Method of reducing the harmful effects of orally or transdermally delivered nicotine

Abstract

The present invention generally relates to the reduction of the harmful effects of orally or transdermally delivered nicotine in conventional tobacco-use cessation programs. More specifically, embodiments concern methods of reducing the harmful effects of nicotine intake, associated with conventional tobacco-use cessation programs, by providing tobacco products, which contain a reduced amount of nicotine and tobacco specific nitrosamines (TSNAs).

1 - 34 . (canceled)  
     
     
         35 . A method of making a tobacco use cessation kit comprising: 
 providing a first tobacco product that comprises a tobacco produced from a genetically modified tobacco plant comprising a reduced level of an enzyme involved in nicotine biosynthesis, as compared to an unmodified tobacco plant of the same variety;    providing at least one additional tobacco product that comprises a tobacco produced from a genetically modified tobacco plant comprising a reduced level of an enzyme involved in nicotine biosynthesis, as compared to an unmodified tobacco plant of the same variety, wherein said subsequent tobacco products provide sequentially reduced amounts of nicotine, starting with a second product that provides less nicotine than said first tobacco product; and    incorporating said first tobacco product and said at least one additional tobacco product into said tobacco use cessation kit.    
     
     
         36 . The method of  claim 35 , wherein said enzyme involved in nicotine biosynthesis is selected from the group consisting of quinolate phosphoribosyl transferase (QPTase), putrescine N-methyltransferase (PMTase), N-methylputrescine oxidase, ornithine decarboxylase, S-adenosylmethionine synthetase, NADH dehydrogenase and phosphoribosylanthranilate isomerase.  
     
     
         37 . The method of  claim 35 , wherein said enzyme involved in nicotine biosynthesis is QPTase.  
     
     
         38 . The method of  claim 35 , wherein said enzyme involved in nicotine biosynthesis is PMTase.  
     
     
         39 . The method of  claim 35 , wherein said first tobacco product or said at least one additional tobacco product comprises a tobacco that comprises a portion of a DNA sequence that encodes an enzyme in the nicotine synthesis pathway or the complement thereof, wherein said portion of a DNA sequence is at least 25 nucleotides in length.  
     
     
         40 . The method of  claim 35 , wherein said first tobacco product or said at least one additional tobacco product comprises a tobacco that comprises a portion of a DNA sequence that encodes an enzyme in the nicotine synthesis pathway or the complement thereof, wherein said portion of a DNA sequence is at least 50 nucleotides in length.  
     
     
         41 . The method of  claim 35 , wherein said first tobacco product or said at least one additional tobacco product comprises a tobacco that comprises a DNA sequence that encodes an enzyme in the nicotine synthesis pathway or the complement thereof, wherein said portion of a DNA sequence is at least 100 nucleotides in length.  
     
     
         42 . The method of  claim 35 , wherein said first tobacco product or said at least one additional tobacco product comprises a tobacco that comprises a DNA sequence that encodes an enzyme in the nicotine synthesis pathway or the complement thereof, wherein said portion of a DNA sequence is at least 250 nucleotides in length.  
     
     
         43 . The method of  claim 35 , wherein said tobacco use cessation kit comprises a first tobacco product, a second tobacco product and a third tobacco product, wherein said second tobacco product provides less nicotine than said first tobacco product and said third tobacco product provides less nicotine than said first tobacco product and second tobacco product.  
     
     
         44 . The method of  claim 43 , wherein said first tobacco product provides 0.6 mg of nicotine, said second tobacco product provides 0.3 mg nicotine and said third tobacco product provides less than 0.05 mg nicotine.  
     
     
         45 . The method of  claim 35 , wherein said kit comprises a plurality of cigarette packages.  
     
     
         46 . The method of  claim 45 , wherein said cigarette packages are labeled to indicate the amount of nicotine present.  
     
