DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Objections
Claim 5 is objected to because of the following informalities:
change claim 5 accordingly: “a plurality of vibration elements, each of the plurality of vibration elements having a vibration peak”
change claim 6 accordingly: “said plurality of vibration elements”
Appropriate correction is required.
Drawings
It is noted that the following reference character(s) not mentioned in the description: L1,L2,L3 (see fig. 2) are incorporated by reference via US 2018/0369484 par. 79; see applicant par. 53) and thus the drawings were not objected to regarding this.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 line 6 recites “the bi-phasic injection profile has (i) at least two peaks within 15 msec from the injecting” (one or ordinary skill in the art would interpret this to mean that the injecting occurs and then within 15 msec after the injection the two peaks occur). Claim 1 lines 4-5 recites “the injecting exhibits a bi-phasic injection profile comprising a first phase and a second phase”. Thus “the injecting” includes “the bi-phasic injection profile”. Therefore it is unclear how the two peaks can occur after the injecting because the two peaks are included with the injecting. Applicant par. 35 states “The term ‘from the injecting’ herein may mean starting from the time that a pressure is starting to be applied to the naked nucleic acid molecule or the vaccine thereof and/or the time that an increase of pressure on the naked nucleic acid molecule or the vaccine thereof is detected.” However this is not a deliberate special definition at least because of the use or “may mean”. For purposes of compact prosecution the instant phrase is interpreted regarding from the time of the start of for example an injection mechanism (for example applicant par. 76 states “On average, the peaks for the first and second phases were detected at 5.230 msec and 24.150 msec after ignition”) or according to the instant applicant par. 35 (i.e. when the nucleic acid begins to be propelled or detected to be propelled; “detected” refers to detecting the nucleic acid exiting the nozzle of an injector enroute to a destination such as a human organ wherein a load cell at the exit of the nozzle is the pressure sensor that is a destination for the purposes of measuring the pressure profile, see applicant par. 75; a similar discussion is in Nagamatsu par. 64).
Claim 1 line 6 recites “the bi-phasic injection profile has (i) at least two peaks within 15 msec from the injecting” (one of ordinary skill in the art would interpret this to mean that the injecting occurs and then within 15 msec after the injection the two peaks occur). Claim 1 lines 4-5 recites “the injecting exhibits a bi-phasic injection profile comprising a first phase and a second phase”. Thus “the injecting” includes “the bi-phasic injection profile”. Therefore it is unclear how the two peaks can occur after the injecting because the two peaks are included with the injecting. Applicant par. 35 states “The term ‘from the injecting’ herein may mean starting from the time that a pressure is starting to be applied to the naked nucleic acid molecule or the vaccine thereof and/or the time that an increase of pressure on the naked nucleic acid molecule or the vaccine thereof is detected.” However this is not a deliberate special definition at least because of the use or “may mean”. For purposes of compact prosecution the instant phrase is interpreted regarding from the time of the start of for example an injection mechanism (for example applicant par. 76 states “On average, the peaks for the first and second phases were detected at 5.230 msec and 24.150 msec after ignition”) or according to the instant applicant par. 35 (i.e. when the nucleic acid begins to be propelled or detected to be propelled; “detected” refers to detecting the nucleic acid exiting the nozzle of an injector enroute to a destination such as a human organ wherein a load cell at the exit of the nozzle is the pressure sensor that is a destination for the purposes of measuring the pressure profile, see applicant par. 75; a similar discussion is in Nagamatsu par. 64). Claim 3 recites a similar limitation and is rejected for the same reasons.
Claim 1 lines 7-8 recites “the highest peak of the second phase of the bi-phasic injection within 30 msec from the injecting” (one of ordinary skill in the art would interpret this to mean that the injecting occurs and then within 30 msec after the injection the highest peak occur). Claim 1 lines 4-5 recites “the injecting exhibits a bi-phasic injection profile comprising a first phase and a second phase”. Thus “the injecting” includes “the bi-phasic injection profile”. Therefore it is unclear how the two peaks can occur after the injecting because the two peaks are included with the injecting. Applicant par. 35 states “The term ‘from the injecting’ herein may mean starting from the time that a pressure is starting to be applied to the naked nucleic acid molecule or the vaccine thereof and/or the time that an increase of pressure on the naked nucleic acid molecule or the vaccine thereof is detected.” However this is not a deliberate special definition at least because of the use or “may mean”. For purposes of compact prosecution the instant phrase is interpreted regarding from the time of the start of for example an injection mechanism (for example applicant par. 76 states “On average, the peaks for the first and second phases were detected at 5.230 msec and 24.150 msec after ignition”) or according to the instant applicant par. 35 (i.e. when the nucleic acid begins to be propelled or detected to be propelled; “detected” refers to detecting the nucleic acid exiting the nozzle of an injector enroute to a destination such as a human organ wherein a load cell at the exit of the nozzle is the pressure sensor that is a destination for the purposes of measuring the pressure profile, see applicant par. 75; a similar discussion is in Nagamatsu par. 64).
