 23. B1A1XA2B2A3A4 24. B1A1XB2A2A3A4 25. Bi B2 A3 B3 XB4 A4 26. Bi B2 A3 B3 XA4 B4 27. Bi B2 B3 A3 XA4 B4 28. Bi B2 B3 A3 XB4 A4 29. Ai Bi XB2 A2 B3 B3 30. A1B1XAB2B3B4 31. B1A1XA2B2B3B4 32. B1A1XB2A2B3B4 33. Ai Bi A2 B2 XB3 A3 34. Ai Bi A2 B2 XA3 B3 35. Ai Bi B2 A2 XA3 B3 36. Ai Bi B2 A2 XB3 A3 37. A1B1XB2A2A3B3 39. Ai Bi XA B2 A3 B3 39. B1A1XA2B2A3B3 40. Bi Ai XB2 A2 A3 B3 41. BiAiA2B2XB3A3 42. BiAlA2B2XA3B3 43. BiAiB2A2XA3B3 44. BiAiB2A2XB3A3 45. AiBiXB2A2 B3A3 46. AiBiXA2 B2 B3A3 47. BlAiXA2 B2 B3A3 48. BiAiXB2A2 B3A3 49. BiAiA2 B2XB3A3A4B4 50. Ai BiA2 B2XB3A3B4A4 51. BiAiA2 B2XA3B3A4B4 53. BiAiB2A2XA3B3A4B4 53. AiBi B2A2XA3 B3B4A4 54. AiBiA2 B2XA3B3B A4 55. BiAiB2A2XB3A3A4B4 56. AiBiB2A2XB3A3B4A4 57. BiAiA2B2XB3A3B A4 58. Ai BiA2 B2XB3A3A4B4 59. BiAiA2B2XA3B3B4A4 60. AiBiA2 B2XA3B3A4B4 61. BiAi B2A2XA3B3B4A4 62. AiBiB2A2XA3B3A4B4 63. BiAiB2A2XB3A3B4A4 64. Ai Bi B2A2XB3A3A4B4 65. AiB2XA2A2XA3B3 66. Ai BiXB2A2XB3A3 67. AiBiXA2 B2XB3A3 68. BiAiXA2B2XB3A3 69. BiAiXA2B2XA3B3 70. BiAiXB2A2XA3B3 71. Ai BiXB2A2A3B3XB4A4 72. Ai BiXA2 B2A3B3XA4B 4 73. BiAiXA2 B2 B3A3XA4 B4 74. BiAiXB2A2 B3A3XB4A4 75. AiBiXB2A2A3B3XA4 B4 76. AiBiXA2 B2A3B3XB4A4 77. Ai BiXB2A2B3A3XA4B4 78. BiAiXA2 B2A3B3XB4A4 79. AiBiXB2A2 B3A3XB4A4 80. BiAiXB2A2A3B3XB4A4 81. Ai BiXA2 B2B3A3XB4A4 82. BiAiXB2A2A3B3XA4 B 4 83. AiBiXA2B2B3A3XA4B4 84. BiAlXA2B2A3B3XA 4 B 85. BiAiXA2 B2B3A3XB4A4 86. BiAiXB2A2 B3A3XA4 B4 The present invention should be understood as encompassing pharmaceutically acceptable acid or base salts, as well as the free peptides generically described above and which are detailed hereinafter. For the purposes of achieving the objects of the present invention, amino acid sequence No. 41 provides the most effective peptides. Amino acid sequences Nos. 49 and 59 have also been found to be very effective. It was surprisingly discovered that the peptides of the invention, as defined above, express immuno¬ modulating activity, with many such peptides expressing a more powerful immunodulating activity than known natural, or naturally modified, amino acid sequences. The compositions to be administered to a patient in the treatment of immunodeficiencies, immunosuppression, T-cell subset deviations and for the enhancement of vaccinations, etc., is to include one or more of the foregoing peptides in combination with an appropriate solubilizer. Suitable additives known to those skilled in the art, e.g., carriers, preservatives and viscosity modifiers, may be added to the compounds of the invention as required. The synthetic immunologically-active peptides of the present invention are, for example, for parenteral use, direct intranasal, ear, eye, intra- vaginal or rectal instillation and application to intact or injured conjunctive, mucosa or skin, in order to accomplish the normalization of immune responses. The preparations are to be used either locally or systemically in order to induce immuno- modulation, enhance the effect of vaccination and achieve other goals of immunotherapy. Preferred peptides of the present invention are those wherein: Ai through An are, independently, Arg, Asn, Gin, Lys, Phe or Val; Bi through Bn are, independently, Asp, Glu, Tyr, Phe or Val ; X is Ala, Gly, Ile, Leu, Phe or Val. Most preferred peptides coming within the scope of the present invention contain either balanced side chain charges of the sequences which are symmetical relative to X or uncompensated opposite side chain charges relative to X. For protection against amino- and carboxypep- tidases, peptides may be acylated, amidated or cyclized during synthesis. Examples of peptides falling within the scope of the present invention, which have been found to be particularly effective include: Arg-Asp-Lys-Asp-Val-Tyr-Arg Lys-Asp-Lys-Asp-Val-Tyr-Lys Lys-Glu-Lys-Asp-Val-Tyr-Lys Arg-Glu-Arg-Asp-Val-Tyr-Arg Lys-Glu-Leu-Tyr-Arg-Lys-Glu Lys-Glu-Leu-Glu-Lys-Lys-Glu Arg-Glu-Leu-Glu-Arg-Arg-Glu Lys-Asp-Val-Asp-Lys-Lys-Asp Lys-Asp-Leu-Glu-Lys-Lys-Glu Tyr-Arg-Lys-Asp-Val-Tyr-Arg-Lys-Glu Tyr-Arg-Lys-Glu-Leu-Glu-Lys-Lys-Glu Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Lys-Glu Tyr-Arg-Lys-Glu-Leu-Tyr-Arg-Glu-Lys Tyr-Arg-Lys-Asp-Val-Tyr-Arg-Lys-Asp-Val-Tyr-Arg Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Lys-Glu-Leu-Tyr-Arg Glu-Arg-Lys-Glu-Leu-Tyr-Arg-Lys-Glu-Leu-Tyr-Arg Examples of peptides synthesized in accordance with the present invention, which have been found to be most effective in immunotherapy, include: Arg-Asp-Lys-Asp-Val-Tyr-Arg Lys-Asp-Lys-Asp-Val-Tyr-Lys Lys-Glu-Lys-Asp-Val-Tyr-Lys Arg-Glu-Arg-Asp-Val-Tyr-Arg Lys-Glu-Leu-Tyr-Arg-Lys-Glu Lys-Glu-Leu-Glu-Lys-Lys-Glu Arg-Glu-Leu-Glu-Arg-Arg-Glu Lys-Asp-Val-Asp-Lys-Lys-Asp Lys-Asp-Leu-Glu-Lys-Lys-Glu Tyr-Arg-Lys-Asp-Val-Tyr-Arg-Lys-Glu