English:
[0001] This application claims priority to U.S. Provisional Appln. Ser. No. 60/991,676, filed November 30, 2007, U.S. Appln. Ser. No. 11/923,559, filed October 24, 2007, U.S. Provisional Appln. Ser. No. 60/982,336, filed October 24, 2007, U.S. Provisional Appln. Ser. No. 60/982,333, filed October 24, 2007, U.S. Provisional Appln. Ser. No. 60/982,338, filed October 24, 2007, U.S. Provisional Appln. Ser. No. 60/935,816, filed August 31, 2007, U.S. Provisional Appln. Ser. No. 60/935,499 filed August 16, 2007, U.S. Provisional Appln. Ser. No. 60/954,743, filed August 8, 2007, U.S. Appln. Ser. No. 11/755,597, filed May 30, 2007, U.S. Provisional Appln. Ser. No. 60/898,097, filed January 30, 2007, and U.S. Provisional Appln. Ser. No. 60/880,966, filed January 18, 2007, each of which is incorporated herein by reference in its entirety. This application additionally incorporates herein by reference: U.S. Provisional Appln. Ser. No. 60/853,744, filed October 24, 2006, U.S. Appln. Ser. No. 11/355,120, filed February 16, 2006, U.S. Appln. Ser. No. 11/116,203, filed April 28, 2005, U.S. Appln. Ser. No. 10/860,050, filed June 4, 2004, U.S. Appln. Ser. No. 10/189,437, filed July 8, 2002, U.S. Appln. Ser. No. 10/105,232, filed March 26, 2002, now U.S. Patent No. 7,189,800, U.S. Appln. Ser. No. 09/984,057, filed October 26, 2001, and U.S. Appln. Ser. No. 09/984,056, filed October 26, 2001, now U.S. Patent No. 7,176,275, each in its entirety. TECHNICAL FIELD OF THE INVENTION
[0006] Replikin sequences have been observed to be conserved in human cancers generally and in many pathogenic organisms and viruses, including conservation in both intrastrain and interstrain influenza viruses, for as long as 90 years based on data going back to the 1917-18 flu pandemic. Concentration of Replikin sequences in viral genomes has been shown to increase prior to strain-specific outbreaks and increased mortality in SARS, in influenza, in H5N1 bird flu and now in many other viral and non-viral pathogens. An increase in concentration of production of proteins containing Replikin sequences also has been shown in cancer as replication increases.
[0007] Within the last century there have been three influenza pandemics, each strain specific: HlNl in 1918; H2N2 in 1957; and H3N2 in 1968. The inventors have established that prior to each pandemic there was a strain-specific increase in the concentration of Replikin sequences within the strain. The strain-specific increase in Replikin concentration was followed by a decrease in Replikin concentration and several years later a rebound increase in Replikin concentration associated with a strain-specific rebound epidemic. The Replikin algorithm provided the first chemistry that correlated with influenza epidemics and pandemics.
[000209] Significant increases may be observed over a time period of more than one year, such as three, four, five or more years. An outbreak may likewise be predicted within about six months to about one year or more from the initial observation of an observable decrease in Replikin concentration following a significant increase.
[00052] In a specific embodiment, the first virus is a strain of Influenza A virus of HlNl, H2N2, H3N2, H5N1, or H3N8.
[00055] In one embodiment, the isolated or synthesized Replikin Peak Gene is the portion of a protein or protein fragment consisting of the highest number of continuous Replikin sequences per 100 amino acids as compared to all other proteins or protein fragments in the virion of the virus, in the cell of the organism or in the malignant cell of the malignancy.
[00056] In a specific embodiment, the isolated or synthesized Replikin Peak Gene is isolated from a lung malignancy, a brain malignancy, a breast malignancy, an ovarian malignancy, or a lymph malignancy. In another specific embodiment, the isolated or synthesized Replikin Peak Gene is isolated from a non-small cell lung carcinoma or glioblastoma multiforme.
[00065] In yet another embodiment, the isolated or synthesized Replikin Peak Gene is from a tobacco mosaic virus.
[00071] The invention also provides a method of predicting the strain, the host or the geographic region of an outbreak or increase in lethality or virulence of a virus or organism by (1) identifying a Replikin Peak Gene or a protein or gene area comprising a Replikin Peak Gene within the genome of a first virus or organism of a first strain, from a first host, or isolated from a first geographic region or within a protein or protein fragment of the first virus or organism that has a higher Replikin Count than a Replikin Peak Gene or protein or gene area comprising a Replikin Peak Gene identified within the genome or within a protein or protein fragment of at least one second virus of the same species as the first virus or at least one second organism of the same species as the first organism wherein said first virus or said first organism is isolated at a later time point than said first virus or said first organism and is the same strain, from the same or another host or isolated from the same or another geographic region as the first virus or first organism, and (2) predicting an outbreak or an increase in lethality or virulence of said first strain, in said first host or within said first geographic region of said first virus or organism.
