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 .
This Office Action is in response to the paper filed June 10, 2026. Claims 3, 4, and 11-15 remain withdrawn. Claims 1, 2, 5, 6, 8, 9, and 16-20 are currently pending and under examination.
This Application is a national phase application under 35 U.S.C. §371 of International Application No. PCT/US2018/054576, filed October 5, 2018, which claims priority to U.S. Provisional Application No. 62/569,255, filed October 6, 2017.
Maintenance of Rejections:
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.
Claims 1, 2, 5, 6, 8, 9, and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Pfister et al. (Development of transplantable nervous tissue constructs comprised of stretch-grown axons, Journal of Neuroscience Methods, Vol. 153, (2006), pp. 95-103 – Previously Presented), as evidenced by McGill (The McGill Physiology Virtual Lab, Accessed 8/22/23, Available online at: www. medicine.cgill.ca/physio/vlab/other_exps/CAP/nerve_anat.Htm#:~: text=For%20example%2C%20the%20vagus%20nerve,ganglia%2C%20for%20sensory%20fibres – Previously Presented), and further in view of Sretavan (IDS; US 2007/0067883; Published 2007).
With regard to claims 1, 2, and 6, Pfister et al. teach a nerve construct including a tissue engineered fasciculated axon tract that is stretch-grown in vitro, and developed into nervous tissue constructs designed to span peripheral nerve or spinal cord lesions in a subject (Abs.; Figs. 2-7). The tissue engineered fasciculated axon tract is implanted to treat a nerve injury in a subject by contacting the site of the nerve injury with the tissue engineered fasciculated axonal tract, wherein axons in the tissue engineered fasciculated axonal tract fuse with axons from the subject when contacted with the site of the nerve injury (see Fig. 7).
While Pfister et al. teach that the axons are in a plurality of fascicularized bundles (see for example, Fig. 4 C-E, Fig. 5 B), the number of axons in a bundle(s) is not specifically taught. However, it would have been obvious to one of ordinary skill in the art to determine the number of axonal tracts necessary for treating the specific nerve injury in a subject, based on the number of axons in native tissue. For example, the vagus nerve in a human consists of over 100,000 axons (see McGill, p. 1, Background). It is noted that "the discovery of an optimum value of a variable in a known process is usually obvious." Pfizer v. Apotex, 480 F.3d at 1368. The rationale for determining the optimal parameters for prior art result effective variables "flows from the 'normal desire of scientists or artisans to improve upon what is already generally known.'" Id. (quoting In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)). Accordingly, it would have been obvious to optimize the number of axons in the tissue engineered axonal tract, including to more than about 100,000 axons, to result in a nerve graft effective for treatment of the specific nerve injury in the subject.
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Additionally, referring to Fig. 7 reproduced below, it is clear from the teachings of Pfister et al. that treating the nerve injury may include severing a proximal stump at the site of the nerve injury, and contacting the proximal stump with the nerve construct that includes a tissue engineered fasciculated axon tract (see Fig. 7 A). Thus, it would have been obvious to an ordinary artisan from the teachings of Pfister et al. to sever a proximal stump at the site of the nerve injury, and contact the proximal stump with the tissue engineered fasciculated axon tract.
While Pfister et al. further teach in an embodiment where the subject axons fuse to the axons of the implanted tissue engineered fasciculated axon tract (see Fig. 7(C)), Pfister et al. do not teach that the axons in the tissue engineered fasciculated axon tract are severed from their neuronal cell bodies.
Sretavan teach a method of treating a nerve injury in a subject, including by severing a proximal stump at a site of nerve injury, contacting the proximal stump with a tissue engineered axonal tract, where the tissue engineered axonal tract fuses with the axon from the subject when contacted with the proximal stump (Abs.; Fig. 1-2). The method involves fabrication and use of a Micro Electromechanical Systems (MEMS) axon surgery platform that can cut and remove damaged axon segments and enable the splicing together of transected segments of host with donor axons (Para. 19).
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Fig. 1 shows the surgical repair of damaged axons to achieve functional connection of nerves by “excision of the damaged axon region and the spicing in of a healthy segment from a donor axon” (emphasis added) (Para. 21).
As such, Sretavan teach that only the donor axonal tract, which does not include neuronal cell bodies, is utilized for splicing with the host axons to treat the nerve injury.