Tyr-Arg-Lys-Glu-Leu-Glu-Lys-Lys-Glu Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Lys-Glu Tyr-Arg-Lys-Glu-Leu-Tyr-Arg-Glu-Lys Tyr-Arg-Lys-Asp-Val-Tyr-Arg-Lys-Asp-Val-Tyr-Arg Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Lys-Glu-Leu-Tyr-Arg Glu-Arg-Lys-Glu-Leu-Tyr-Arg-Lys-Glu-Leu-Tyr-Arg Examples of peptides synthesized in accordance with the present invention, which have been found to be most effective in immunotherapy, include: Glu-Arg-Lys-Glu-Leu-Tyr-Arg Tyr-Arg-Lys-Asp-Val-Tyr-Arg Tyr-Arg-Lys-Glu-Leu-Tyr-Arg Glu-Arg-Lys-Asp-Val-Tyr-Arg Cyclized peptides synthesized in accordance with the present invention, and which are preferred for their effective in immunotherapy, include: -Tyr-Arg-Lys-Asp-Val- -Tyr-Arg-Lys-Glu-Val- -Glu-Arg-Lys-Glu-Val- -Glu-Lys-Lys-Glu-Leu- -Glu-Lys-Lys-Asp-Leu- -Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Lys-Asp-Val- _Tyr-Lys-Lys-Glu-Leu-Tyr-Arg-Lys-.Glu-Leu_ -Tyr-Arg-Lys-Glu-Leu-Tyr-Arg-Lys-Glu-Leu- ■ Tyr-Arg-Lys-Asp-Val-Tyr-Arg-Lys-Asp-Val- -Glu-Lys-Lys-Glu-Leu-Glu-Lys-Lys-Glu-Leu- Other peptides encompassed within the scope of the present invention and which have effective levels of immunotherapeutic activity, though not as great as those peptides listed above, further include: Arg-Lys -Asp-Val- ■ Lys-Tyr ; Arg-Lys- ■ Asp-Val- ■ Arg-Tyr ; Arg-Lys -Asp-Val- • Phe-Glu ; Arg-Glu- •Glu-Val- • Phe-Glu ; Arg-Lys -Asp-Val- ■ Tyr-Arg ; Arg-Asn- ■ Asp-Val- • Tyr-Arg ; Arg-Lys -Glu-Leu- ■ Tyr-Arg ; Arg-Gln- •Glu-Leu- •Tyr-Arg ; Arg-Lys -Asp-Val- ■ Tyr-Lys ; Arg-Asn- •Asp-Val- ■ Tyr-Lys ; Arg-Lys -Glu-Leu- ■ Tyr-Lys ; Arg-Gln- •Glu-Leu- Tyr-Lys ; Arg-Lys -Asp-Val- •Glu-Arg ; Arg-Lys- •Glu-Leu- •Glu-Arg ; Arg-Lys -Glu-Val- Glu-Arg ; Arg-Phe- ■ Leu-Tyr- Arg-Asp ; Phe-Tyr -Arg-Leu- Arg-Tyr ; Glu-Tyr- ■ Arg-Leu- Arg-Tyr ; Glu-Tyr ■ Arg-Leu- Tyr-Arg ; Lys-Glu- ■ Leu-Gln- Glu-Glu ; Lys-Asp -Val-Arg- Tyr-Tyr ; Lys-Asp- •Val-Lys- Phe-Glu ; Lys-Asp -Val-Arg- Phe-Glu ; Lys-Asp- ■ Val-Arg- Tyr-Asp ; Arg-Tyr-Asn-Val-Tyr-Arg ; Arg-Tyr-Gln-Leu-Tyr-Arg ; Arg-Tyr-Asn-Val-Tyr-Lys ; Arg-Tyr-Gln-Leu-Tyr-Lys ; Arg-Glu-Lys-Leu-Tyr-Arg ; Gln-Glu-Lys-Leu-Tyr-Ar ; Gln-Asp-Lys-Leu-Tyr-Arg ; Asn-Asp-Lys-Leu-Tyr-Arg ; Lys-Tyr-Val-Tyr-Arg-Asp ; Tyr-Arg-Asp-Val-Tyr-Arg ; Tyr-Lys-Asp-Val-Tyr-Lys ; Tyr-Lys-Glu-Leu-Tyr-Arg ; Asp-Asn-Tyr-Val-Tyr-Arg ; Asp-Asn-Tyr-Leu-Glu-Arg ; Asp-Asn-Tyr-Leu-Glu-Gln ; Arg-Asn-Lys-Asp-Val-Tyr-Arg ; Arg-Gln-Arg-Glu-Leu-Tyr-Arg ; Arg-Asn-Arg-Tyr-Leu-Tyr-Arg ; Arg-Asp-Val-Tyr-Arg-Gln-Asn ; Lys-Asp-Val-Tyr-Arg-Gln-Asn ; Arg-Asp-Val-Tyr-Lys-Gln-Asn ; Asp-Glu-Lys-Glu-Leu-Tyr-Arg ; Glu-Glu-Lys-Asp-Val-Tyr-Ar ; Asp-Glu-Gln-Glu-Leu-Phe-Arg ; Gln-Asp-Val-Tyr-Arg-Glu-Asp ; Gln-Glu- Asn- Asp-Val-Glu-Gln ; Asn-Asp-Gln-Glu-Leu-Glu-Gln ; Asn-Asp-Lys-Asp-Val-Asp-Lys ; Gln-Glu- sp-Lys-Leu-Tyr-Ar ; Arg-Glu-Asp-Lys-Leu-Tyr-Ar ; Arg-Glu-Asp-Arg-Leu-Tyr-Arg ; Arg -Asp-Glu-Arg- Leu-Tyr- Arg; Arg -Glu-Tyr-Arg- Leu-Tyr- Arg: L s' -Glu-Tyr-Arg Leu-Tyr- Ar Lys -Asp-Val-Tyr Arg-Arg- ■ Tyr; Lys -Asp-Val-Tyr Arg-Lys- •Tyr; Lys -Asp-Val-Tyr Arg-Lys- Asp; ys' -Glu-Leu-Glu Arg-Lys- ■ Glu; Arg' -Asp- Val -Asp Lys-Lys- •Asp; ys' -Asp-Leu-Glu Lys-Lys- Asp; 10 L s' -Glu-Leu-Lys Glu-Lys- Glu: L s' -Asp-Leu-Lys Glu-Lys- Asp; Glu -Arg-Lys-Asp Val-Tyr- •Arg: Glu- -Lys-Lys-Asp Val-Tyr- Arg; Asp- -Arg-Lys-Asp Val-Tyr- Arg: 15 Lys- -Glu-Leu-Lys Glu-Tyr- Arg Lys- -Asp-Val-Lys Glu-Tyr- Lys: Glu-Lys- ■ Lys-Glu-Leu Glu-Lys- Lys-Glu; Glu-Lys- •Lys-Glu-Leu Tyr-Arg- Arg-Tyr; Glu-Lys- -Lys-Glu-Leu Arg-Tyr- Tyr-Arg ; 20 Tyr-Arg- -Lys-Asp-Val Lys-Tyr- Tyr-Arg; Glu-Lys- -Lys-Glu-Leu Tyr-Arg- Tyr-Arg; Glu-Lys- -Lys-Glu-Le Tyr-Arg- Glu-Arg; Glu-Lys- -Lys-Glu-Leu Tyr-Arg- Glu-Arg; Glu-Lys-Lys-Glu-Leu-Glu-Gln-Tyr-Arg ; Glu-Lys-Lys-Glu-Leu-Glu-Gln-Asp-Asn; Lys-Glu-Glu-Lys-Leu-Glu-Lys-Lys-Glu; Lys-Asp-Asp-Lys-Leu-Tyr-Arg-Gln-Glu; Gln-Glu-Asp-Lys-Leu-Tyr-Arg-Gln-Glu ; Gln-Glu-Asp-Lys-Leu-Tyr-Arg-Gln-Glu; Arg-Tyr-Leu-Arg-Tyr-Leu- Tyr-Arg ; Arg-Tyr-Leu-Lys-Glu-Leu-Tyr-Arg ; Tyr-Arg-Gly-Lys-Glu-Leu-Tyr-Arg ; Arg-Tyr-Leu-Tyr-Arg-Lys-Asp-Val-Tyr-Arg ; and, Arg-Tyr-Leu-Glu-Lys-Lys-Glu-Leu-Tyr-Arg . Linear peptides of the present invention may be synthesized via procedures generally known to those skilled in the art and which are of wide use at present. M. Bodanszky and A. Bodanszky, Peptide Chemistry: A Practical Textbook. Springer-Verla , N.Y. (1988); M. Bodanszky and A. Bodanszky, The Practice of Peptide Synthesis. Springer-Verla . N.Y. (1989). All linear peptides of the present invention, for example, may be synthesized by the solid phase method utilizing peptide synthesizers which are commercially available through, for example, Applied Biosystems, Inc., Foster City, California, U.S.A., and t-Boc chemistry. In practice, crude preparations of peptides were purified by low pressure column ion-exchange chromatography following