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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/20/2025 has been entered.
Election/Restrictions
Regarding claim 26, the elected species is: poly(glycerol sebacate) and poly(octamethylene maleate (anhydride) citrate) (POMaC).
Claim Objections
The previous claim objections are withdrawn in light of the amendments.
Claim 21 is objected to because of the following informalities:
Regarding claim 21, in line 13, the term “the sensing elements” should be “the at least two elastic sensing elements” for the sake of clarity.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The previous 35 U.S.C. § 112(b) rejections are withdrawn in light of the amendments.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 21-32, 41-42, and 44-45 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claim 21, the claim contains the following limitation that is not in the originally filed application: “the skeletal muscle tissue does not contract in the absence of electrical and/or chemical stimulation”.
Regarding the dependent claims 22-32, 41-42, and 44-45, these claims are rejected for the same reason as the base claim upon which they depend.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 21-32, 41, and 44-45 are rejected under 35 U.S.C. 103 as being unpatentable over Miklas (US 20160282338) in view of Bashir (US 10906169), further in view of evidentiary reference Betts (“10.2: Skeletal Muscle”).
Regarding claim 21, Miklas discloses a tissue system comprising a three-dimensional ex vivo skeletal muscle tissue (paragraphs [0173] for hydrogel; and for skeletal muscle cells [0177]) and a bioreactor (paragraph [0012]), wherein the three-dimensional ex vivo skeletal muscle tissue comprises a hydrogel (paragraph [0173]) mixture and a plurality of cells that includes skeletal muscle cells (paragraph [0177]), wherein at least a portion of the cells are encapsulated inside the hydrogel (paragraph [0173]), wherein the skeletal muscle tissue is characterized by one or more contractions in response to an electrical and/or chemical stimulation (see inherency argument 1, below for this property of skeletal muscle tissue), wherein the three-dimensional ex vivo skeletal muscle tissue does not contract in the absence of electrical and/or chemical stimulation (see inherency argument 2, below for this property of skeletal muscle tissue) and wherein the bioreactor (paragraph [0012]) comprises:
a device having a well (paragraph [0019]) configured for growing the three-dimensional ex vivo skeletal muscle tissue from the cells seeded therein (paragraphs [0019] and [0177]), wherein the well has a bottom (paragraph [0095], Fig. 37(a), hot embossing PMMA base); and
at least two elastic sensing elements (paragraphs [0095], [0103]-[0105], and [0773]; Fig. 37(d), polymer wires affixed thereon) disposed across the well (paragraph [0095], Fig. 37(d)) such that there is a gap between the at least two elastic sensing elements and the bottom of the well (paragraph [0093], Fig. 35; and paragraph [0021]), wherein the sensing elements are configured to: (a) permit attachment of the three-dimensional ex vivo skeletal muscle tissue formed there between, thereby suspending the three-dimensional ex vivo skeletal muscle tissue above the bottom of the well (paragraphs [0021] and [0024]), and (b) deform in response to a contractile force exerted on the sensing elements by the three-dimensional (paragraph [0022]) ex vivo skeletal muscle tissue (paragraphs [0173] and [0177]).
Miklas does not disclose:
a hydrogel mixture comprising thrombin
Regarding feature 1, Bashir discloses:
a hydrogel mixture comprising thrombin (col. 18, lines 8-31).
In the analogous art of muscle-powered biological machines, it would have been obvious to one skilled in the art before the effective filing date to modify Miklas with the thrombin of Bashir in order to cross-link the hydrogel comprising skeletal muscle cells into a stable 3D gel network and compaction of the muscle tissue (Bashir, col. 28, lines 34-37 and col. 49, lines 10-15).
Regarding inherency argument 1, the limitation “the skeletal muscle tissue is characterized by one or more contractions in response to an electrical and/or chemical stimulation”, this property is an inherent property to skeletal muscle tissue, as skeletal muscles contract in response to an electrical and/or chemical stimulation from the nervous system (see pgs. 7-10 of 10 of Betts “10.2: Skeletal Muscle”). Neurons acquire their ability to electrically signal from the ions present (or not present), so the Examiner also considers the electrical stimulation a chemical stimulation. Regarding the limitation “and/or chemical stimulation”, this limitation is claimed in the alternative, so no further rejections are needed at this time. Additionally, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Miklas would be fully capable of operating in this manner given the hydrogel and the skeletal muscle tissue.
