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US5749847A Expired / Lapsed US ⏱️ 0.0 years remaining

Delivery of nucleotides into organisms by electroporation

Assignee: Massachusetts Institute of Technology
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Filing: 1995-06-06
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Granted: 1998-05-12
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Expires: 2015-06-06
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Abstract

Abstract A method for delivering a nucleotide into an organism includes applying a composition which includes a nucleotide component to epidermis of the organism. The epidermis is electroporated, whereby at least a portion of the composition enters or passes across the epidermis, thereby delivering the nucleotide into the organism. An example of a suitable nucleotide which can be delivered by the method of the invention includes antisense oligodeoxynucleotides for treatment of melanomas.

Inventors

  • 👤 Thomas E. Zewert
  • 👤 Uwe Pliquett
  • 👤 Robert S. Langer
  • 👤 James C. Weaver

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-05 17:53
CPC Classifications
C; C12; C12N; C12N15/00; C12N15/09; C12N15/87; A; A61; A61B; A61B5/00; A61B5/145; A61B5/14507; A61B5/1451; A61B5/14514; A61K; A61K38/00; A61K38/16; A61K38/17; A61K38/38; A61K38/385; A61K38/43; A61K38/46; A61K38/48; A61K38/4873; A61K41/00; A61K41/0047; A61K48/00; A61N; A61N1/00; A61N1/18; A61N1/32; A61N1/325; A61N1/327; C07; C07K; C07K14/00; C07K14/82; A61B5/14532