preparative ion-exchange as reverse phase HPLC. Purity of the final products had been analyzed by analytical reverse phase HPLC using ODS-columns and structure was verified by amino acid analysis. Purity of peptides synthesized varied from 94.2% to 99.2%. Cyclized peptides synthesized in accordance with the present invention may be synthesized in accordance with the following: Dicarbonic amino acids were attached to a resin via estification of a side chain carboxyl group and deprotected, Aminoacid-O-nitrophenol esters and aminoacid-O-succinimide esters were coupled directly to the deprotected alpha-amino groups of the growth peptide in the desired sequence to produce C-terminal and N-terminal deprotected peptide-resin. These resin-bounded peptides were cyclized using dicyclo- hexyl carbodiimide, cleaved and side chain deprotected following purification. Aminoacidic analysis or NMR spectra may be utilized to confirm that the desired cyclized peptide has been produced. Other objects and features of the present invention will be described in connection with the accompanying drawing figures and tables, which further illustrate the invention. It should, however, be recognized that the accompanying figures and tables are intended solely to illustrate the invention and are not intended as a means for defining the scope of the invention. Brief Description of the Drawing Figures/Tables Figures 1 - 5 (i.e., Tables 1 - 5) present experimental data illustrating the use and effective¬ ness of the peptides of the present invention. Detailed Description of the Preferred Embodiments Turning now, in detail, to an analysis of the preferred embodiments and experimental data, conducted by the inventor, which illustrates the immunotherapeutic activity of the peptide compounds of the present invention. Initially, a suboptimal amount of phyto- hemagglutinin from Phaseolus vulgaris was utilized in experimentation. Phytohemagglutinin is a non¬ specific stimulator of T-lymphocyte activation, which does not induce 3 H-thymidine uptake by peripheral blood lymphocytes in sub-optimal amounts. Peptides of the present invention were added in a wide range of concentrations to lymphocyte cultures and caused a dramatic increase of 3 H-thymidine incorporation into cell DNA. As shown in Table 1, the peptides of the invention are over 100 to 1000 times more active than other known immunologically-active sequences. The peptides tested in Table 1 were as follows: Peptides Amino Acid Sequence Thymopoietin NN32-36 Arg-Lys-Asp-Val-Tyr Thymosin alpha-1 N23-27 Val-Glu-Glu-Ala-Glu Peptide (a) Arg-Lys-Asp-Val-Tyr-Arg Peptide (b) Arg-Lys-Asp-Val-Tyr-Lys Peptide (c) Glu-Arg-Lys-Asp-Val-Tyr-Arg Peptide (d) Tyr-Arg-Lys-Asp-Val-Tyr-Arg Peripheral blood lymphocytes (PBL) were purified by isopicnic centrifugation, washed and diluted in complete RPMI 1640 medium, supplemented with human AB sera. IO 5 cells were added into the wells of 96 well plates, which contain 100 μl of tested substances, diluted in RPMI 1640 culture medium as above, and a suboptimal amount of PHA. Cells were cultured for 4 days and 3 H-thymidine was added into each well for 24 hours. Cells were harvested and incorporation of 3 H-thymidine was measured by scintillation counting. All experiments were conducted in quadruplicate. The addition of peptides to the peripheral blood lymphocytes of patients with depressed immunity, as reflected by decreased expression of T-cell subset markers and lymphocyte deviations, normalizes these characteristics. Positive results were achieved within one hour of incubation, while no normalization was seen after such time when any presently known sequence was added. By contrast, previously known sequences led to limited normalization, but only after 18 - 24 hours of incubation. The experimental data of such comparative testing is set forth in Table 2. With respect to the data set forth in Table 2, the PBL of normal persons and patients were treated by the peptide Glu-Lys-Lys-Asp-Val-Tyr-Arg or Thymosin alpha-1 fragment N23-27 in culture medium for either 1 hour or 24 hours. Expression of CD4, CD8 and NK markers was detected by immunofluorescene as being the number of positive cells in cultures. All experiments were conducted in triplicate. P was calculated by using the t distribution of Student. As measured by 3 H-thymidine uptake, the peptides of the invention were able to restore normal response to phytohemagglutinin, while the amino acid sequences of peptides known to the prior art failed to do so. The experimental results are presented in Table 3. (Such comparative testing was performed in a manner similar to that described above for the test results set forth in Table 1. PBL of patients with signs of immunodeficiency were tested