It would have been obvious to one of ordinary skill in the art to combine the teaching of Pfister et al. and Sretavan, because both teach nerve repair using tissue engineered axonal tracts. The use of a tissue engineered axonal tract, where the axons have been severed from their neuronal cell bodies, and thus only the donor and host axons are spliced together, is known in the art as taught by Sretavan. The use of a tissue engineered axonal tract, where the axons have been severed from their neuronal cell bodies, and thus only the donor and host axons are spliced together and fuse, as the tissue engineered fasciculated axon tract in the method of Pfister et al., amounts to the simple substitution of one known axonal tract (axon only) for another (axon + neuronal cell body). The use of tissue engineered fasciculated axon bundles that include only the separated axons would have been expected to predictably and successfully provide an alternative donor axon graft for repair of damaged nerve tissue.
With regard to claims 5 and 9, Pfister et al. teach that the tissue engineered fasciculated axon tract may be useful for extensive nerve repair in a chronic state, even after the distal transected nerve has degenerated (p. 101, full paragraph 2, lines 12-18). Thus, it would have been obvious to an ordinary artisan from the teachings of Pfister et al. that the implanted nerve construct containing the tissue engineered fasciculated axon tract would further provide the result of regeneration of a distal nerve segment in a subject, and be useable for treating a nerve injury resulting from a neurodegenerative disease.
With regard to claim 8, Pfister et al. as evidenced by McGill do not specifically teach that the method includes application of a hypotonic 50% by weight solution of PEG to the site of injury. Sretavan teach a method of treating a nerve injury in a subject by contacting a site of a nerve injury with a tissue engineered axonal tract (Abs.; Fig. 1-2). Sretavan further teach that PEG can be used to promote fusion following axon cutting and alignment (Para. 165). While it is not specifically taught that the PEG is applied in a hypotonic solution comprising 50% by weight of PEG, it is noted that a PEG solution would necessarily either be hypotonic, hypertonic, or isotonic. As such, it would have been obvious to one of ordinary skill in the art to determine the appropriate type of solution to utilize with the PEG, including hypotonic, as most appropriate for the specific injury to be treated.
In addition, Sretavan further teach that lower percentages of PEG, including 5%, have been utilized to facilitate fusion where laser fusion is also applied (Para. 166). It would have been obvious to one of ordinary skill in the art to determine the most appropriate concentration of PEG based on other fusion techniques being utilized. Additionally, please also note that "the discovery of an optimum value of a variable in a known process is usually obvious." Pfizer v. Apotex, 480 F.3d at 1368. The rationale for determining the optimal parameters for prior art result effective variables "flows from the 'normal desire of scientists or artisans to improve upon what is already generally known.'" Id. (quoting In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)). Accordingly, it would have been obvious to optimize the concentration of the PEG in the hypotonic solution, including to 50% by weight, to result in the use of an effective amount of PEG based on any additional fusion techniques being utilized, and the injury being treated.
It would have been obvious to one of ordinary skill in the art to combine the teaching of Pfister et al. and Sretavan, because both teach nerve repair using tissue engineered axonal tracts. The use of PEG for application to the site of the injury, is known in the art as taught and rendered obvious by Sretavan. The use of PEG for application to the site of the injury would have been expected to predictably improve the method of Pfister et al., as it is known from the teachings of Sretavan that PEG can desirably be used to promote fusion following axon cutting and alignment.
Claims 16-20 are directed to the tissue engineered axonal tract, which is produced by the claimed process. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Here, the tissue engineered axonal tract of Pfister et al. and Sretavan et al. includes axons, which are similarly distributed in a plurality of fascicularized bundles and severed from their neuronal bodies. The tissue engineered axonal tract is used for the same purpose as claimed: for treating a nerve injury in a subject. Functionally, the tissue engineered axonal tract of Pfister et al. and Sretavan et al. is the same as the claimed tissue engineered axonal tract. Therefore, the tissue engineered axonal tract of Pfister et al. and Sretavan et al. is the same as, or would have rendered obvious, the tissue engineered axonal tract produced by the processes in claims 16-20.
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"The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature" than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an unobvious difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 798, 802, 218 USPQ 289, 292 (Fed. Cir. 1983).
Response to Arguments
Applicant urges that Pfister does not disclose or suggest direct axon fusion, and instead teaches axon regeneration for the reasons set forth by Applicant (see Applicant’s arguments, 6/10/2026, C., p. 6, to p. 9).
