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 .
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 12 and 13 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 12 recites the limitation "the NHC" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 13 is rejected due to its dependence from claim 12.
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 non-obviousness.
Claims 1-3, 8, 9, 11, 14, 15, 17, 19, 21, 22, 24, 26-29, 31, 33-38, 41, 43 and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2018/0340063) in view of Elisseeff (US 2014/0112890).
Regarding claim 1, Liu et al. disclose a nerve conduit (Figure 6) comprising a tubular body having a proximal aperture and a distal aperture, wherein the proximal aperture has a diameter greater than a diameter of the distal aperture (¶[0048]), wherein the tubular body comprises a wall comprising a nanofiber diameter and pore size sufficient to allow diffusion of nutrients while preventing inflammatory macrophage infiltration (¶[0046], [0047], [0113]).
Liu et al. fail to disclose that a lumen of the conduit comprises one or more agents for inhibiting axonal growth, polarizing macrophages to the pro-regenerative phenotype, inhibiting axonal outgrowth, and combinations thereof. Liu et al. disclose that the conduit has a lumen that can be filled with a suitable adhesive (¶[0049]).
Elisseeff discloses an adhesive (Title) for repair of neural tissue (¶[0180]) comprising a CSPG-containing hydrogel (Abstract) which has reduced toxicity, strong adhesion and a controllable degradation rate (¶[0002]). A CSPG-containing hydrogel would inhibit axonal outgrowth as evidenced by ¶[0004] of Applicant’s published application.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have provided the CSPG hydrogel of Elisseeff in the lumen of the conduit of Liu et al. in order to provide an adhesive with reduced toxicity, strong adhesion and a controllable degradation rate.
Liu et al. disclose that the conduit can have a conical shape that tapers in decreasing diameter from the proximal aperture to the distal aperture (¶[0048]; Figure 6) but fail to disclose a specific taper angle as claimed. However, the claimed taper range is the maximum conceivable taper range bounded by whole numbers to describe a narrowing taper. At least some taper angles within this range would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention since Liu et al. disclose that the tube has at least some distally narrowing taper.
Regarding claims 2 and 3, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have provided the tubular body with a right conical shape since this is the standard form and most well-known form of a cone. A right cone has straight sides and therefore providing this shape would require a linear increase in diameter size as claimed. Furthermore, Liu et al. disclose that the diameter can vary in a continuous manner (¶[0048])
Regarding claim 8, CSPG-containing hydrogel can be regarded as a tissue matrix-derived hydrogel.
Regarding claim 9, the nanofiber tubular body above when filled with the above hydrogel can be regarded as a nanofiber hydrogel composite.
Regarding claim 11, the one or more bioactive agents that inhibit axonal outgrowth are CSPGs (Abstract of Elisseeff).
Regarding claim 14, the hydrogel has an overall stiffness of between 50-500 Pa (¶[0038] of Elisseeff - soft tissue having a modulus within this range).
Regarding claim 17, the tubular body comprises a nanofiber mesh wall having; a substantially uniform thickness ranging from about 50 m to about 500 m and with a pore size of less than about 10 m; and/or randomly oriented nanofibers having a diameter ranging from about 100 nm to about 2um (¶[0047]; [0113] of Liu).
Regarding claim 19, the nanofiber mesh wall comprises a synthetic material selected from poly(s-caprolactone) (PCL), copolymers of e-caprolactam and hexamethylendiaminadipate, polyglycolic acid (PGA), poly(lactic acid) (PLA), poly (1-lactic acid) (PLLA), copolymers of PLA and PGA, poly(lactic- co-glycolic acid) (PLGA), poly(vinyl acetate) (PVA), poly(ethylene-co-vinyl acetate) (PEVA), poly(ethylene glycol) (PEG), polyurethanes (PU), poly(ethylene oxide) (PEO), poly(vinyl pyrrolidone) (PVP), poly(ethylene terephthalate) (PET), poly(glycerol sebacate) (PGS), polydioxanone (PDO), polyphosphazenes (PPHOs), polyhydroxyalkanoates (PHA), polyhydroxybutyrates (PHB), polyhydroxyvalerate (PHV), polyhydroxyhexanoate (PHH), and polyhydroxyoctanoate (PHO), as well as co-polymers, blends, analogs, derivatives, modifications, and mixtures thereof; and/or a natural material selected from hyaluronic acid (HA), silk, keratin, collagen, gelatin, fibrinogen, elastin, actin, myosin, cellulose, amylose, dextran, chitin, glycosaminoglycans(GAG), deoxyribonucleic acids (DNA), ribonucleic acids (RNA), chitin, chitosan (CS), alginate, as well as co-polymers, blends, analogs, derivatives, modifications, and mixtures thereof (¶[0034], [0111] of Liu et al.).