for PHA-induced 3 H-thymidine uptake in the presence of tested substances in culture medium. ) It is known that vaccinia virus partially protects the mouse from infection with Ectromelia virus. The latter infection is lethal in most cases in inbred mice. Mice BALB/c received peptides of the present invention in doses of from 0.1 meg to 1 meg per kg of body weight, one day prior to exposure to vaccinia virus. A month later, they were injected with Ectromelia virus in an extract from the spleen and liver of spontaneously infected animals. The clinical signs of infection on record were hepatosplenomegaly, mucosal inflammation and necrosis of extremities and tail. The potentiating effect of peptides following vaccination with viccinia virus was evident. The test results are presented in Table 4 for the peptide Tyr-Arg-Lys-Glu-Leu-Tyr-Arg versus a placebo. (In Table 4, P was calculated using the "F" distribution of Fischer, also known as Fischer's exact test. ) A single injection of a peptide one day prior to intranasal application in mice C57BL/6 with Influenza A virus strain WSN saved a significant number of animals. (See, Table 5.) The peptide had the amino acid sequence of Tyr-Arg-Lys-Glu-Leu-Glu-Lys-Lys-Glu. Mortality was recorded during a two-week period. P was calculated using the "F" distribution of Fischer. Peptides of the present invention, injected in doses of from 0.1 meg to 1 meg per kg of mouse body weight, normalized the depleted T-cell immunity of thymectomized animals. In toxicity studies, no toxicity was observed for the peptides of the invention in doses of up to 1 g per kg of mouse body weight; 20 subcutaneous or intraperitoneal injections every other day of the same dose also failed to produce any signs of toxicity. There were no significant changes in arterial blood pressure, heart rate, respiration or body temperature between the placebo group and animals injected with peptides during acute or chronic toxicity studies. The peptides of the invention did not cause any morphological changes in the brain, heart, lung, kidney and liver tissues. Complete blood counts on the experimental animals revealed an elevation of white blood cells to high normal levels. Hyperplasia of the thymus and thymus- dependent zones of lymph nodes was recorded. The medical formulations of the present invention preferably include an effective amount of one or more peptides and a solubilizer, with the possible inclusion of additional carriers and preservatives, as determined by the specifics of the different product formulations so desired by the skilled artisan. Solubilizers useful in combination with the peptides of the present invention include any solubilizer which is compatible with bodily fluids. Examples of solubilizers are water, solvents such as dimethylsulfoxide, propylene glycol, dimethylform- a ide and mixtures thereof, and surface active agents, such as non-ionic alkylene oxide block copolymers. When the solubilizer used is water, additional additives can be used to achieve physiological concentrations of inorganic salts, normal osmotic pressure and effective lyophilization. Such additives can be selected from, for example, sodium chloride and potassium chloride, sodium and potassium phosphate salts, sucrose, glucose, protein hydro- lysate, dextran, polyvinylpyrrolidone and poly¬ ethylene glycol, among others. In accordance with a preferred embodiment, peptides are included in medical treatment composition of the present invention in- order to provide doses ranging from 0.0001 mg to about 5 mg per kg of body weight for parenteral use, as well as concentrations ranging from about 0.0001% to about 5% for topical use. A preferred composition of the present invention for parenteral usage is a 0.01% solution of peptides in 1 ml of 0.85 wt-% sodium chloride containing 0.1 wt-% of ascorbic acid; it can be lyophilized in the presence of 100 mg glucose. A preferred composition of the present invention for eye and ear drops, for example, is a composition comprising a 0.0001 wt-% solution of peptides in a 0.85% sodium chloride solution. The medicinal compositions utilizing the peptides of the present invention may be used for immunomodulation of various immunodeficiencies and immunosuppressed conditions, T-cell subset and lymphocyte deviations, enhancement of a vaccine's efficacy, as well as for immunotherapy, including infections, local or systemic complications of non- infectious diseases, postoperatives inflammations, wounds and burns. While only several embodiments of the present invention have been described, it will be obvious to those of ordinary skill in the art that many modifications may be made to the present invention without departing from the spirit and scope thereof.

