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 .
Claims 1-21 have been cancelled. Claims 22-37 are newly presented. Applicant's election without traverse of Group I, claims 22-37, and the species of claims 25-27, in the reply filed on 17 October 2025 is acknowledged. Claims 28-30 have been withdrawn. Claims 22-27 and 31-37 are currently pending and under examination.
This application is a continuation of U.S. Patent Application No. 15/164463, filed May 25, 2016, now U.S. Patent No. 11,513,039, which is a continuation-in-part of U.S. Patent Application No. 14/724365, filed May 28, 2015, now U.S. Patent No. 11,156,595.
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 22-27 and 31-37 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 22 recites in relevant part “determining a potency of the acellular nerve graft based at least in part on the determined amount of outgrowing nerve structure” (emphasis added). This claim is indefinite, because it is unclear how else potency is intended to be determined, as “at least in part” indicates that other factors are intended to considered. Applicant does not provide a definition for “potency,” or indicate what factors, in addition to an amount of outgrowing nerve structure, should be used to make this determination. As such, the metes and bounds of this claim are unclear.
Claims 23-27 and 31-37 are included in this rejection as these claims depend from above rejected claim 22, and fail to remedy the noted deficiencies.
Claim Rejections - 35 USC § 102
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.
Claims 22-25, 27, and 31-37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cullen et al. (IDS; WO 2015/066627; Published 7 May 2015).
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With regard to claim 22, referring to Figures 9A-B and 10 reproduced here, Cullen et al. teach attaching, which is affixing, at least one neuron to a first end (uni-directional), or a first and second end (bi-directional), of a micro-engineered neural network (Micro-TENNs), which is an acellular nerve graft (Abs.; Fig. 9A-B, 10; p. 6, line 4-21; p. 17, line 31 to p. 18, line 5; p. 35, line 33 to p. 36, line 3), thus forming a test construct.
The test construct is cultured in a medium for a period of time sufficient to allow nerve outgrowth from the neuron(s) into the acellular nerve graft (Abs.; Fig. 9A-B, 10; p. 17, line 31 to p. 18, line 5; p. 35, line 33 to p. 36, line 3).
The length of one or more neurites is measured to determine the rate of neurite penetration (p. 37, line 1-9; p. 42, line 7-15; p. 5, line 5-12 (Fig. 2)), which is performing an analysis of the test construct to determine an amount of outgrowing nerve structure based on a length of one or more peripheral nerve structures.
As the neurites are measured and shown to grow in length (see for example Fig. 2; p. 5, line 5-12), this outgrowing nerve structure provides a determination of activity, which is potency, of the acellular nerve graft.
As Cullen et al. teach the method as claimed, including the steps as claimed, the taught method is conducting a bioassay of an acellular nerve graft.
With regard to claim 23, Cullen et al. teach measuring the outgrowth of the neurites present in the construct (Figs. 2, 10; p. 5, line 5-12), and measuring MAP-2, a microtubule-associated protein expressed primarily in neuronal somata and dendrites (p. 36, line 12-19), which is determining the amount of outgrowing nerve structure based on the length of one or more peripheral nerve structures and the amount of the target protein.
With regard to claim 24, Cullen et al. teach measuring the outgrowth of the multiple neurites present in the construct (Figs. 2, 10; p. 5, line 5-12), which is determining the amount of outgrowing nerve structure based on the length of two or more peripheral nerve structures associated with the outgrowing nerve structure.
With regard to claim 25, Cullen et al. teach that the length of one or more neurites is measured to determine the rate of neurite penetration (p. 37, line 1-9; p. 42, line 7-15; p. 5, line 5-12 (Fig. 2)), which is performing an analysis of the test construct to determine an amount of outgrowing nerve structure based on a length of one or more peripheral nerve structures. Where analysis of the test construct is performed by flash freezing tissue samples that include the test construct to a chuck to prepare the test construct for sectioning; sectioning the frozen and fixed test construct into a plurality of 20 µm sections, which is removing the sections longitudinally at a predetermined distance from a side of the acellular nerve graft perpendicular to the first end; and straining each section with multiple stains (p. 37, line 14-32).