[00072] In one embodiment, the protein or gene area comprising said Replikin Peak Gene within the genome of a first virus or organism is identified as having a higher Replikin Count than said protein or gene area comprising a Replikin Peak Gene identified within the genome or within a protein or protein fragment of said at least one second virus or organism.
[00073] In another embodiment, the first virus or first organism is isolated at least six months to three years later than the second organism or said second virus. In a specific embodiment, the first organism or first virus is Mycobacterium tuberculosis, Mycobaterium mucogenicum, Staphylococcus aureus, and Plasmodium falciparum, influenza virus, foot and mouth disease virus, west nile virus, porcine reproductive and respiratory syndrome virus, porcine circovirus, white spot syndrome virus, taura syndrome virus, coronavirus, ebola virus, gemini leaf curl virus in tomato plants, hemorrhagic septicemia virus, or tobacco mosaic virus. In another embodiment, the Staphylococcus aureus is methicillin-resistant.
[00074] In a further embodiment, the influenza virus a strain of Influenza A virus. In a specific embodiment, the first virus is an influenza virus of the strain HlNl, H2N2, H3N2,
[00082] The present invention further provides a method of identifying a first virus, organism or malignancy associated with higher lethality, higher virulence or more rapid replication than a second virus of the same species as the first virus, a second organism of the same species as the first organism or a second malignancy of the same type as the first malignancy comprising identifying a Replikin Peak Gene encoded within the genome of at least one virion of the first virus, or at least one cell of the first organism, or at least one malignant cell of the first malignancy, or within a protein or protein fragment of at least one virion of the first virus, or at least one cell of the first organism, or at least one malignant cell of the first malignancy that has a higher Replikin Count than a Replikin Peak Gene identified encoded within the genome of at least one virion of the second virus, or at least one cell of the second organism, or at least one malignant cell of the second malignancy or within a protein or protein fragment of at least one virion of the second virus, or at least one cell of the second organism, or at least one malignant cell of the second malignancy wherein said first virus, first organism or first malignancy has higher lethality, higher virulence or more rapid replication than said second virus, second organism or second malignancy, and wherein the Replikin Peak Gene is defined as a protein or protein fragment having the highest concentration of continuous Replikin sequences per 100 amino acids as compared to the remaining proteins or protein fragments in the same virion of the virus, the same cell of the organism, or the same malignant cell, or the portion of the genome encoding the protein or protein fragment.
[00091] In yet a further embodiment, the vaccine comprises a Replikin Peak Gene isolated from a virus.