Claims: Claims 1. A peptide compound, or an acid or base salt thereof, constructed by combination and/or overlap¬ ping of the amino acid sequences: AiBi X B2A2 , A3B3 X A 4 B 4 , BsAs X AβBe , B7A7 X BeAs , A9B9 , Ai0Al1 , B10A12 and/or Bi 1 Bi2 , wherein, X is a hydrophobic or neutral amino acid independently selected from the group consisting of Ala, D-Ala, Gly, D-Gly, Ile, D-Ile, Leu, D-Leu, Met, D-Met, Phe, D-Phe , Pro, D-Pro, Sar, D-Sar, Ser, D-Ser, Tre, D-Tre, Trp, D-Trp, Val and D-Val; Ai through A12 are, independently, neutral or positively-side-chain-charged amino acids independently selected from the group consisting of Ala, D-Ala, Arg, D-Ar , Asp, D-Asp, Glu, D-Glu, Gly, D-Gly, His, D-His, Ile, D-Ile, Leu, D-Leu, Met, D-Met, Phe, D-Phe , Pro >3 D-Pro, dehydro Pro, Sar, D-Sar, Ser, D-Ser, Tre, D-Tre, -32- Trp , D-Trp, Val and 2>-Val ; and, Bi through B12 are, independently, neutral or negatively-side-chain-charged amino acids independently selected from the group consisting of Ala, D-Ala, Asp, D-Asp, Glu, D-Glu, Gly, D-Gly, Ile, D-Ile, Leu, D-Leu, Met, D-Met. Phe, D-Phe, Pro, D-Pro, dehydro Pro, Sar, D-Sar, Tre, D-Tre, Tyr, D-Tyr, Val, D-Val, L-2- amino- glutaryl, D-2-amino lutaryl, -2-aminoadiphyl, D-2-aminoadiphyl, -2-aminopimelyl and D-2-aminopimelyl. 2. The peptide compound according to Claim 1, wherein, X is an amino acid selected from the group consisting of Ala, Gly, Ile, Leu, Phe and Val; Ai through An are amino acids independently selected from the group consisting of Arg, Asn, Gin, Lys, Phe and Val; and, i through Bn are amino acids independently selected from the group consisting, of Asp, Glu, Tyr, Phe and Val. 3. The peptide compound according to Claim 1, wherein said peptide compound has balanced side chain charges of amino acid sequences which are symmetrical to X. 4. The peptide compound according to Claim 1, wherein said peptide compound has uncompensated opposite side chain charges of amino acid sequences relative to X. 5. The peptide compound according to Claim 1, wherein said peptide compound is Glu-Arg-Lys-Glu-Leu- Tyr-Arg. 6. The peptide compound according to Claim 1, wherein said peptide compound is Tyr-Arg-Lys-Asp-Val- Tyr-Arg. 7. The peptide compound according to Claim 1, wherein said peptide compound is Tyr-Arg-Lys-Glu-Leu- Tyr-Ar . 8. The peptide compound according to Claim 1, wherein said peptide compound is Glu-Arg-Lys-Asp-Val- Tyr-Ar . 9. The peptide compound according to Claim 1 , wherein said peptide compound is a member selected from the group consisting of : Arg-Asp-Lys-Asp-Val -Tyr-Arg; Lys-Asp-Lys-Asp-Val-Tyr-Lys; Lys-Glu-Lys-Asp-Val-Tyr-Lys; Arg-Glu-Arg-Asp-Val -Tyr-Arg; Lys-Glu-Leu-Tyr-Arg -Lys-Glu; Lys-Glu-Leu-Glu-Lys ■ Lys-Glu; Arg-Glu-Leu-Glu-Arg • Arg-Glu; Lys-Asp-Val-Asp-Lys ■ Lys-Asp; Lys-Asp-Leu-Glu-Lys •Lys-Glu; Tyr-Arg-Lys-Asp-Val- Tyr-Arg-Lys-Glu; Tyr-Arg-Lys-Glu-Leu- Glu-Lys-Lys-Glu; Glu-Lys-Lys-Glu-Leu- Tyr-Arg-Lys-Glu; Tyr-Arg-Lys-Glu-Leu- Tyr-Arg-Glu-Lys; Tyr-Arg-Lys-Asp-Val- Tyr-Arg-Lys-Asp-Val-Tyr-Arg; Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Lys-Glu-Leu-Tyr-Arg; Glu-Arg-Lys-Glu-Leu-Tyr-Arg-Lys-Glu-Leu-Tyr-Ar ; ■ Tyr-Arg-Lys-Asp-Val- -Tyr-Arg-Lys-Glu-Val- ■ Glu-Arg-Lys-Glu-Val- -Glu-Lys-Lys-Glu-Leu- -Glu-Lys-Lys-Asp-Leu- •Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Lys-Asp-Val- ■ Tyr-Lys-Lys-Glu-Leu-Tyr-Arg-Lys-Glu-Leu- -Tyr-Arg-Lys-Glu-Leu-Tyr-Arg-Lys-Glu-Leu- -Tyr-Arg-Lys-Asp-Val-Tyr-Arg-Lys-Asp-Val- and, r" "' ■ Glu-Lys-Lys-Glu-Leu-Glu-Lys-Lys-Glu-Leu- 10. The peptide compound according to Claim 1, wherein said peptide compound is a member selected from the group consisting of: Arg-Lys-Asp-Val-Lys-Tyr; Arg-Lys-Asp-Val-Arg-Tyr; Arg-Lys-Asp-Val-Phe-Glu; Arg-Glu-Glu-Val-Phe-Glu; Arg-Lys-Asp-Val-Tyr-Arg ; Arg-Asn- Asp-Val-Tyr- Ar ; Arg-Lys-Glu-Leu-Tyr-Arg ; Arg-Gln-Glu-Leu-Tyr-Arg ; Arg-Lys-Asp-Val-Tyr-Lys ; Arg-Asn-Asp-Val-Tyr-Lys ; Arg-Lys-Glu-Leu-Tyr-Lys ; Arg-Gln-Glu-Leu-Tyr-Lys ; Arg-Lys-Asp-Val -Glu-Ar ; Arg-Lys-Glu-Leu-Glu-Ar ; Arg-Lys-Glu-Val-Glu-Arg ; Arg-Phe-Leu-Tyr-Arg-Asp ; Phe-Tyr-Arg-Leu-Arg-Tyr ; Glu-Tyr-Arg-Leu-Arg-Tyr ; Glu-Tyr-Arg-Leu-Tyr-Ar ; Lys-Glu-Leu-Gln-Glu-Glu ; Lys-Asp-Val-Arg-Tyr-Tyr ; Lys-Asp-Val-Lys-Phe-Glu ; Lys-Asp-Val-Arg-Phe-Glu ; Lys-Asp-Val-Arg-Tyr-Asp ; Arg-Tyr-Asn-Val-Tyr-Ar ; Arg-Tyr-Gln-Leu-Tyr-Arg ; Arg-Tyr-Asn-Val-Tyr-Lys ; Arg-Tyr-Gln-Leu-Tyr-Lys ; Arg-Glu-Lys-Leu-Tyr-Ar ; Gln-Glu-Lys-Leu-Tyr-Arg ; Gln-Asp-Lys-Leu-Tyr-Arg ; Asn-Asp-Lys-Leu-Tyr-Ar ; Lys-Tyr-Val-Tyr-Arg-Asp ; Tyr-Arg-Asp-Val-Tyr-Ar ; Tyr-Lys-Asp-Val-Tyr-Lys ; Tyr-Lys-Glu-Leu-Tyr-Arg ; Asp-Asn-Tyr-Val-Tyr-Arg ; Asp-Asn-Tyr-Leu-Glu-Ar ; Asp-Asn-Tyr-Leu-Glu-Gln; Arg-Asn-Lys-Asp-Val-Tyr-Arg ; Arg-Gln-Arg-Glu-Leu-Tyr-Arg ; Arg-Asn-Arg-Tyr-Leu-Tyr-Ar ; Arg-Asp-Val-Tyr-Arg-Gln-Asn ; Lys-Asp-Val-Tyr-Arg-Gln-Asn; Arg-Asp-Val-Tyr-Lys-Gln-Asn ; Asp-Glu-Lys-Glu-Leu-Tyr-Arg ; 30 Glu-Glu -Lys-Asp-Val- Tyr-Arg Asp-Glu -Gln-Glu-Leu-•Phe-Arg Gin-Asp -Val-Tyr-Arg- Glu-Asp Gln-Glu -Asn-Asp-Val- Glu-Gln Asn-Asp -Gln-Glu-Leu- Glu-Gln 35 Asn-Asp -Lys-Asp-Val-Asp-Lys Gln-Glu -Asp-Lys-Leu-Tyr-Arg Arg-Glu -Asp-Lys-Leu- Tyr-Arg Arg-Glu -Asp-Arg-Leu- Tyr-Arg Arg-Asp -Glu-Arg-Leu- Tyr-Arg 40 Arg-Glu -Tyr-Arg-Leu-Tyr-Arg Lys-Glu -Tyr-Arg-Leu-Tyr-Arg Lys-Asp -Val-Tyr-Arg-Arg-Tyr Lys-Asp -Val-Tyr-Arg- Lys-Tyr Lys-Asp -Val-Tyr-Arg- Lys-Asp 45 Lys-Glu -Leu-Glu-Arg- Lys-Glu Arg-Asp -Val-Asp-Lys- Lys-Asp Lys-Asp -Leu-Glu-Lys- Lys-Asp Lys-Glu -Leu-Lys-Glu-Lys-Glu Lys-Asp -Leu-Lys-Glu- Lys-Asp 50 Glu-Arg -Lys-Asp-Val-Tyr-Arg Glu-Lys -Lys-Asp-Val-Tyr-Arg Asp-Arg -Lys-Asp-Val-Tyr-Arg Lys-Glu -Leu-Lys-Glu-Tyr-Arg Lys-Asp-Val-Lys-Glu-Tyr-Lys ; Glu-Lys-Lys-Glu-Leu-Glu-Lys-Lys-Glu; Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Arg-Tyr ; Glu-Lys-Lys-Glu-Leu-Arg-Tyr-Tyr-Arg ; Tyr-Arg-Lys-Asp-Val-Lys-Tyr-Tyr-Arg ; Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Tyr-Arg ; Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Glu-Arg ; Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Glu-Arg ; Glu-Lys-Lys-Glu-Leu-Glu-Gln-Tyr-Arg ; Glu-Lys-Lys-Glu-Leu-Glu-Gln-Asp-Asn; Lys-Glu-Glu-Lys-Leu-Glu-Lys-Lys-Glu ; Lys-Asp-Asp-Lys-Leu-Tyr-Arg-Gln-Glu ; Gln-Glu-Asp-Lys-Leu-Tyr-Arg-Gln-Glu; Gln-Glu-Asp-Lys-Leu-Tyr-Arg-Gln-Glu ; Arg-Tyr-Leu-Arg-Tyr-Leu-Tyr-Arg ; Arg-Tyr-Leu-Lys-Glu-Leu-Tyr-Arg ; Tyr-Arg-Gly-Lys-Glu-Leu-Tyr-Arg ; Arg-Tyr-Leu-Tyr-Arg-Lys-Asp-Val-Tyr-Arg ; and , Arg-Tyr-Leu-Glu-Lys-Lys-Glu-Leu-Tyr-Arg . 