DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/09/2025 has been entered.
Claims 5 and 9-11 were examined on their merits.
Response to Amendment
The Declaration under 37 CFR § 1.130 filed 06/09/2025 is sufficient to overcome the rejection of claims 5 and 9-11 based in part, upon Leonhardt et al. (US 2017/0266371 A1) as set forth in the prior action.
The rejection of Claims 5, 10 and 11 under 35 U.S.C. § 103 as being
unpatentable over LaPlante et al. (2013) in view of Abidor et al. (1993), Neculaes et al. (US 9,452,199 B2), Kobayashi et al. (2016), and Leonhardt et al. (US 201 7/0266371
A1), as evidenced by Guo et al. (2008), all of record, has been withdrawn in view of the above noted Declaration.
The rejection of Claim 9 under 35 U.S.C. § 103 as being unpatentable over LaPlante et al. (2013) in view of Abidor et al. (1993), Neculaes et al. (US 9,452,199 B2),
Kobayashi et al. (2016), and Leonhardt et al. (US 2017/0266371 A1), as evidenced by
Guo et al. (2008), and further in view of Tsai et al. (2009), all of record, has been withdrawn in view of the above noted Declaration.
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 5 and 9-11 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 5 in part recites, “…wherein the bioelectric signal to upregulate expression of EGF is, within 15%, 10 V/cm, pulse-width 180 µs, 500 Hz.” It is unclear what the ”within 15%” limitation qualifies, whether it applies to one or all of the 10 V/cm, 180 µs pulse-width, 500 Hz limitations. Claims 9-11 are rejected as being dependent upon rejected Claim 5.
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.
Claim(s) 5, 10 and 11 are rejected under 35 U.S.C. § 103 as being unpatentable over LaPlante et al. (2013) in view of Abidor et al. (1993), both of record, Neculaes et al. (US 2017/0362571 A1), Kobayashi et al. (2016),of record, Kanno et al. (US 6,988,004 B2), and Guo et al. (2008), of record.
LaPlante et al. teaches a method of preparing platelet-rich plasma (PRP)
comprising centrifuging whole blood (Pg. 203, Column 2, Lines 41-47);
followed by applying a bioelectric signal (nanosecond pulsed electric field) to the prepared PRP by leads which are electronically connected to a nanosecond pulse generator and provide a pulsed electric field to the PRP (Pg. 204, Column 1, Lines 34- 42 and Pg. 205, Fig. 1), and reading on Claims 5 and 11.
LaPlante et al. teaches that activation of PRP with electric pulse stimulation leads to ex vivo release of several growth factors from human platelets in PRP (Pg. 202, Abstract) and that nanosecond pulsed electric fields (nsPEF) are hypothesized to cause calcium to leak out from intracellular stores as a result of nanopores being created in the organelles membrane, as well as in influx of extracellular calcium through plasma membrane nanopores (Pg. 203, Column 2, Lines 4-9).
LaPlante et al. further teaches that applying nsPEF to PRP causes increased release of PDGF, VEGF and EGF (Pg. 206, Figs. 4-6).
LaPlante et al. does not teach wherein the pulsed electric field (PEF) is applied during centrifugation of blood to form PRF by a centrifuge modified to provide the PEF via a bioelectric stimulator signal generator programmed to produce at least one bioelectric signal that upregulates expression of at least one of: PDGF, VEGF and EGF, thereby producing a PRF comprising PDGF, VEGF and/or EGF, wherein the bioelectric signal to upregulate expression of VEGF is 0.1 V applied at a frequency of 50 Hz, as required by Claims 5 and 10.
Abidor et al. teaches a centrifuge which provides electrical pulses during centrifugation through leads connected to each centrifugation chamber (Pg. 208, Column 1, Lines 46-49 and Fig. 1).
Abidor et al. further teaches that application of PEF results in membrane poration (Pg. 208, Column 2, Lines 34-35).
Neculaes et al. teaches a system including a non-transitory, computer-readable memory storing one or more processor executable routines (i.e., programming) which when activated, cause a sequence of one or more electric pulses to be applied to a blood sample to trigger release of a growth factor in the blood sample (Pg. 7, Claim 1);
wherein the blood is used to prepare PRP (Fig. 8);
and wherein the bioelectric signal causes PDGF release (Fig. 4).
Kobayashi et al. teaches that both PRP and PREF are prepared by centrifugation of whole blood (Pg. 2354, Column 2, Lines 3-27) and both release PDGF, VEGF and EGF ex vivo (Pg. 2356, Table 1).
Kanno et al. teaches a bioelectric stimulation to upregulate expression of VEGF wherein the bioelectric signal to upregulate VEGF expression is: 0.1 V applied at a frequency of 50 Hz (Column 9, Claim 1).