Applicant’s arguments have been fully considered, but have not been found persuasive.
Although Examiner disagrees with Applicant’s characterization of Fig. 7A, whether fusion or regeneration is shown in the referenced figure is immaterial. In response to applicant's argument that Pfister does not disclose or suggest direct axon fusion, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
It is noted that the claimed limitation being relied upon by Applicant specifically states: “wherein when the tissue engineered axonal tract contacts the site of nerve injury, at least one axon from the tissue engineered axonal tract fuses with at least one axon from the subject” (emphasis added). This limitation is not a method step. It recites a result of performing the one claimed method step in claim 1 of “contacting a site of nerve injury with a tissue engineered axonal tract comprising more than 100,000 axons distributed among a plurality of fascicularized bundles”; or the two method steps in claim 2 of “severing a proximal stump at a site of nerve injury,” and “contacting the proximal stump with a tissue engineered axonal tract comprising more than 100,000 axons distributed among a plurality of fascicularized bundles, the axons being severed from their neuronal cell bodies.” Applicant is essentially arguing that performance of the same method step(s) provide different results. This is not found persuasive, as the result of performing the method step(s) as claimed must naturally flow from performance of the method, unless an essential step or feature is missing from the claimed method.
Applicant urges that Sretavan describes a fundamentally incompatible technology that cannot be meaningfully combine with Pfister for the reasons set forth by Applicant (Applicant’s arguments, 6/10/2026, D., p. 9, to p. 11).
Applicant’s arguments have been fully considered, but have not been found persuasive.
Applicant indicates that Sretavan discloses categorically different technology from both Pfister and the claimed invention, and thus there is no rational basis for combining the references, or arriving at the claimed invention. Applicant discusses Sretavan in depth and compares the teachings of Sretavan to the instant invention. However, Applicant does not make this comparison between Sretavan and Pfister, and thus does not clearly set forth how the references are incompatible. Further, in comparing the method of Sretavan to the instant invention, Applicant includes numerous unclaimed features (e.g. implantation by conventional microsurgery, the preclusion of individual axon alignment, repair of specifically peripheral nerve injury, spinal cord injury, and brain injury; method of making the tracts by stretch-growth, etc.). While the claims are interpreted in light of the specification, it is improper to read limitations from the specification into the claims.
Applicant urges that the examiner’s previous response to arguments contain specific analytical errors, including that the invocation of In re Keller and In re Merck does not address Applicant’s combination-level arguments, and examiner’s reliance on Pfister’s Fig. 7 does not establish axon fusion, and the comparison of Pfister’s Fig. 7 to Sretavan’s Fig. 1 conflates regeneration with fusion (Applicant’s arguments, 6/10/2026, E., 1.-2., p. 11, to p. 13).
Applicant’s arguments have been fully considered, but have not been found persuasive.
Applicant’s combination level arguments (Applicant’s arguments, 6/10/2026, D., p. 9, to p. 11), have been addressed previously. Further, Applicant’s arguments regarding Pfister’s Fig. 7 and the claimed results not being taught (Applicant’s arguments, 6/10/2026, C., p. 6, to p. 9), have also been addressed previously.
Regarding Applicant’s argument about the lack of a KSR simple substitution analysis, as discussed in Examiner’s previous response, the KSR obviousness rationale regarding the simple substitution of one known element for another, the analysis requires determination of:
(1) a finding that the prior art contained a device (method, product, etc.) which differed from the claimed device by the substitution of some components (step, element, etc.) with other components;
(2) a finding that the substituted components and their functions were known in the art;
(3) a finding that one of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable; and
(4) whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness (see MPEP 2143; I. B.).
As Examiner noted in the rejection, and with regard to above-noted (1) and (2), the use of a tissue engineered axonal tract, where the axons have been severed from their neuronal cell bodies, and thus only the donor and host axons are spliced together, is known in the art as taught by Sretavan. The use of a tissue engineered axonal tract, where the axons have been severed from their neuronal cell bodies, and thus only the donor and host axons are spliced together and fuse, as the tissue engineered fasciculated axon tract in the method of Pfister et al., amounts to the simple substitution of one known axonal tract (axon only) for another (axon + neuronal cell body). Further as Examiner noted in the rejection, and with regard to (3) and (4), the use of tissue engineered fasciculated axon bundles that include only the separated axons would have been expected to predictably and successfully provide an alternative donor axon graft for repair of damaged nerve tissue.