With regard to claim 27, Cullen et al. teach that the stains include β-Tubulin III (Fig. 1; p. 4, line 31-33).
With regard to claim 31, Cullen et al. teach that the outgrowing nerve structure is a neurite (Fig. 10; p. 7, line 10-21).
With regard to claim 32, teach that following fabrication, the acellular nerve graft is sterilized under UV light prior to affixing the neurons (p. 35, line 1-5), which inhibits the bioactivity of bacteria, and thus is passivating the acellular nerve graft.
With regard to claim 33, Cullen et al. teach that the neuron(s) are cultured in the acellular nerve graft for a period including 7 days (Fig. 4B, p. 5, line 27-29), which is fully encompassed within about 3 days to about 7 days.
With regard to claim 34, Cullen et al. teach that the acellular nerve graft is a hydrogel with a bioactive matrix core that includes collagen, where the neuron(s) is attached thereto (see Fig. 9B; p. 3, line 1-3; claims 21-24). As such, the neuron(s) is affixed to the acellular nerve graft with a collagen gel.
With regard to claims 35 and 36, Cullen et al. teach that the neuron(s) attached to the acellular nerve graft is from a human or an animal (p. 3, line 19-20). As such, the acellular nerve graft comprising the attached neuron(s) is deemed to be taken from a human or animal.
With regard to claim 37, Cullen et al. teach that the length of neurite penetration in the acellular nerve graft is measured at weekly timepoints, and the average neurite length at each time point is calculated (p. 39, line 1-2). Thus, the length of the one or more peripheral nerve structures is an average of lengths of more than one peripheral nerve structure.
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 22, 25, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Cullen et al., and further in view of Kokkat et al. (Archived Formalin-Fixed Paraffin-Embedded (FFPE) Blocks: A Valuable Underexploited Resource for Extraction of DNA, RNA, and Protein, Biopreservation and Biobanking, Vol. 11, No. 2, (2013), pp. 101-106).
The teachings of Cullen et al. as applied to claims 1 and 25 have been set forth above.
With regard to claim 26, while Cullen et al. teach preparing the test construct for sectioning including fixing the test construct (p. 37, line 14-32), it is not specifically taught that the test construct is paraffin-embedded.
Kokkat et al. teach that paraffin embedding of tissue preserves the morphology and cellular detail of the tissue sample, and long-term storage of paraffin-embedded blocks at ambient temperature is more cost efficient than storing frozen tissues (p. 101, Left col., Para. 1).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Cullen et al. and Kokkat et al., because both teach the freezing of tissue samples. The use of paraffin-embedding of tissue samples is known in the art as taught by Kokkat et al. The use of paraffin-embedding as taught by Kokkat et al. in place of freezing the tissue sections of Cullen et al. amounts to the simple substitution of one know type of tissue fixation for another, and would have been expected to predictably and successfully provide a tissue section as desired for further study. Additionally, paraffin-embedding as taught by Kokkat et al. would have the added benefit of providing a tissue section that can be stored at ambient temperature, and thus is more cost effective storing the frozen sections.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 22-27 and 31-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 8, 9, and 12-17 of U.S. Patent No. 11,156,595. Although the claims at issue are not identical, they are not patentably distinct from each other because both encompass a method for conducting a bioassay of an acellular nerve graft, comprising affixing a neuron to an acellular nerve graft to form a test construct; culturing the test construct in a medium for a period of time to allow nerve outgrowth from the neuron or the group of neurons into the acellular nerve graft; performing an analysis of the test construct to determine an amount of outgrowing nerve structure based on a length of one or more peripheral nerve structures, an amount of a target protein, and/or an amount of mRNA for a target protein associated with the outgrowing nerve structure; and determining a potency of the acellular nerve graft based at least in part on the determined amount of outgrowing nerve structure; wherein the neuron is affixed with collagen gel; and wherein the length is an average of lengths of more than one nerve structure (Present claims: 22-24, 34, 37; Cited patent claims: 1, 8).