It would have been obvious to those of ordinary skill in the art before the effective filing of the claimed invention to modify the method of LaPlante et al. of preparing PRP by centrifuging blood and then electrically stimulating the PRP with the device of Abidor et al. which allows electrical stimulation to be applied during centrifugation because this is no more than the application of a known technique (electrical stimulation during centrifugation) to a known method (centrifugation of blood to prepare PRP followed by electrical stimulation) ready for improvement to yield predictable results (growth factor release caused electroporation of cell membranes). Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to eliminate a separate step of electrical stimulation after centrifugation. There would have been a reasonable expectation of success in making this modification because both references are reasonably drawn to the same field of endeavor, that is, the centrifugation and electrical stimulation/poration of cells.
It would have been further obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of providing electrical stimulation during the centrifugal preparation of PRP of LaPlante et al. and Abidor et al. with the programming of the electric pulse generator to produce at least one bioelectric signal as taught by Neculaes et al., wherein the programmed bioelectric signals is that taught by Kanno et al. because this is no more than the automation of a previously manual activity. Those of ordinary skill in the art would have been motivated to make this modification in order to eliminate the manual stimulation of PRP during centrifugation.
There would have been a reasonable expectation of success in making this modification because at least LaPlante et al. and Neculaes et al. are drawn to the same field of endeavor, that is the pulsed electrical stimulation of PRP.
It would have been further obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of providing electrical stimulation during the centrifugal preparation of PRP with the programming of the electric pulse generator to produce at least one bioelectric signal as taught by LaPlante et al., Abidor et al., Neculaes et al. and Kanno et al. with the substitution of PRP for the PRF as taught by Kobayashi et al. above, because Kobayashi teaches both PRP and PRF are prepared the same way (centrifugation of whole blood) and secrete the same growth factors PDGF, VEGF and EGF ex vivo. LaPlante et al. teaches that application of electrical stimulus to PRP causes platelet release ex vivo of said growth factors. Therefore, the ordinary artisan would reasonably expect that application of electrical stimulus to another platelet concentrate product (PRF) would also cause ex vivo release of said growth factors from the platelets therein. Those of ordinary skill in the art would have been motivated to make this modification in order to stimulate increased release of growth factors from the platelets in the PRF. There would have been a reasonable expectation of success in making this modification because at least LaPlante et al. and Neculaes et al. are drawn to the same field of endeavor, that is the pulsed electrical stimulation of PRP and Kobayashi et al. teaches that both PRP and PRF are prepared the same way and contain concentrated platelets.
With regard to Claim 5, the limitation of, “...at least one bioelectric signal during the centrifugation process that upregulates expression of at least one protein selected from the group consisting of platelet-derived growth factor (PGDF), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) in the PRF...” this would be inherent in the electrical stimulation of PRF and/or PRP because Guo et al. teaches that there is an overall positive correlation between MRNA and protein expression levels (Pg. 426, Abstract). Thus, the ordinary artisan would reasonably expect that a process of electrical stimulation of a platelet concentrate providing increased ex vivo release of protein growth factors requiring protein expression would also have a correlative increase in gene expression of said growth factors.
Claim 9 is rejected under 35 U.S.C. § 103 as being unpatentable over LaPlante et al. (2013) in view of Abidor et al. (1993), both of record, Neculaes et al. (US 2017/0362571 A1), Kobayashi et al. (2016), of record, Kanno et al. (US 6,988,004 B2), and Guo et al. (2008), as applied to Claims 5, 10 and 11 above, and further in view of Tsai et al. (2009), of record.
The teachings of LaPlante et al., Abidor et al., Neculaes et al., Kobayashi et al. and Kanno et al. were discussed above.
None of the above references taught a method wherein the centrifuge revolves at 3000 rpm during the centrifugation process, as required by Claim 9.
Tsai et al. teaches centrifugation of blood at 3000 rpm for the preparation of PRF
(Pg. 131, Column 2, Lines 6-16).
It would have been obvious to those of ordinary skill in the art before the effective
filing date of the claimed invention to modify the method of providing electrical
stimulation during the centrifugal preparation of PRF of LaPlante et al., Abidor et al.,
Neculaes et al., Kobayashi et al. and Kanno et al. with the centrifugation of blood at
3000 rpm as taught by Tsai et al. because the reference indicates that this is a suitable
centrifugation speed to prepare PRF. Those of ordinary skill in the art would have been
motivated to make this modification in order to prepare PRF by centrifuging at a known
speed to produce PRF. There would have been a reasonable expectation of success in
making this modification because Kobayashi et al. teaches that both PRP and PRF are
prepared by centrifugation of blood and Tsai et al. teaches a method for preparing PRF
by blood centrifugation.
Response to Arguments
Applicant’s arguments, see Remarks, filed 06/09/2025, with respect to the rejection(s) of claim(s) 5 and 9-11 under 35 U.S.C. § 103 have been fully considered and are persuasive. Therefore, the rejections have been withdrawn.
However, upon further consideration, a new ground(s) of rejection is made in view of LaPlante et al. (2013) in view of Abidor et al. (1993), both of record, Neculaes et al. (US 2017/0362571 A1), Kobayashi et al. (2016), of record, Kanno et al. (US 6,988,004 B2), and Guo et al. (2008), as set forth above.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653 08/11/2025