US4880512A — Pulsed light selective photolysis process for tre…

Claim 1

Independent Claim 103 words

Process for treating a biological medium to photolyze nucleic acids in preference to proteins present therein, which comprises irradiating said medium with pulsed light of wavelength and flux selected so that (1) the nucleic acids in their ground state absorb radiation and thereby rise to an excited state or states, (2) the nucleic acids in their excited states absorb radiation and thereby rise to higher energy states and undergo photolysis to the extent that nucleic acid activity is reduced by at least 90%, and (3) the proteins in their ground or their excited states do not absorb sufficient radiation to undergo substantial photolysis.

Claim 2

Dependent Claim 103 words

Process for treating a biological medium to photolyze nucleic acids in preference to proteins present therein, which comprises irradiating said medium with pulsed light of wavelength and flux selected so that (1) the nucleic acids in their ground state absorb radiation and thereby rise to an excited state or states, (2) the nucleic acids in their excited states absorb radiation and thereby rise to higher energy states and undergo photolysis to the extent that nucleic acid activity is reduced by at least 90%, and (3) the proteins in their ground or their excited states do not absorb sufficient radiation to undergo substantial photolysis.

Claim 3

Dependent Claim 35 words

Process of claim 1 wherein the biological medium is a solution selected from blood, blood fractions, genetically engineered proteinaceous products of mammalian cells, and vaccine preparations containing viral DNA or RNA in a protein coat.

Claim 4

Dependent Claim 28 words

Process of claim 2 wherein the photolysis reduces nucleic acid activity by at least a factor of 10 4 and reduces protein functionality by no more than 40%.

Claim 5

Dependent Claim 61 words

Process of claim 3 wherein the biological medium is selected from whole blood, blood plasma, blood serum, blood factor VIII, and blood factor XI; said medium comprises nucleic acids in the form of DNA- or RNA-containing pathogens; and the photolysis reduces nucleic acid activity by at least a factor of 10 6 and reduces protein functionality by no more than 35%.

Claim 6

Dependent Claim 55 words

Process of claim 3 wherein the biological medium is a genetically engineered proteinaceous product of mammalian cells; said medium comprises nucleic acids in the form of active mamalian DNA or RNA; and the photolysis reduces nucleic acid activity by at least a factor of 10 6 and reduces protein functionality by no more than 35%.

Claim 7

Dependent Claim 59 words

Process of claim 3 wherein the biological medium is a vaccine preparation, said medium comprises nucleic acids in the form of viral DNA or RNA in a protein coat; and the photolysis reduces nucleic acid and thus viral activity by at least a factor of 10 4 and reduces functionality of the protein coat by no more than 40%.

Claim 8

Dependent Claim 36 words

Process of claims 4, 5 or 6 wherein the biological medium is an aqueous solution comprising tryptophan-containing proteins; the photolysis reduces substantially all of the nucleic acid activity, and reduces substantially none of the protein functionality.

Claim 9

Dependent Claim 18 words

Process of claim 1 wherein the pulsed light is comprised of laser pulses having substantially the same wavelength.

Claim 10

Dependent Claim 38 words

Process of claim 8 wherein each of said pulses has a wavelength within the range of 180 to 295 nm, a duration less than 1×10 -5 seconds and a flux greater than 1×10 15 photons per square centimeter.

Claim 11

Dependent Claim 44 words

Process of claim 9 wherein said wavelength is 220 to 290 nm, said duration is in the range of from 5×10 -9 to 1×10 -15 seconds, and said flux is in the range of from 1×10 5 to 1×10 18 photons per square centimeter.

Claim 12

Dependent Claim 44 words

Process of claim 9 wherein said wavelength is 220 to 280 nm, said duration is in the range of from 1×10 -10 to 1×10 -12 seconds, and said flux is in the range of from 1×10 17 to 1×10 18 photons per square centimeter.

Claim 13

Dependent Claim 16 words

Process of claim 1 wherein the pulsed light is comprised of laser pulses having different wavelengths.

Claim 14

Dependent Claim 81 words

Process of claim 12 wherein said laser pulses comprise one or more first pulse(s) of wavelength and flux selected so that said nucleic acids in their ground state absorb radiation and thereby rise to an excited state or states, one or more additional pulse(s) of wavelength and flux selected so that said nucleic acids in their excited states absorb radiation and thereby undergo photolysis, and said proteins do not absorb sufficient radiation from any of the pulses to undergo substantial photolysis.

Claim 15

Dependent Claim 40 words

Process of claim 13, wherein said excited states of nucleic acids are selected from the singlet state and the triplet state and wherein said additional pulse or pulses are applied during the lifetime of said excited states of nucleic acids

Claim 16

Dependent Claim 16 words

Process of claim 13 wherein said additional pulse or pulses comprise a second pulse or pulses.

Claim 17

Dependent Claim 13 words

Process of claim 15 wherein said first and second pulses are simultaneously applied.

Claim 18

Dependent Claim 21 words

Process of claim 16 wherein each of said second pulses is applied within 1 microsecond after each of said first pulses.