Claims Analysis

Total Claims: 50
Claim 1
Independent Claim 68 words
A method for delivering a nucleotide component of a composition into an organism, comprising: a) applying the compositions which includes the nucleotide components to stratum corneum of the organism, whereby said nucleotide component directly contacts said stratum corneum; and thereafter b) electroporating the stratum corneum, whereby at least a portion of the composition enters or passes across the stratum corneum, thereby delivering the nucleotide component into the organism.
Claim 2
Independent Claim 68 words
A method for delivering a nucleotide component of a composition into an organism, comprising: a) applying the compositions which includes the nucleotide components to stratum corneum of the organism, whereby said nucleotide component directly contacts said stratum corneum; and thereafter b) electroporating the stratum corneum, whereby at least a portion of the composition enters or passes across the stratum corneum, thereby delivering the nucleotide component into the organism.
Claim 3
Dependent Claim 11 words
The method of claim 1 wherein the nucleotide is a polynucleotide.
Claim 4
Dependent Claim 11 words
The method of claim 1 wherein the nucleotide is an oligonucleotide.
Claim 5
Dependent Claim 11 words
The method of claim 1 wherein the nucleotide is a deoxyribonucleotide.
Claim 6
Dependent Claim 11 words
The method of claim 4 wherein the deoxynucleotide is an oligodeoxyribonucleotide.
Claim 7
Dependent Claim 11 words
The method of claim 1 wherein the nucleotide is a deoxynucleotide.
Claim 8
Dependent Claim 11 words
The method of claim 6 wherein the deoxynucleotide is an oligodeoxynucleotide.
Claim 9
Dependent Claim 12 words
The method of claim 7 wherein the oligodeoxynucleotide is an antisense oligodeoxynucleotide.
Claim 10
Dependent Claim 23 words
The method of claim 8 wherein the antisense oligodeoxynucleotide corresponds to at least a portion of a codon sequence in a c-myc gene.
Claim 11
Dependent Claim 22 words
The method of claim 9 wherein the antisense oligodeoxynucleotide is a 15-mer having a nucleotide sequence of 5'-AACGTTGAGGGGCAT-3' (SEQ. ID NO. 1).
Claim 12
Dependent Claim 18 words
The method of claim 10 wherein the c-myc antisense oligodeoxynucleotide corresponds to codons 1-5 of the c-myc gene.
Claim 13
Dependent Claim 23 words
The method of claim 8 wherein the antisense oligodeoxynucleotide corresponds to at least a portion of a codon sequence in a c-myb gene.
Claim 14
Dependent Claim 22 words
The method of claim 12 wherein the antisense oligodeoxynucleotide is a 24-mer having a nucleotide sequence of 5'-TATGCTGTGCCGGGGTCTTCGGGC-3' (SEQ. ID NO. 2).
Claim 15
Dependent Claim 18 words
The method of claim 13 wherein the c-myb antisense oligodeoxynucleotide corresponds to codons 2-9 of the c-myc gene.
Claim 16
Dependent Claim 21 words
The method of claim 1 wherein the epidermis is electroporated by applying a transdermal voltage of at least about 80 volts.
Claim 17
Dependent Claim 17 words
The method of claim 15 wherein the transdermal voltage is achieved by applying a series of pulses.
Claim 18
Dependent Claim 29 words
The method of claim 16 wherein the pulsed applied transdermal voltage has an average duration in a range of between about 0.5 milliseconds and about 50 milliseconds per pulse.
Claim 19
Dependent Claim 17 words
The method of claim 1 wherein at least a portion of the composition enters the stratum corneum.
Claim 20
Dependent Claim 27 words
The method of claim 1 wherein the composition passes across the stratum corneum from a first side of said epidermis to a second side of said epidermis.
Claim 21
Dependent Claim 11 words
The method of claim 1 wherein said composition includes a vaccine.
Claim 22
Dependent Claim 14 words
The method of claim 20 wherein said vaccine includes a plasmid deoxyribonucleic acid component.
Claim 23
Dependent Claim 28 words
The method of claim 1 further including the step of applying a polyanion to the stratum corneum prior to electroporating said stratum corneum, thereby inhibiting non-specific DNA binding.
Claim 24
Dependent Claim 11 words
The method of claim 22 wherein said polyanion includes an albumin.
Claim 25
Dependent Claim 12 words
The method of claim 23 wherein said albumin includes bovine serum albumin.
Claim 26
Dependent Claim 10 words
The method of claim 22 wherein said polyanion includes ficol.
Claim 27
Dependent Claim 12 words
The method of claim 1 wherein the composition includes a deoxyribonucleotide analog.
Claim 28
Dependent Claim 10 words
The method of claim 26 wherein said deoxyribonucleotide includes azidodeoxythymidine.
Claim 29
Dependent Claim 10 words
The method of claim 26 wherein said deoxyribonucleotide includes dideoxyinosine.
Claim 30
Dependent Claim 10 words
The method of claim 26 wherein said deoxyribonucleotide includes dideoxycytosine.
Claim 31
Dependent Claim 10 words
The method of claim 26 wherein said deoxyribonucleotide includes gancyclovir.
Claim 32
Dependent Claim 11 words
The method of claim 26 wherein said deoxyribonucleotide includes acyclovir vidarabine.
Claim 33
Dependent Claim 10 words
The method of claim 26 wherein said deoxyribonucleotide includes acyclovir.
Claim 34
Dependent Claim 10 words
The method of claim 26 wherein said deoxyribonucleotide includes ribavirin.
Claim 35
Dependent Claim 16 words
The method of claim 1 wherein the composition includes a label attached to said nucleotide component.
Claim 36
Dependent Claim 12 words
The method of claim 34 wherein said label is a radioactive label.
Claim 37
Dependent Claim 12 words
The method of claim 1 wherein the composition includes a Psoralin C2.
Claim 38
Dependent Claim 12 words
The method of claim 1 wherein the composition includes a phosphoramidate linkage.
Claim 39
Dependent Claim 11 words
The method of claim 37 wherein said phosphoramidate linkage includes butylamidate.
Claim 40
Dependent Claim 11 words
The method of claim 37 wherein said phosphoramidate linkage includes piperazidate.
Claim 41
Dependent Claim 11 words
The method of claim 37 wherein said phosphoramidate linkage includes morpholidate.
Claim 42
Dependent Claim 12 words
The method of claim 1 wherein the composition includes a phosphothioate linkage.
Claim 43
Dependent Claim 11 words
The method of claim 1 wherein the composition includes ribonucleic acid.
Claim 44
Dependent Claim 22 words
The method of claim 1 further including the step of applying a proteinase to said stratus corneum prior to electroporating said epidermis.
Claim 45
Dependent Claim 10 words
The method of claim 43 wherein said proteinase includes keratinase.
Claim 46
Dependent Claim 10 words
The method of claim 43 wherein said proteinase includes papain.
Claim 47
Dependent Claim 25 words
The method of claim 1 wherein the applied composition further includes a reducing compound that causes disruption of crosslinked keratin within keratinocytes of said epidermis.
Claim 48
Dependent Claim 18 words
The method of claim 46 wherein the reducing compound of said applied composition is a charged reducing compound.
Claim 49
Dependent Claim 27 words
The method of claim 1, further including the step of measuring electrical resistance across the stratus corneum during electroporation, whereby electroporation of said epidermis can be monitored.
Claim 50
Dependent Claim 27 words
The method of claim 1 further including the step of measuring electrical impedance across the stratus corneum during electroporation, whereby electroporation of said epidermis can be monitored.

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3.5 Years (Year 4) 2001-05-11 2001-11-10 2002-05-12 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 2005-05-11 2005-11-10 2006-05-12 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2009-05-11 2009-11-10 2010-05-12 $7700.00 Window Closed / Lapsed

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