Regarding claim 21, It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have provided the tubular body with a smooth wall since Liu et al. disclose that the diameter of the tubular body can taper in a continuous manner (¶[0048]).
Regarding claims 22 and 24, a crimped wall is not required by the claim if a smooth wall is provided when addressing claim 21.
Regarding claims 26 and 27, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have provided the tubular body with the sutures or extensions as seen in Figure 7 of Liu et al. in order to provide additional fixation of the conduit to a nerve.
Regarding claim 28, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have provided the sutures with a diameter within a range of the thickness of the conduit (100um-2mm; ¶[0046], [0047] of Liu et al.)so that the overall profile of the device is not substantially increased.
Regarding claims 29 and 33, Liu et al. disclose that the apertures can have a diameter within the range of 0.5-5 mm (¶[0046]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have provided the apertures with a diameter within the claimed ranges (“about” creating a range) since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233.
Regarding claim 31, Liu et al. fail to disclose that the tubular body has a length of about 5 mm to 50 mm. However, Liu et al. teach that nerve gaps needing repair can be 40 mm (¶[0004]). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have provided the tubular body with a length of about 50 mm so that it could adequately span across a nerve gap.
Regarding claim 34, Liu et al. disclose a method of providing the nerve conduit of claim 1 and contacting a large caliber injured nerve with the proximal aperture of the nerve conduit and contacting a small caliber nerve with the distal aperture (¶[0048]). Liu et al. fail to specifically state that the small caliber nerve is a sensory nerve. However, the conduit of Liu et al. is intended to repair injured peripheral nerves (¶[0003], [0004]). Sensory nerves are a well-known type among the peripheral nerves. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the conduit of Liu et al. to repair a sensory nerve as claimed in order to apply the advantages of the Liu et al. conduit to this well-known nerve type.
Regarding claim 35, the nerve comprises a peripheral nerve (¶[0003], [0004]).
Regarding claim 36, Liu et al. disclose that their conduit is intended to repair injured peripheral nerves (¶[0003], [0004]) but fail to disclose which specific tissues are repaired. However, it is well-known in the art that peripheral nerves of the muscles can become injured and require repair. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the conduit of Liu et al. to repair peripheral nerves of the muscles and thereby reinnervate these tissues.
Regarding claim 37, Liu et al. fail to disclose that the injured nerve is the result of a limb amputation. However, it is well-known in the art to reattach an amputated limb such as an arm and repair peripheral nerves therein. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the conduit and method of Liu et al. to repair nerves of an amputated limb such as an arm in order apply the advantages of the Liu et al. conduit to this well-known nerve repair procedure.
Regarding claims 38 and 43, Liu et al. disclose that their conduit is intended to repair injured peripheral nerves (¶[0003], [0004]) but fail to disclose which specific tissues are repaired. However, it is well-known in the art that peripheral nerves of the muscles can become injured and require repair. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the conduit of Liu et al. to repair peripheral nerves of the muscles and thereby reinnervate these tissues. The successful repair of a damaged muscle nerve would prevent the formation of a neuroma. Since Liu et al. do not disclose that a hydrogel is used, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have not provided such a composition to the lumen. Repair of a sensory nerve from a muscle would improve signal transduction from the muscle.
Regarding claim 41, the repair of a sensory nerve would cause reinnervation of the tissue it serves. The conduit of Liu et al. is intended to repair size-mismatched nerves (¶[0048]). Furthermore, it is well-known in the art to repair mixed nerves (having both sensory and motor nerve transfers). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the conduit of Liu et al. to repair a mixed nerve having motor and sensory nerve transfers in order to apply the advantages of the Liu et al. conduit to repair of this well-known nerve type.
Regarding claim 46, providing a prosthesis is not required by the claimed method. Repairing motor nerves using the conduit of Liu et al. as made obvious above can be considered as improving prosthesis control in some way. For example, a patient having restored motor function in almost any tissue would be better able to control some type of prosthesis in some way.
Response to Arguments
Applicant’s arguments with respect to the pending claims are either moot in view of the new grounds of rejection or are not persuasive. Applicant has argued that one of ordinary skill in the art would not be motivated by Elisseeff to modify the conduit of Liu to provide inhibitory cues to regenerating axons within the lumen to prevent excess axonal sprouting. Applicant has further argued that the benefits cited for the Elisseeff adhesive are not relevant to the instantly claimed invention. Obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the motivation to combine the teachings of Elisseeff need not be influenced by the intent of Applicant’s invention.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/THOMAS MCEVOY/Primary Examiner, Art Unit 3771