Claim 1 recites the limitation "the first peak" in line 7. There is insufficient antecedent basis for this limitation in the claim. Claim 4 also recites “the first peak”.
Claim 1 recites the limitation "the first peak" in line 7. Conditions (i), (ii) and (iii) are recited in the alternative (i.e., see “or” in line 7). Thus it is unclear if the instant first peak 1. refers to the one of the two peaks in condition (i), or 2. is separate from the condition (i) at least two peaks. For purposes of compact prosecution the claim is interpreted as the condition (i) peaks and the condition (ii) peak as not being related. It is thought that of the conditions (i), (ii) and (iii) should not provide antecedent basis for each other because they are alternative limitations.
Claim 1 recites the limitation "the highest peak" in line 7. There is insufficient antecedent basis for this limitation in the claim (there is no highest peak if the peaks are the same height).
Claim 1 recites the limitation "the highest peak" in line 7. Conditions (i), (ii) and (iii) are recited in the alternative (i.e., see “or” in line 7). Thus it is unclear if the instant highest peak 1. refers to the one of the two peaks in condition (i) and/or the first peak of condition (ii), or 2. is separate from the condition (i) and (ii) peaks. For purposes of compact prosecution the claim is interpreted as the condition (i) and (ii) peaks and the condition (iii) highest peak as not being related. It is thought that of the conditions (i), (ii) and (iii) should not provide antecedent basis for each other because they are alternative limitations.
Claim 1 recites the limitation "the bi-phasic injection" in lines 7-8. There is insufficient antecedent basis for this limitation in the claim. There is only antecedent basis of a b-phasic injection profile.
Claim 2 lines 1-2 recites “at least two peaks”. It is unclear the instant two peaks 1. refer to the claim 1 line 6 “at least two peaks” or 2. are different peaks. For purposes of compact prosecution the claim is interpreted regarding scenario 1. More specifically it is not clear if the instant phrase is intended to invoke claim 1 condition (i) or alternatively if the instant phrase is intended to apply to any of the claim 1 conditions (i), (ii) and (iii).
Claim 3 line 2 recites “at least two peaks”. It is unclear the instant two peaks 1. refer to the claim 1 line 6 “at least two peaks” or 2. are different peaks. For purposes of compact prosecution the claim is interpreted regarding scenario 1. More specifically it is not clear if the instant phrase is intended to invoke claim 1 condition (i) or alternatively if the instant phrase is intended to apply to any of the claim 1 conditions (i), (ii) and (iii).
Claim 4 recites “within 5 msec”. It is unclear if the instant limitation 1. refers to the time duration of the first peak of condition (ii), or 2. refers to a narrowing of the range (from 15msec to 5msec) of a first peak of condition (i). For purposes of compact prosecution the claim is interpreted regarding either scenario 1. or 2.
Claim 9 recites the limitation "the highest peak of the second phase" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim.
claim 9 line 3 recites “a first phase”. It is unclear if the instant first phase 1. refers to the claim 1 line 4 “first phase” or 2. is a different first phase.
Claim 9 recites the limitation "the bi-phasic profile" in lines 2 and 3. There is insufficient antecedent basis for this limitation in the claim. There is only antecedent basis for a bi-phasic injection profile.
Claim 10 recites the limitation "the highest peak" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim.
claim 10 line 3 recites “a first phase”. It is unclear if the instant first phase 1. refers to the claim 1 line 4 “first phase” or 2. is a different first phase.
Claim 10 recites the limitation "the bi-phasic profile" in lines 2 and 3. There is insufficient antecedent basis for this limitation in the claim.
Claims dependent thereon are rejected for the same reasons.
Claim Rejections - 35 USC § 102/103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-10 and 14 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by Pub. No.: US 2018/0369484 A1 (Nagamatsu) as evidenced by 2004/0191269 A1 (Lu) or, in the alternative, under 35 U.S.C. 103 as obvious over Nagamatsu in view of Lu.