Analysis of the test construct comprises preparing the test construct for sectioning; sectioning the test construct into a plurality of sections, wherein each of the plurality of sections is removed longitudinally at a predetermined distance from a side of the acellular nerve graft perpendicular to the first end; and staining each section with one or more stains; fixing includes paraffin-embedding; and stains/target proteins include βIII-Tubulin (Present claims: 25-27; Cited patent claims: 2, 3, 9). The outgrowing nerve structure is a neurite or a Schwann cell (Present claims: 31; Cited patent claims: 12). The method further comprises passivating the acellular nerve graft prior to affixing the neuron or group of neurons onto the acellular nerve graft (Present claims: 32; Cited patent claims: 13-15). The period of time for culturing is from about 3 days to about 7 days (Present claims: 33; Cited patent claims: 16). The acellular nerve graft is taken from a human or animal, and can thus be an allograft (Present claims: 35, 36); Cited patent claims: 17).
Claims 22-27 and 31-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 7-16, and 18-20 of U.S. Patent No. 11,513,039. Although the claims at issue are not identical, they are not patentably distinct from each other because both encompass a method for conducting a bioassay of an acellular nerve graft, comprising affixing a neuron to an acellular nerve graft to form a test construct; culturing the test construct in a medium for a period of time to allow nerve outgrowth from the neuron or the group of neurons into the acellular nerve graft; performing an analysis of the test construct to determine an amount of outgrowing nerve structure based on a length of one or more peripheral nerve structures, an amount of a target protein, and/or an amount of mRNA for a target protein associated with the outgrowing nerve structure; and determining a potency of the acellular nerve graft based at least in part on the determined amount of outgrowing nerve structure; wherein the neuron is affixed with collagen gel; and wherein the length is an average of lengths of more than one nerve structure (Present claims: 22-24, 34, 37; Cited patent claims: 1, 7, 12, 15, 19).
Analysis of the test construct comprises preparing the test construct for sectioning; sectioning the test construct into a plurality of sections, wherein each of the plurality of sections is removed longitudinally at a predetermined distance from a side of the acellular nerve graft perpendicular to the first end; and staining each section with one or more stains; fixing includes paraffin-embedding; and stains/target proteins include βIII-Tubulin (Present claims: 25-27; Cited patent claims: 2-4, 8, 16). The outgrowing nerve structure is a neurite or a Schwann cell (Present claims: 31; Cited patent claims: 9, 18). The method further comprises passivating the acellular nerve graft prior to affixing the neuron or group of neurons onto the acellular nerve graft (Present claims: 32; Cited patent claims: 10, 20). The period of time for culturing is from about 3 days to about 7 days (Present claims: 33; Cited patent claims: 11). The acellular nerve graft is taken from a human or animal, and can thus be an allograft (Present claims: 35, 36); Cited patent claims: 13, 14).
Claims 22-27 and 31-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 13-20 of U.S. Patent No. 11,959,903. Although the claims at issue are not identical, they are not patentably distinct from each other because both encompass a method for conducting a bioassay using an acellular nerve graft, comprising affixing a neuron to an acellular nerve graft to form a test construct; culturing the test construct in a medium for a period of time to allow nerve outgrowth from the neuron or the group of neurons into the acellular nerve graft; performing an analysis of the test construct to determine an amount of outgrowing nerve structure based on a length of one or more peripheral nerve structures, an amount of a target protein, and/or an amount of mRNA for a target protein associated with the outgrowing nerve structure; and determining a potency of the acellular nerve graft based at least in part on the determined amount of outgrowing nerve structure; wherein the neuron is affixed with collagen gel; and wherein the length can include an average of lengths of more than one nerve structure (Present claims: 22-24, 34, 37; Cited patent claims: 1-3, 13, 15, 19).
Analysis of the test construct comprises preparing the test construct for sectioning; sectioning the test construct into a plurality of sections, wherein each of the plurality of sections is removed longitudinally at a predetermined distance from a side of the acellular nerve graft perpendicular to the first end; and staining each section with one or more stains; fixing includes paraffin-embedding; and stains/target proteins include βIII-Tubulin (Present claims: 25-27; Cited patent claims: 6, 7, 9, 14, 16). The outgrowing nerve structure is a neurite or a Schwann cell (Present claims: 31; Cited patent claims: 17). The method further comprises passivating, including by submerging the acellular nerve graft in a test solution, prior to affixing the neuron or group of neurons onto the acellular nerve graft (Present claims: 32; Cited patent claims: 1, 4, 5). The period of time for culturing is from about 3 days to about 7 days (Present claims: 33; Cited patent claims: 18). The acellular nerve graft is taken from a human or animal, and can thus be an allograft (Present claims: 35, 36); Cited patent claims: 13-15).