11. A composition having immuno heapeutic activity, comprising: a peptide compound, or an acid or "base salt thereof, constructed by combination and/or overlap- ping of the amino acid sequences : Ai Bi X B2 A2 , A3 B3 X A4 B , Bs As X Ae Be , B7 A7 X BS AB , A9 B9 , Ai o Ai i , B1 0 A1 2 and/or Bi 1 Bi 2 , wherein , X is a hydrophobic or neutral amino acid independently selected from the group consisting of Ala, D-Ala, Gly, D-Gly, Ile, D-Ile, Leu, D-Leu, Met, D-Met, Phe, D-Phe, Pro, D-Pro, Sar, D-Sar, Ser, D-Ser, Tre, D-Tre, Trp, D-Trp, Val and D-Val; Ai through Ai2 are, independently, neutral or positively-side-chain-charged amino acids independently selected from the group consisting of Ala, D-Ala, Arg, D-Arg, Asp, D- Asp, Glu, D-Glu, Gly, D-Gly, His, D-His, Ile, D-Ile, Leu, D-Leu, Met, D-Met, Phe, D-Phe, Pro, D-Pro, dehydro Pro, Sar, D-Sar, Ser, D-Ser, Tre, D-Tre, Trp, D-Trp, Val and D-Val; and, Bi through B12 are, independently, neutral or negatively-side-chain-charged amino acids independently selected from the group consisting of Ala, D-Ala, Asp, D-Asp, Glu, D-Glu, Gly, D-Gly, Ile, D-Ile, Leu, D-Leu, Met, D-Met. Phe, D-Phe, Pro, D-Pro, dehydro Pro, Sar, D-Sar, Tre, D-Tre, Tyr, D-Tyr, Val, D-Val, L-2- a ino- glutaryl, D-2-aminoglutaryl, -2-aminoadiphyl, D-2-aminoadiphyl, X-2-aminopimelyl and D-2-aminopimelyl; and, a solubilizer for said peptide compound. 12. The composition having immunotherapeutic activity according to Claim 11, wherein said peptide compound is Glu-Arg-Lys-Glu-Leu-Tyr-Arg. 13. The composition having immunotherapeutic activity according to Claim 11, wherein said peptide compound is Tyr-Arg-Lys-Asp-Val-Tyr-Arg. 14. The composition having immunotherapeutic activity according to Claim 11, wherein said peptide compound is Tyr-Arg-Lys-Glu-Leu-Tyr-Arg. 15. The composition having immunotherapeutic activity according to Claim 11, wherein said peptide compound is Glu-Arg-Lys-Asp-Val-Tyr-Arg. 16. The composition having immunotherapeutic activity according to Claim 11, wherein said peptide compound is a member selected from the group consisting of: Arg-Asp-Lys-Asp-Val-Tyr-Arg; Lys-Asp-Lys-Asp-Val-Tyr-Lys; Lys-Glu-Lys-Asp-Val-Tyr-Lys; Arg-Glu-Arg-Asp-Val-Tyr-Arg; Lys-Glu-Leu-Tyr-Arg-Lys-Glu; Lys-Glu-Leu-Glu-Lys-Lys-Glu; Arg-Glu-Leu-Glu-Arg-Arg-Glu; Lys-Asp-Val-Asp-Lys-Lys-Asp; Lys-Asp-Leu-Glu-Lys-Lys-Glu; Tyr-Arg-Lys-Asp-Val-Tyr-Arg-Lys-Glu; Tyr-Arg-Lys-Glu-Leu-Glu-Lys-Lys-Glu; Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Lys-Glu; Tyr-Arg-Lys-Glu-Leu-Tyr-Arg-Glu-Lys; Tyr-Arg-Lys-Asp-Val-Tyr-Arg-Lys-Asp-Val-Tyr-Arg; Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Lys-Glu-Leu-Tyr-Arg; Glu-Arg-Lys-Glu-Leu-Tyr-Arg-Lys-Glu-Leu-Tyr-Arg ; -Tyr-Arg-Lys-Asp-Val- -Tyr-Arg-Lys-Glu-Val- -Glu-Arg-Lys-Glu-Val- -Glu-Lys-Lys-Glu-Leu- -Glu-Lys-Lys-Asp-Leu- -Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Lys-Asp-Val- -Tyr-Lys-Lys-Glu-Leu-Tyr-Arg-Lys-Glu-Leu- 'Tyr-Arg-Lys-Glu-Leu-Tyr-Arg-Lys-Glu-Leu- -Tyr-Arg-Lys-Asp-Val-Tyr-Arg-Lys-Asp-Val- and , i ■ Glu-Lys-Lys-Glu-Leu-Glu-Lys-Lys-Glu-Leu- 17. The composition having immunotherapeutic activity according to Claim 11, wherein said peptide compound is a member selected from the group consisting of: Arg-Lys-Asp-Val-Lys-Tyr Arg-Lys-Asp-Val-Arg-Tyr; Arg-Lys-Asp-Val-Phe-Glu Arg-Glu-Glu-Val-Phe-Glu; Arg-Lys-Asp-Val-Tyr-Arg Arg-Asn-Asp-Val-Tyr-Ar ; Arg-Lys-Glu-Leu-Tyr-Arg Arg-Gln-Glu-Leu-Tyr-Arg Arg-Lys-Asp-Val-Tyr-Lys Arg-Asn-Asp-Val-Tyr-Lys; Arg-Lys-Glu-Leu-Tyr-Lys Arg-Gln-Glu-Leu-Tyr-Lys Arg-Lys-Asp-Val-Glu-Arg Arg-Lys-Glu-Leu-Glu-Arg; Arg-Lys-Glu-Val-Glu-Arg Arg-Phe-Leu-Tyr-Arg-Asp; Phe-Tyr-Arg-Leu-Arg-Tyr Glu-Tyr-Arg-Leu-Arg-Tyr; Glu-Tyr-Arg-Leu-Tyr-Arg