Regarding claim 1, Nagamatsu discloses a method of administering a naked (with a “water-based” dosing liquid, see par. 38; one of ordinary skill in the art would consider this to meet the claimed “naked” of the type discussed in applicant par. 21; for example applicant par. 74 discusses “water” and also discusses water based “saline” in par. 26; this is evidenced by Lu par. 76) nucleic acid molecule (see par. 38) to a subject (see “human skin” in par. 45), comprising injecting the naked nucleic acid molecule to the subject, wherein the injecting exhibits a bi-phasic injection profile (this can be interpreted as a pressure versus time profile during injection; there is not required to be one or more peaks in any particular phase; this is consistent with applicant par. 28, bottom; “phase” can be interpreted as “An aspect; a part”, https://www.thefreedictionary.com/phase; thus the first and second phase can be shown in fig. 4(b), the division of the two instant phases being at any location on the “msec” axis; alternatively the first phase can be shown in fig. 4(b) and the second phase can be shown in fig. 4(a) after for example 8 or 10 msec) comprising a first phase (for example see S1,S2,S3,S4 in in fig. 4(b) during time from 5 to 7 msec) and a second phase (see for example Py in fig. 4(a) at from approx. time 12 to 24 msec), the second phase being after (see fig. 4(b), or both figs. 4(a) and 4(b)) the first phase, and the bi-phasic injection profile has (i) at least two peaks (see fig. 4(b); there are 4 peaks within 7 msec) within 15 msec from the injecting (this is interpreted as from the start of the injection process such start being for example when an injection button of an injector is pressed corresponding with ignition and time=0 in fig. 4(b); see 112 section above; this is consistent with applicant par. 76), (ii) the first peak of at least 2 MPa (see fig. 4(b) wherein all four peaks at S1,S2,S3,S4 are above 2MPa; it is noted the cycles S1,S2,S3,S4 are used to identify peaks herein wherein the peak refers to the highest portion of the cycle, see par. 65 bottom discussing vibration elements S1,S2,S3,S4 identified as “cycles”), or (iii) the highest peak (see fig. 4(a); at Py that is about 37 MPa) of the second phase (the second phase beginning at time 6.5 seconds for example) of the bi-phasic injection within 30 msec (see fig. 4(a) highest peak at about 18 msec compared to peaks S3,S4 that are less than 35 MPa) from the injecting.
In the scenario wherein one of ordinary skill in the art would not consider the nucleic acid of Nagamatsu to be naked nucleic acid then it can be said that Nagamatsu does not disclose a naked nucleic acid.
Lu teaches a naked nucleic acid (see par. 76) wherein the Lu naked nucleic acid is in water as pointed out in par. 76 (wherein the nucleic acid of Nagamatsu is in a “water-based liquid” that “need only be a substance preferable for administering the prescribed substances”; see Nagamatsu par. 38). It is further noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.” KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 at 1395 (U.S. 2007) (MPEP 2143 I.B.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to substitute the water or saline of Lu for the water-based liquid of Nagamatsu for the purpose of substituting one known element for another in order to provide the expected result of administering a naked nucleic acid and to facilitate using a physiological compatible solution (see Lu par. 76).
Regarding claim 2, Nagamatsu discloses the bi-phasic injection profile has at least two peaks (see fig. 4(b); there are 4 peaks within 7 msec) within 15 msec (see fig. 4(b)) from the injecting.
Regarding claim 3, Nagamatsu discloses wherein the bi-phasic injection profile has at least two peaks (L1,L2) within 1.5 msec (see fig. 4(b)) from the injecting. At about 4.9 msec (see par. 65) a pressure is starting to be applied to the naked nucleic acid molecule and/or there is an increase of pressure on the naked nucleic acid molecule and at the two peaks S1,S2 occur by about 5.9 msec (the value of the instant two peaks being Px1 and Px2).
Regarding claim 4, Nagamatsu discloses wherein the bi-phasic injection profile has the first peak (see peaks S1,S2,S3,S4 in fig. 4(b)) within 5 msec (see fig. 4(b); the instant peaks occur within 5 msec of the start of pressurization of the dosing liquid at about 4.9 msec.