Applicant urges that the proposed combination would destroy the principle of operation of Pfister and would still not yield the claimed invention (Applicant’s arguments, 6/10/2026, F., p. 13, to p. 14).
Applicant’s arguments have been fully considered, but have not been found persuasive. It is noted that there is no requirement that the entirety of the teaching of a secondary reference be imported into, and compatible with, the primary reference. As discussed previously, the one claimed method step in claim 1 is: “contacting a site of nerve injury with a tissue engineered axonal tract comprising more than 100,000 axons distributed among a plurality of fascicularized bundles”; and in claim 2: “severing a proximal stump at a site of nerve injury,” and “contacting the proximal stump with a tissue engineered axonal tract comprising more than 100,000 axons distributed among a plurality of fascicularized bundles, the axons being severed from their neuronal cell bodies.” The method as currently claimed, especially with regard to the independent claims, does not required the reading in of all of the features of each reference discussed by Applicant. Further, it is noted that the discussed conceptual frameworks are not claimed requirements.
Applicant urges that dependent claims 5, 8, 9, and 16-20 are not rendered obvious for the reasons set forth (Applicant’s arguments, 6/10/2026, F., p. 14, to p. 16).
Applicant’s arguments have been fully considered, but have not been found persuasive.
Regarding dependent claims 5 and 9, Applicant urges that the subject matter of these claims is not disclosed. It is noted that claim 5 is directed to a result of performing the claimed method step, and does not set forth any additional steps. Similarly, claim 9 further characterizes the origin of injury in the subject treated by the method, which also does not set forth any additional steps for performing the claimed method.
Regarding dependent claim 8, Applicant urges that the brief recitation of the use of PEG in the reference is insufficient to render its use obvious, and to optimize the amount. As indicated in the rejection, Sretavan specifically teach that PEG can be used to promote fusion following axon cutting and alignment (Para. 165). While it is not specifically taught that the PEG is applied in a hypotonic solution comprising 50% by weight of PEG, it is noted that a PEG solution would necessarily either be hypotonic, hypertonic, or isotonic. As such, it would have been obvious to one of ordinary skill in the art to determine the appropriate type of solution to utilize with the PEG, including hypotonic, as most appropriate for the specific injury to be treated.
In addition, Sretavan further teach that lower percentages of PEG, including 5%, have been utilized to facilitate fusion where laser fusion is also applied (Para. 166). It would have been obvious to one of ordinary skill in the art to determine the most appropriate concentration of PEG based on other fusion techniques being utilized. Additionally, please also note that "the discovery of an optimum value of a variable in a known process is usually obvious." Pfizer v. Apotex, 480 F.3d at 1368. The rationale for determining the optimal parameters for prior art result effective variables "flows from the 'normal desire of scientists or artisans to improve upon what is already generally known.'" Id. (quoting In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)). Accordingly, it would have been obvious to optimize the concentration of the PEG in the hypotonic solution, including to 50% by weight, to result in the use of an effective amount of PEG based on any additional fusion techniques being utilized, and the injury being treated.
Regarding dependent claims 16-20, it is urged that the burden of establishing that the claimed product is the same as, or obvious in view of, the prior art has not been met. As noted in the rejection, the tissue engineered axonal tract of Pfister et al. and Sretavan et al. includes axons, which are similarly distributed in a plurality of fascicularized bundles and severed from their neuronal bodies. The tissue engineered axonal tract is used for the same purpose as claimed: for treating a nerve injury in a subject. Functionally, the tissue engineered axonal tract of Pfister et al. and Sretavan et al. is the same as the claimed tissue engineered axonal tract. Therefore, the tissue engineered axonal tract of Pfister et al. and Sretavan et al. is the same as, or would have rendered obvious, the tissue engineered axonal tract produced by the processes in claims 16-20.
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"The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature" than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an unobvious difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 798, 802, 218 USPQ 289, 292 (Fed. Cir. 1983).
For the forgoing reasons the obviousness rejection is maintained.
Conclusion
No claims are allowable.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER M.H. TICHY whose telephone number is (571)272-3274. The examiner can normally be reached Monday-Thursday, 9:00am-7:00pm ET.
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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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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
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