Claims 22-27 and 31-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 8-16 of U.S. Patent No. 11,885,792. Although the claims at issue are not identical, they are not patentably distinct from each other because both encompass a method for conducting a bioassay using an acellular nerve graft, comprising affixing a neuron to an acellular nerve graft to form a test construct; culturing the test construct in a medium for a period of time to allow nerve outgrowth from the neuron or the group of neurons into the acellular nerve graft; performing an analysis of the test construct to determine an amount of outgrowing nerve structure based on a length of one or more peripheral nerve structures, an amount of a target protein, and/or an amount of mRNA for a target protein associated with the outgrowing nerve structure; and determining a potency of the acellular nerve graft based at least in part on the determined amount of outgrowing nerve structure; wherein the neuron is affixed with collagen gel; and wherein the length includes an average of lengths of more than one nerve structure (Present claims: 22-24, 34, 37; Cited patent claims: 1-3, 8, 13, 16).
Analysis of the test construct comprises preparing the test construct for sectioning; sectioning the test construct into a plurality of sections, wherein each of the plurality of sections is removed longitudinally at a predetermined distance from a side of the acellular nerve graft perpendicular to the first end; and staining each section with one or more stains; fixing includes paraffin-embedding; and stains/target proteins include βIII-Tubulin (Present claims: 25-27; Cited patent claims: 4-6, 9). The outgrowing nerve structure is a neurite or a Schwann cell (Present claims: 31; Cited patent claims: 10). The method further comprises passivating the acellular nerve graft prior to affixing the neuron or group of neurons onto the acellular nerve graft (Present claims: 32; Cited patent claims: 11). The period of time for culturing is from about 3 days to about 7 days (Present claims: 33; Cited patent claims: 12). The acellular nerve graft is taken from an animal or a human (Present claims: 35, 36; Cited patent claims: 14, 15).
Claims 22-27 and 31-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8-10, and 12-15 of U.S. Patent No. 12,326,440. Although the claims at issue are not identical, they are not patentably distinct from each other because both encompass a method for conducting a bioassay using an acellular nerve graft, comprising affixing a neuron to an acellular nerve graft to form a test construct; culturing the test construct in a medium for a period of time to allow nerve outgrowth from the neuron or the group of neurons into the acellular nerve graft; performing an analysis of the test construct to determine an amount of outgrowing nerve structure based on a length of one or more peripheral nerve structures; and determining a potency of the acellular nerve graft based at least in part on the determined amount of outgrowing nerve structure; wherein the neuron is affixed with collagen gel; and wherein the length can include an average of lengths of more than one nerve structure (Present claims: 22-24, 34, 37; Cited patent claims: 1, 9).
Analysis of the test construct comprises preparing the test construct for sectioning; sectioning the test construct into a plurality of sections, wherein each of the plurality of sections is removed longitudinally at a predetermined distance from a side of the acellular nerve graft perpendicular to the first end; and staining each section with one or more stains; fixing includes paraffin-embedding; and stains/target proteins include βIII-Tubulin (Present claims: 25-27; Cited patent claims: 4-6). The outgrowing nerve structure is a neurite or a Schwann cell (Present claims: 31; Cited patent claims: 12). The method further comprises passivating, including by submerging the acellular nerve graft in a test solution, prior to affixing the neuron or group of neurons onto the acellular nerve graft (Present claims: 32; Cited patent claims: 2, 3, 8). The period of time for culturing is from about 3 days to about 7 days (Present claims: 33; Cited patent claims: 10). The acellular nerve graft is taken from an animal, which includes a human (Present claims: 35, 36); Cited patent claims: 20).
Conclusion
No claims are allowable.
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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653