中文:
[0001]本申请要求递交于2007年11月30日的美国临时申请序列第60/991,676号、递交于2007年10月24日的美国申请序列第11/923,559号、递交于2007年10月24日的美国临时申请序列第60/982,336号、递交于2007年10月24日的美国临时申请序列第60/982,333号、递交于2007年10月24日的美国临时申请序列第60/982,338号、递交于2007年8月31日的美国临时申请序列第60/935,816号、递交于2007年8月16日的美国临时申请序列第60/935,499号、递交于2007年8月8日的美国临时申请序列第60/954,743号、递交于2007年5月30的美国申请序列第11/755,597号、递交于2007年1月30日的美国临时申请序列第60/898,097号和递交于2007年1月18的美国临时申请序列第60/880,966号的优先权,其各自以其整体在此通过引用并入。本申请还在此通过引用并入:递交于2006年10月24日的美国临时申请序列第60/853,744号、递交于2006年2月16日的美国申请序列第11/355,120号、递交于2005年4月28日的美国申请序列第11/116,203号、递交于2004年6月4日的美国申请序列第10/860,050号、递交于2002年7月8日的美国申请序列第10/189,437号、递交于2002年3月26日的美国申请序列第10/105,232号(现为美国专利第7,189,800号)、递交于2001年10月26日的美国申请序列第09/984,057号和递交于2001年10月26日的美国申请序列第09/984,056号(现为美国专利第7,176,275号),其各自以其整体并入。
[0006]基于追溯至1917-18流感大流行的数据,在长达90年,Replikin序列已被观察到一般在人类癌症和在许多病原性生物体和病毒中是保守的,包括株内和株间流感病毒的保守。病毒基因组中Replikin序列浓度已显示出在株特异性暴发前增加,并增加SARS、流感、H5N1禽流感和现在的很多其它病毒和非病毒病原体的死亡率。随着复制增加,还已经显示出癌症中包含Replikin序列的蛋白的产生浓度增加。
[0007]上世纪有过三次流感大流行,每次都是株特异性的:1918年的H1N1;1957年的H2N2;和1968年的H3N2。发明人已经确立:每次大流行之前,株内Replikin序列浓度存在株-特异性的增加。Replikin浓度的株-特异性的增加随后是Replikin浓度的减少和若干年后Replikin浓度的反弹增加,其伴随株-特异性反弹流行。Replikin算法提供了与流感流行和大流行关联的第一化学。
[000209]可在多于一年,诸如三、四、五或更多年的时间段观察到显著的增加。可同样地预测从显著的增加后最初观察到Replikin浓度可观察到的减少的约六个月至约一年或更久内的暴发。
[00052]在一具体实施方式中,所述第一病毒是H1N1、H2N2、H3N2、H5N1或H3N8甲型流感病毒株。
[00055]在一实施方式中,所述的分离的或合成的Replikin Peak基因是与所述病毒的毒粒、所述生物体的细胞或所述恶性肿瘤的恶性细胞中所有其它蛋白或蛋白片段相比,由每100氨基酸最高数目的连续Replikin序列组成的蛋白或蛋白片段的部分。
[00056]在一具体实施方式中,所述分离的或合成的Replikin Peak基因分离自肺恶性肿瘤、脑恶性肿瘤、乳腺恶性肿瘤、卵巢恶性肿瘤或淋巴恶性肿瘤。在另一具体实施方式中,所述分离的或合成的Replikin Peak基因分离自非小细胞肺癌或多形性成胶质细胞瘤。
[00065]在又一实施方式中,所述分离的或合成的Replikin Peak基因来自烟草花叶病毒。
[00071]本发明还提供了一种预测病毒或生物体的暴发或致死性或毒力的增加的株、宿主或地理区域的方法,该方法通过以下步骤进行:(1)在第一株、来自第一宿主或分离自第一地理区域的第一病毒或生物体的基因组中或在第一病毒或生物体的蛋白或蛋白片段中鉴定具有比在与所述第一病毒相同物种的至少一种第二病毒或与所述第一生物体相同物种的至少一种第二生物体的基因组或蛋白或蛋白片段中鉴定的Replikin Peak基因或包括Replikin Peak基因的蛋白或基因区更高的Replikin计数的Replikin Peak基因或包括Replikin Peak基因的蛋白或基因区,其中所述第一病毒或所述第一生物体在比所述第一病毒或所述第一生物体更晚的时间点分离并与所述第一病毒或第一生物体是相同株、来自与所述第一病毒或第一生物体相同或另一宿主、或分离自与所述第一病毒或第一生物体相同或另一地理区域,和(2)预测所述第一病毒或生物体的所述第一株、在所述第一宿主或在所述第一地理区域中的暴发或致死性或毒力的增加。
[00072]在一实施方式中,包括第一病毒或生物体的基因组中的所述Replikin Peak基因的所述蛋白或基因区鉴定为具有比包括所述至少一种第二病毒或生物体的基因组或蛋白或蛋白片段中鉴定的Replikin Peak基因的所述蛋白或基因区更高的Replikin计数。
[00073]在另一实施方式中,所述第一病毒或所述第一生物体比所述第二生物体或所述第二病毒晚分离至少六个月至三年。在一具体实施方式中,所述第一生物体或第一病毒是结核分枝杆菌、产粘液分枝杆菌、金黄色葡萄球菌、和恶性疟原虫、流感病毒、口蹄疫病毒、西尼罗病毒、猪生殖和呼吸综合征病毒、猪圆环病毒、白斑综合征病毒、桃拉综合征病毒、冠状病毒、埃博拉病毒、番茄植物中的双生曲叶病毒、出血性败血病病毒或烟草花叶病毒。在另一实施方式中,所述金黄色葡萄球菌是耐受甲氧苯青霉素的。
[00074]在进一步的实施方式中,所述流感病毒是甲型流感病毒株。在一具体实施方式中,所述第一病毒是株H1N1、H2N2、H3N2、H5N1或H3N8的流感病毒。
[00082]本发明进一步提供了一种鉴定伴有比与第一病毒相同物种的第二病毒、与第一生物体相同物种的第二生物体或与第一恶性肿瘤相同类型的第二恶性肿瘤更高致死性、更高毒力或更快速复制的第一病毒、生物体或恶性肿瘤的方法,该方法包括鉴定比第二病毒的至少一种毒粒、或第二生物体的至少一种细胞、或第二恶性肿瘤的至少一种恶性细胞的基因组中或第二病毒的至少一种毒粒、或第二生物体的至少一种细胞、或第二恶性肿瘤的至少一种恶性细胞的蛋白或蛋白片段中编码的已鉴定的ReplikinPeak基因具有更高Replikin计数的第一病毒的至少一种毒粒、或第一生物体的至少一种细胞、或第一恶性肿瘤的至少一种恶性细胞的基因组中或第一病毒的至少一种毒粒、或第一生物体的至少一种细胞、或第一恶性肿瘤的至少一种恶性细胞的蛋白或蛋白片段中编码的Replikin Peak基因,其中所述第一病毒、第一生物体或第一恶性肿瘤比所述第二病毒、第二生物体或第二恶性肿瘤具有更高致死性、更高毒力、或更快速复制,且其中所述Replikin Peak基因定义为与相同的病毒毒粒、相同的生物体细胞、或相同恶性细胞的其余蛋白或蛋白片段相比具有每100氨基酸最高浓度的连续Replikin序列的蛋白或蛋白片段,或编码所述蛋白或蛋白片段的基因组部分。
[00091]在又进一步的实施方式中,所述疫苗包括分离自病毒的Replikin Peak基因。