Claim 19

Dependent Claim 21 words

Process of claim 15 wherein said first and second pulses are applied in alternating sequences of more than one pulse each.

Claim 20

Dependent Claim 19 words

Process of claim 15 wherein said first and second pulses are applied in alternating sequences of one pulse each.

Claim 21

Dependent Claim 77 words

Process of claim 13 wherein each of said first pulses has a wavelength within the range of 180 to 350 nm, a duration of less than 1×10 -5 seconds, and a flux less than 1×10 18 photons per square centimeter, and each of said second pulses has a wavelength within the range of 300 to 700 nm, a duration of less than 1×10 -5 seconds and a flux of greater than 1×10 15 photons per square centimeter.

Claim 22

Dependent Claim 99 words

Process of claim 20 wherein each of said first pulses has a wavelength within the range of 180 to 295 nm, a duration of from 1×10 -10 to 1×10 -14 seconds, and a flux of 1×10 13 to 5×10 14 photons per square centimeter, and each of said second pulses has a wavelength within the range of 500 to 560 nm, a duration in the range of 1×10 -10 to 1×10 -12 seconds, a flux of 1×10 15 to 1×10 18 photons per square centimeter, and each second pulse is applied within 3×10 -12 seconds of each first pulse.

Claim 23

Dependent Claim 98 words

Process of claim 20 wherein each of said first pulses has a wavelength within the range of 180 to 295 nm, a duration of from 1×10 -5 to 1×10 -10 seconds, and a flux of 1×10 13 to 5×10 14 photons per square centimeter, and each second pulse has a wavelength within the range of 300 to 450 nm, a duration in the range of from 5×10 -9 to 1×10 -12 seconds, a flux of 1×10 15 to 1×10 18 photons per square centimeter, and each second pulse is applied within 1×10 -6 seconds of each first pulse.

Claim 24

Dependent Claim 39 words

Process for treating a biological fluid containing nucleic acids and proteins, which comprises irradiating said fluid with a plurality of laser pulses of wavelength and intensity selected so that said nucleic acids are photolyzed in preference to said proteins.

Claim 25

Dependent Claim 39 words

Process for treating a biological fluid containing nucleic acids and proteins, which comprises irradiating said fluid with a plurality of laser pulses of wavelength and intensity selected so that said nucleic acids are photolyzed in preference to said proteins.

Claim 26

Dependent Claim 47 words

Process of claim 23, wherein said laser pulses comprise a first pulse of a first wavelength and flux sufficient to raise a substantial portion of said nucleic acids from their ground state to an excited state, yet not sufficient to photolyze a substantial portion of said proteins.

Claim 27

Dependent Claim 45 words

Process of claim 24, wherein said laser pulses further comprise a second pulse which is preferentially absorbed by the nucleic acids in said excited state, but not substantially by said proteins, to thereby cause photolysis of said nucleic acids while minimizing photolysis of said proteins.

Claim 28

Dependent Claim 40 words

Process of claim 23 wherein each of said pulses has substantially the same wavelength within the range of 180 to 295 nm, a duration less than 1×10 -5 seconds and a flux greater than 1×10 15 photons per square centimeter.

Claim 29

Dependent Claim 44 words

Process of claim 26 wherein said wavelength is 220 to 290 nm, said duration is in the range of from 5×10 -9 to 1×10 -12 seconds, and said flux is in the range of from 1×10 15 to 1×10 18 photons per square centimeter.

Claim 30

Dependent Claim 45 words

Process of claim 27 wherein said wavelength is 220 to 280 nm, said duration is i n the range of from 1×10 -10 to 1×10 -12 seconds, and said flux is in the range of from 1×10 17 to 1×10 18 photons per square centimeter.

Claim 31

Dependent Claim 17 words

Process of claim 23 wherein said pulses comprise first and second pulses which have different wavelengths respectively.

Claim 32

Dependent Claim 77 words

Process of claim 29 wherein each of said first pulses has a wavelength within the range of 180 to 350 nm, a duration of less than 1×10 -5 seconds, and a flux less than 1×10 18 photons per square centimeter, and each of said second pulses has a wavelength within the range of 300 to 700 nm, a duration of less than 1×10 -5 seconds and a flux of greater than 1×10 15 photons per square centimeter.

Claim 33

Dependent Claim 99 words

Process of claim 30 wherein each of said first pulses has a wavelength within the range of 180 to 295 nm, a duration of from 1×10 -10 to 1×10 -14 seconds, and a flux of 1×10 13 to 5×10 14 photons per square centimeter, and each of said second pulses has a wavelength within the range of 500 to 560 nm, a duration in the range of 1×10 -10 to 1×10 -12 seconds, a flux of 1×10 15 to 1×10 18 photons per square centimeter, and each second pulse is applied within 3×10 -12 seconds of each first pulse.

Claim 34

Dependent Claim 98 words

Process of claim 31 wherein each of said first pulses has a wavelength within the range of 180 to 295 nm, a duration of from 1×10 -5 to 1×10 -10 seconds, and a flux of 1×10 13 to 5×10 14 photons per square centimeter, and each second pulse has a wavelength within the range of 300 to 450 nm, a duration in the range of from 5×10 -9 to 1×10 -12 seconds, a flux of 1×10 15 to 1×10 18 photons per square centimeter, and each second pulse is applied within 1×10 -6 seconds of each first pulse.