     
         47 . A method of making a reduced risk tobacco use cessation kit comprising: 
 providing a first tobacco product that comprises a genetically modified tobacco that comprises a reduced level of an enzyme involved in nicotine biosynthesis, as compared to an unmodified tobacco plant of the same variety;    providing at least one additional tobacco product comprising a genetically modified tobacco that comprises a reduced level of an enzyme involved in nicotine biosynthesis, as compared to an unmodified tobacco plant of the same variety, wherein said subsequent tobacco products provide an amount of nicotine and a TSNA that are sequentially reduced, starting with a second product that provides an amount of nicotine and a TSNA that are less than the amount of nicotine and said TSNA in said first tobacco product; and    incorporating said first tobacco product and said at least one additional tobacco product into said reduced risk tobacco use cessation kit.    
     
     
         48 . The method of  claim 47 , wherein said enzyme involved in nicotine biosynthesis is selected from the group consisting of quinolate phosphoribosyl transferase (QPTase), putrescine N-methyltransferase (PMTase), N-methylputrescine oxidase, ornithine decarboxylase, S-adenosylmethionine synthetase, NADH dehydrogenase and phosphoribosylanthranilate isomerase.  
     
     
         49 . The method of  claim 47 , wherein said enzyme involved in nicotine biosynthesis is QPTase.  
     
     
         50 . The method of  claim 47 , wherein said enzyme involved in nicotine biosynthesis is PMTase.  
     
     
         51 . The method of  claim 47 , wherein said first tobacco product or said at least one additional tobacco product comprises a tobacco that comprises a portion of a DNA sequence that encodes an enzyme in the nicotine synthesis pathway or the complement thereof, wherein said portion of a DNA sequence is at least 25 nucleotides in length.  
     
     
         52 . The method of  claim 47 , wherein said first tobacco product or said at least one additional tobacco product comprises a tobacco that comprises a portion of a DNA sequence that encodes an enzyme in the nicotine synthesis pathway or the complement thereof, wherein said portion of a DNA sequence is at least 50 nucleotides in length.  
     
     
         53 . The method of  claim 47 , wherein said first tobacco product or said at least one additional tobacco product comprises a tobacco that comprises a portion of a DNA sequence that encodes an enzyme in the nicotine synthesis pathway or the complement thereof, wherein said portion of a DNA sequence is at least 100 nucleotides in length.  
     
     
         54 . The method of  claim 47 , wherein said first tobacco product or said at least one additional tobacco product comprises a tobacco that comprises a portion of a DNA sequence that encodes an enzyme in the nicotine synthesis pathway or the complement thereof, wherein said portion of a DNA sequence is at least 250 nucleotides in length.  
     
     
         55 . The method of  claim 47 , wherein said reduced risk tobacco use cessation kit comprises a first tobacco product, a second tobacco product and a third tobacco product, wherein said second tobacco product provides less nicotine and a TSNA than said first tobacco product and said third tobacco product provides less nicotine and said TSNA than said first tobacco product and second tobacco product.  
     
     
         56 . The method of  claim 55 , wherein said first tobacco product provides 0.6 mg of nicotine, said second tobacco product provides 0.3 mg nicotine and said third tobacco product provides less than 0.05 mg nicotine.  
     
     
         57 . The method of  claim 55 , wherein said first tobacco product provides less than 2 μg/g TSNA, said second tobacco product provides less than 1 μg/g TSNA, and said additional tobacco products provides less than 0.7 μg/g TSNA.  
     
     
         58 . The method of  claim 47 , wherein said kit comprises a plurality of cigarette packages.  
     
     
         59 . The method of  claim 58 , wherein said cigarette packages are labeled to indicate the amount of nicotine present.  
     
     
         60 . A method of reducing the nicotine consumption of a tobacco user comprising: 
 providing said tobacco user a first tobacco product that comprises a tobacco produced from a genetically modified tobacco plant comprising a reduced level of an enzyme involved in nicotine biosynthesis, as compared to an unmodified tobacco plant of the same variety; and    providing said tobacco user at least one additional tobacco product that comprises a tobacco produced from a genetically modified tobacco plant comprising a reduced level of an enzyme involved in nicotine biosynthesis, as compared to an unmodified tobacco plant of the same variety, wherein said subsequent tobacco products provide sequentially reduced amounts of nicotine, starting with a second product that provides less nicotine than said first tobacco product.    
     