Lys-Glu-Leu-Gln-Glu-Glu; Lys-Asp-Val-Arg-Tyr-Tyr Lys-Asp-Val-Lys-Phe-Glu; Lys-Asp-Val-Arg-Phe-Glu Lys-Asp-Val-Arg-Tyr-Asp; Arg-Tyr-Asn-Val-Tyr-Arg Arg-Tyr-Gln-Leu-Tyr-Arg; Arg-Tyr-Asn-Val-Tyr-Lys Arg-Tyr-Gln-Leu-Tyr-Lys; Arg-Glu-Lys-Leu-Tyr-Arg Gln-Glu-Lys-Leu-Tyr-Ar ; Gln-Asp-Lys-Leu-Tyr-Arg Asn-Asp-Lys-Leu-Tyr-Arg: Lys-Tyr-Val-Tyr-Arg-Asp Tyr-Arg-Asp-Val-Tyr-Arg; Tyr-Lys-Asp-Val-Tyr-Lys Tyr-Lys-Glu-Leu-Tyr-Arg: Asp-Asn-Tyr-Val-Tyr-Arg Asp-Asn-Tyr-Leu-Glu-Arg Asp-Asn-Tyr-Leu-Glu-Gln Arg-Asn-Lys-Asp-Val-Tyr-Arg; Arg-Gln-Arg-Glu -Leu-Tyr-Arg; Arg-Asn-Arg-Tyr-Leu-Tyr-Arg; Arg-Asp-Val-Tyr-Arg-Gln-Asn; Lys-Asp-Val-Tyr-Arg-Gln-As ; Arg-Asp-Val-Tyr-Lys-Gln-Asn; 30 Asp-Glu-Lys-Glu-Leu-Tyr-Arg; Glu-Glu-Lys-Asp-Val-Tyr-Arg; Asp-Glu-Gln-Glu-Leu-Phe-Arg; Gln-Asp-Val-Tyr-Arg-Glu-Asp; Gln-Glu-Asn-Asp-Val-Glu-Gl ; 35 Asn-Asp-Gln-Glu-Leu-Glu-Gln; Asn-Asp-Lys-Asp-Val-Asp-Lys; Gln-Glu-Asp-Lys-Leu-Tyr-Arg; Arg-Glu-Asp-Lys-Leu-Tyr-Arg; Arg-Glu-Asp-Arg-Leu-Tyr-Ar ; 40 Arg-Asp-Glu-Arg-Leu-Tyr-Ar ; Arg-Glu-Tyr-Arg-Leu-Tyr-Arg; Lys-Glu-Tyr-Arg-Leu-Tyr-Arg; Lys-Asp-Val-Tyr-Arg-Arg-Tyr; Lys-Asp-Val-Tyr-Arg-Lys-Tyr; 45 Lys-Asp-Val-Tyr-Arg-Lys-Asp; Lys-Glu-Leu-Glu-Arg-Lys-Glu; Arg-Asp-Val-Asp-Lys-Lys-Asp; Lys-Asp-Leu-Glu-Lys-Lys-Asp; Lys-Glu-Leu-Lys-Glu-Lys-Glu; 50 Lys-Asp-Leu-Lys-Glu-Lys-Asp ; Glu-Arg-Lys-Asp-Val-Tyr-Arg ; Glu-Lys-Lys-Asp-Val-Tyr-Ar ; Asp-Arg-Lys-Asp-Val-Tyr-Arg ; Lys-Glu-Leu-Lys-Glu-Tyr-Arg ; 55 Lys-Asp-Val-Lys-Glu-Tyr-Lys ; Glu-Lys-Lys-Glu-Leu-Glu-Lys-Lys-Glu ; Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Arg-Tyr ; Glu-Lys-Lys-Glu-Leu-Arg-Tyr-Tyr-Arg : Tyr-Arg-Lys-Asp-Val-Lys-Tyr-Tyr-Arg ; 60 Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Tyr-Arg : Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Glu-Arg ; Glu-Lys-Lys-Glu-Leu-Tyr-Arg-Glu-Arg Glu-Lys-Lys-Glu-Leu-Glu-Gln-Tyr-Arg ; Glu-Lys-Lys-Glu-Leu-Glu-Gln-Asp-Asn ; 65 Lys-Glu-Glu-Lys-Leu-Glu-Lys-Lys-Glu : Lys-Asp-Asp-Lys-Leu-Tyr-Arg-Gln-Glu ; Gln-Glu-Asp-Lys-Leu-Tyr-Arg-Gln-Glu ; Gln-Glu-Asp-Lys-Leu-Tyr-Arg-Gln-Glu ; Arg-Tyr-Leu-Arg-Tyr-Leu-Tyr-Arg ; 70 Arg-Tyr-Leu-Lys-Glu-Leu-Tyr-Arg ; Tyr-Arg-Gly-Lys-Glu-Leu-Tyr-Arg ; Arg-Tyr-Leu-Tyr-Arg-Lys-Asp-Val-Tyr-Arg ; and , Arg-Tyr-Leu-Glu-Lys-Lys-Glu-Leu-Tyr-Arg . 18. The composition having immunotherapeutic activity according to Claim 11, wherein said peptide compound is incorporated into a polymeric matrix selected from the group consisting of a polyanhydride copolymer, ethylen-vinyl acetate copolymer, lactic acid-glycolic acid copolymer, polyhydroxymethyl- metacrilate, polyvinyl alcohol and a combination thereof. 19. The composition having immunotherapeutic activity according to Claim 11, wherein said solubilizer is a member selected from the group consisting of water, dimethylsulfoxide, propylene glycol, dimethylformamide and a combination thereof. 20. The composition having immunotherapeutic activity according to Claim 11, wherein said solubilizer is a non-ionic alkylene oxide block copolymer. 21. The composition having immunotherapeutic activity according to Claim 11, further comprising an additive selected from the group consisting of a stabilizer, a viscosifier, a preservative and a combination thereof.

Inventors: ATKIN ANDREW, ATKIN, ANDREW
Applicants: IMMUNODYNAMICS INC, IMMUNODYNAMICS, INC.
Application year: 1991
Main classification: C07K7
IPC codes: A61K38, C07K7, C07K14