Claim 35

Independent Claim 124 words

A method of treating a solution of proteins and nucleic acids to selectively inactivate said nucleic acids, comprising: (a) irradiating said solution with a first light pulse of a first wavelength of sufficient flux to raise a portion of said nucleic acids from their ground state to an excited state yet not sufficient to inactivate the proteins in said solution; and (b) irradiating said nucleic acids while in said excited state with a second light pulse which is preferentially absorbed by nucleic acids in said excited state but not substantially by proteins in their ground state, to raise said nucleic acids to energy states higher than said excited state to thereby cause photolysis of said nucleic acids while minimizing the photolysis of said proteins.

Claim 36

Independent Claim 124 words

A method of treating a solution of proteins and nucleic acids to selectively inactivate said nucleic acids, comprising: (a) irradiating said solution with a first light pulse of a first wavelength of sufficient flux to raise a portion of said nucleic acids from their ground state to an excited state yet not sufficient to inactivate the proteins in said solution; and (b) irradiating said nucleic acids while in said excited state with a second light pulse which is preferentially absorbed by nucleic acids in said excited state but not substantially by proteins in their ground state, to raise said nucleic acids to energy states higher than said excited state to thereby cause photolysis of said nucleic acids while minimizing the photolysis of said proteins.

Claim 37

Dependent Claim 39 words

The method of claim 33, wherein said excited state comprises nucleic acid in its triplet state or singlet state and wherein said second pulse is applied during the triplet or singlet lifetime of said portion of said nucleic acids.

Claim 38

Dependent Claim 14 words

The method of claim 33, wherein said first and second pulses are simultaneously applied.

Claim 39

Dependent Claim 20 words

The method of claim 33 wherein said second light pulse is applied within 1 picosecond after said first light pulse.

Claim 40

Dependent Claim 18 words

The method of claim 33 wherein the wavelength of said first pulse is between 220 and 280 nanometers.

Claim 41

Dependent Claim 18 words

The method of claim 33 wherein the duration of said first pulse is less than 2×10 -8 seconds.

Claim 42

Dependent Claim 21 words

The method of claim 33 wherein the duration of said first pulse is between about 1×10 -12 and 9×10 -10 seconds.

Claim 43

Dependent Claim 22 words

The method of claim 33 wherein said first pulse has a flux of less than about 5×10 14 photons per square centimeter.

Claim 44

Dependent Claim 24 words

The method of claim 40 wherein said first pulse has a flux of between about 1×10 13 and 5×10 14 photons per square centimeter.

Claim 45

Dependent Claim 16 words

The method of claim 33 wherein said second pulse has a wavelength above about 350 nanometers.

Claim 46

Dependent Claim 19 words

The method of claim 42 wherein said second pulse has a wavelength of between about 350 to 410 nanometers.

Claim 47

Dependent Claim 19 words

The method of claim 43 wherein said second pulse has a wavelength of between about 500 to 560 nanometers.

Claim 48

Dependent Claim 18 words

The method of claim 33 wherein said second pulse has a duration of less than 2×10 -8 seconds.

Claim 49

Dependent Claim 21 words

The method of claim 45 wherein said second pulse has a duration of between about 9×10 -10 to 1×10 -12 seconds.

Claim 50

Dependent Claim 23 words

The method of claim 33 wherein said second pulse has a flux of about 1×10 15 to 1×10 18 photons per square centimeter.

Claim 51

Dependent Claim 20 words

The method of claim 47 wherein said second pulse has a flux of about 1×10 17 photons per square centimeter.

Claim 52

Dependent Claim 14 words

The method of claim 33 wherein said light pulses are pulses of laser light.

Claim 53

Dependent Claim 15 words

The method of claim 49 wherein said light pulses are applied by a single laser.

Claim 54

Dependent Claim 29 words

The method of claim 33 wherein said solution is located as a thin layer in a target region, said layer having a thickness of less than about 0.5 nm.

Claim 55

Dependent Claim 15 words

The method of claim 51 wherein said layer has a thickness of about 0.2 nm.

Claim 56

Dependent Claim 26 words

The method of claim 52 wherein said solution is flowed across each millimeter of target region width at a rate of about 5 milliliters per second.

Claim 57

Dependent Claim 15 words

The method of claim 33 wherein said solution is a blood fraction comprising plasma proteins.

Claim 58

Dependent Claim 38 words

The method of claim 54 wherein said blood fraction further comprises blood cells, and wherein said pulses are applied from a plurality of directions to strike substantially all of the plasma and serum disposed around said blood cells.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1992-11-13	1993-05-15	1993-11-14	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	1996-11-13	1997-05-15	1997-11-14	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2000-11-13	2001-05-15	2001-11-14	$7700.00	Window Closed / Lapsed

Pulsed light selective photolysis process for treatment of biological media and products made thereby

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