Regarding claim 5, Nagamatsu discloses wherein the first phase comprises a plurality of vibration elements (see “pressure vibration elements S1 to S4” in par. 65), each of the plurality of vibration elements having a vibration peak (see fig. 4(b)). The term “vibration element” is interpreted as a special definition regarding applicant par. 37 “one cycle in which injection pressure rises and drops in pressure vibration is to be handled as one pressure vibration element”. There is a similar statement in Nagamatsu par. 65 however it was not clear to examiner if the Nagamatsu statement could be considered an ordinary and customary plain meaning definition (for example because vibration element is also considered to be a piezo related element in the medical arts; e.g., see US 20160331308 par. 231)
Regarding claim 6, Nagamatsu discloses wherein total amplitudes of said plurality of vibration elements (see “pressure vibration elements S1 to S4” in par. 65; see fig. 4(b)) decrease over time (see par. 66 and fig. 4(b); also see par. 71: “Through this process, the total amplitude of the respective vibration elements gradually decreases”).
Regarding claim 7, Nagamatsu discloses wherein the first peak is at least 2 MPa. See fig. 4(b) peaks S1,S2,S3,S4 that are all over 2Ma. Claim 1, condition (ii) only requires one peak and thus each of the instant peaks can be a first peak.
Regarding claim 8, Nagamatsu discloses wherein the highest peak (see fig. 4(a); at Py that is about 37 MPa) of the second phase (the second phase beginning at time 6.5 seconds for example) of the bi-phasic injection profile is at least 0.1 MPa. The second phase can include peaks S3,S4 for example and also include peak Py, all of which peaks are greater than 0.1 MPa (see figs. 4(a) and 4(b)).
Regarding claim 9, Nagamatsu discloses wherein the highest peak of the second phase (time duration that includes peaks S3,S4) of the bi-phasic profile is lower than the highest peak of a first phase (time duration that includes peaks S1,S2) of the bi-phasic profile. Peak S3 is lower than peak S1 (see fig. 4(b)).
Regarding claim 10, Nagamatsu discloses wherein the highest peak of the second phase (time duration for example including peaks S4 and Py) of the bi-phasic profile is higher than the highest peak of a first phase (time duration for example that includes peaks S1,S2,S3) of the bi-phasic profile. Peak Py is higher than peak S1 (see figs. 4(a) and 4(b)).
Regarding claim 14, Nagamatsu discloses wherein the naked nucleic acid molecule is injected with a needleless injector (see par. 34).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nagamatsu in view Lu.
Regarding claim 11, Nagamatsu discloses the current invention as claimed and discussed above. Nagamatsu does not disclose wherein the naked nucleic acid molecule is injected only with a buffer.
Lu teaches injecting naked nucleic acid with needleless injector (see par. 76) and further teaches the naked nucleic acid molecule is injected only (the injected nucleic acid is naked except for the buffer) with a buffer (see par. 76 regarding for example saline or Tris-EDTA (TE) buffer).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to provide Nagamatsu with wherein the naked nucleic acid molecule is injected only with a buffer as taught by Lu in order to facilitate to provide a stable pH and prevent degradation of the solution to be injected.
Claim(s) 12 and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nagamatsu as evidenced by Lu, in view of US 2011/0123637 A1 (Pascolo), or in the alternative over Nagamatsu in view of Lu as applied to claim 1 above and further in view of Pascolo.
Regarding claims 12 and 13, Nagamatsu discloses, on in the alternative Nagamatsu in view of Lu teach, the current invention as claimed and discussed above. Nagamatsu does not disclose wherein the naked nucleic acid molecule is mRNA; wherein the mRNA is injected in an amount of at least 0.2 μg.
Pascolo teaches injection with a needleless injector (see par. 91) and further teaches injecting naked mRNA (see par. 56); wherein the mRNA is injected in an amount of at least 0.2 μg (see par. 56).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to provide Nagamatsu, or in the alternative Nagamatsu in view of Lu, with wherein the naked nucleic acid molecule is mRNA; wherein the mRNA is injected in an amount of at least 0.2 μg as taught by Pascolo in order to facilitate improved safety (see Pascolo par. 3) optimal clinical procedures (see Pascolo par. 9) regarding laboratory testing (see Pascolo par. 56).
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
US 20020055729: injection of naked DNA (par. 49) with needleless injector 10 (fig. 1A); and
naked mRNA injection: US 20160166710 (par. 499)
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARC J AMAR whose telephone number is (571)272-9948. The examiner can normally be reached M-F 9:00-6:00.
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/MARC AMAR/Examiner, Art Unit 3741 /DEVON C KRAMER/Supervisory Patent Examiner, Art Unit 3741
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