     
         61 . The method of  claim 60 , wherein said enzyme involved in nicotine biosynthesis is selected from the group consisting of quinolate phosphoribosyl transferase (QPTase), putrescine N-methyltransferase (PMTase), N-methylputrescine oxidase, ornithine decarboxylase, S-adenosylmethionine synthetase, NADH dehydrogenase and phosphoribosylanthranilate isomerase.  
     
     
         62 . The method of  claim 61 , wherein said enzyme involved in nicotine biosynthesis is QPTase.  
     
     
         63 . The method of  claim 61 , wherein said enzyme involved in nicotine biosynthesis is PMTase.  
     
     
         64 . The method of  claim 60 , wherein said first tobacco product or said at least one additional tobacco product comprises a tobacco that comprises a portion of a DNA sequence that encodes an enzyme in the nicotine synthesis pathway or the complement thereof, wherein said portion of a DNA sequence is at least 25 nucleotides in length.  
     
     
         65 . The method of  claim 60 , wherein said method comprises a first tobacco product, a second tobacco product and a third tobacco product, wherein said second tobacco product provides less nicotine than said first tobacco product and said third tobacco product provides less nicotine than said first tobacco product and second tobacco product.  
     
     
         66 . The method of  claim 65 , wherein said first tobacco product provides 0.6 mg of nicotine, said second tobacco product provides 0.3 mg nicotine and said third tobacco product provides less than 0.05 mg nicotine.  
     
     
         67 . A method of reducing the TSNA consumption of a tobacco user comprising: 
 providing said tobacco user a first tobacco product that comprises a genetically modified tobacco that comprises a reduced level of an enzyme involved in nicotine biosynthesis, as compared to an unmodified tobacco plant of the same variety; and    providing said tobacco user at least one additional tobacco product comprising a genetically modified tobacco that comprises a reduced level of an enzyme involved in nicotine biosynthesis, as compared to an unmodified tobacco plant of the same variety, wherein said subsequent tobacco products provide an amount of a TSNA that is sequentially reduced, starting with a second product that provides an amount of a TSNA that is less than the amount of said TSNA in said first tobacco product.    
     
     
         68 . The method of  claim 67 , wherein said enzyme involved in nicotine biosynthesis is selected from the group consisting of quinolate phosphoribosyl transferase (QPTase), putrescine N-methyltransferase (PMTase), N-methylputrescine oxidase, ornithine decarboxylase, S-adenosylmethionine synthetase, NADH dehydrogenase and phosphoribosylanthranilate isomerase.  
     
     
         69 . The method of  claim 68 , wherein said enzyme involved in nicotine biosynthesis is QPTase.  
     
     
         70 . The method of  claim 68 , wherein said enzyme involved in nicotine biosynthesis is PMTase.  
     
     
         71 . The method of  claim 67 , wherein said first tobacco product or said at least one additional tobacco product comprises a tobacco that comprises a portion of a DNA sequence that encodes an enzyme in the nicotine synthesis pathway or the complement thereof, wherein said portion of a DNA sequence is at least 25 nucleotides in length.  
     
     
         72 . The method of  claim 67 , wherein said method comprises a first tobacco product, a second tobacco product and a third tobacco product, wherein said second tobacco product provides less nicotine and a TSNA than said first tobacco product and said third tobacco product provides less nicotine and said TSNA than said first tobacco product and second tobacco product.  
     
     
         73 . The method of  claim 72 , wherein said first tobacco product provides 0.6 mg of nicotine, said second tobacco product provides 0.3 mg nicotine and said third tobacco product provides less than 0.05 mg nicotine.  
     
     
         74 . The method of  claim 72 , wherein said first tobacco product provides less than 2 μg/g TSNA, said second tobacco product provides less than 1 μg/g TSNA, and said additional tobacco product provides less than 0.7 μg/g TSNA.