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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 30 September 2025 has been entered.
Claim 16 has been amended. Claims 17-20 are newly added. Claims 3, 4, and 11-15 remain withdrawn.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.
Withdrawal of Rejections:
The rejection of claim 16 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, is withdrawn.
Maintenance/Modification 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 no evidence is provided in support of Pfister’s alleged tissue engineered fasciculated axonal tract facilitating fusion with axons from a subject’s nerve injury, and Pfister does not describe the use of any axon tract severed from cell bodies in accordance with the definition of “tissue engineered axon tract” at p. 11, lines 21-22 of the instant specification. Additionally, Applicant urges that the evidence does not support the simple substitution of one known axonal tract for another. Pfister describes an “axon + neuronal cell body” for use in an integration process that does not involve severing axonal tracts or fusing axons to one another. In contrast, Sretavan is described for use in a completely different process for fusing together axons from a donor and a recipient. Substituting Pfister’s axon+neuronal cell body with Sretavan’s axon only tract would not work and would change the principle of operation of Pfister’s disclosed process.
Applicant’s arguments have been fully considered, but have not been found persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Here, Sretavan is cited for teaching that the axons are severed from their neuronal cell bodies. Additionally, it can be seen, for example in Fig. 7(C) of Pfister, that the tissue engineered fasciculated axonal tract facilitates fusion with axons from a subject’s nerve injury.
With regard to Applicant’s argument that the evidence does not support the simple substitution of one known axonal tract for another; as noted in the rejection, 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.
With regard to the KSR obviousness ration 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.
Further, comparing Pfister Fig. 7 and Srevetan Fig. 1 reproduced here:
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Pfister, Fig. 7 (C) shows that in a second possible repair process, regenerating axons from the host tissue grow through the lesion by following the transplanted axon pathway (see Fig. 7, Explanatory parenthetical). Which is an axon-axon attachment (host axons to axons of the implanted tract), similar to that of the process of Srevetan shown in Fig. 1. Thus, contrary to Applicant’s assertion, Pfister does teach fusing axons to one another and the simple substitution described would not change the principle of operation of Pfister’s disclosed process.
For the forgoing reasons, the obviousness rejection is maintained.
Conclusion
No claims are allowable.
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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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653