Regarding inherency argument 2, the limitation “wherein the three-dimensional ex vivo skeletal muscle tissue does not contract in the absence of electrical and/or chemical stimulation”, skeletal muscle cells do not have the inherent ability to contract on their own (see pg. 7 of 10 of Betts “10.2: Skeletal Muscle”), and require a stimulus (such as an electrical and/or chemical stimulation of independent claim 21, such as a movement of ions across a membrane, usually due to efferent neuronal firing within the human body) (see pg. 7 of 10 of Betts “10.2: Skeletal Muscle”). Additionally, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Miklas would be fully capable of operating in this manner given the hydrogel and the skeletal muscle tissue.
Regarding claim 22, Miklas discloses at least two electrodes configured to apply an electrical stimulation (paragraphs [0020] and [0278]) to the three-dimensional ex vivo skeletal muscle tissue (paragraphs [0173] for hydrogel; and for skeletal muscle cells [0177]) of the bioreactor (paragraph [0012]).
Regarding claim 23, Miklas discloses wherein the at least two elastic sensing elements (paragraphs [0095], [0103]-[0105], and [0773]; Fig. 37(d), polymer wires affixed thereon) comprise a synthetic polymer (paragraph [0186]), a biologic polymer (paragraph [0186]), or a combination thereof (paragraph [0189]).
Regarding claim 24, Miklas discloses wherein the polymer is degradable (paragraph [0186]).
Regarding claim 25, Miklas discloses wherein the polymer is nondegradable (paragraph [0186]).
Regarding claim 26, Miklas discloses wherein each elastic sensing element comprises (paragraphs [0095], [0103]-[0105], and [0773]; Fig. 37(d), polymer wires affixed thereon) a polymer selected from the elected species: poly(glycerol sebacate) (paragraph [0228]) and poly(octamethylene maleate (anhydride) citrate) (POMaC) (paragraph [0227]).
Regarding the remainder of the claim, the remainder was not elected.
Regarding claim 27, Miklas discloses the polymer comprises POMaC (paragraph [0227]).
Regarding claim 28, Miklas discloses wherein the at least two elastic sensing elements (paragraphs [0095], [0103]-[0105], and [0773]; Fig. 37(d), polymer wires affixed thereon) have an elasticity somewhere within the range of 20 kPa to 0.5 MPa (paragraphs [0773]-[0775] and Figs. 45-47).
Miklas does not disclose the exact data and endpoints of the ranges in each experiment within its PGPub, as it only states “The elastic modulus … fall[s] right into the range of adult myocardium” (Miklas, paragraph [0773]), wherein the human myocardium was previously stated as being “from about 20 kPa to 0.5 MPa” (Miklas, paragraph [0773]).
However, because the above elasticity’s range is within the range of human myocardium according to Miklas, it is also within the claimed range of 10 kPa to 0.8 MPa; therefore, Miklas reads on the claimed limitation.
Regarding claim 29, Miklas discloses wherein the at least two elastic sensing elements (paragraphs [0095], [0103]-[0105], and [0773]; Fig. 37(d), polymer wires affixed thereon) are in the form of polymer wires (paragraph [0092] and [0773]).
Regarding claim 30, Miklas discloses wherein the bioreactor comprises 2 to 25 elastic sensing elements per well (paragraphs [0735]-[0736] “2 wires” or claim 88 “from 2 to 25”).
Regarding claim 31, Miklas discloses wherein the bioreactor comprises a multi-well plate (paragraphs [0736]-[0742] and Figs. 37a-d3 and 38a-c).
Regarding claim 32, Miklas discloses wherein the multi-well plate comprises
6 wells (paragraph [0737]), 12 wells (paragraph [0737]), 24 wells (paragraph [0737]), 96 wells (paragraphs [0737] and [0741]), 384 wells (paragraph [0737]), or 1536 wells (paragraph [0041]).
Regarding the remainder of the claim, “8 wells”, this limitation is claimed in the alternative; no further rejections are required at this time.
Regarding claim 41, Miklas discloses wherein the plurality of cells further comprises fibroblasts (paragraphs [0504] and [0512]; claim 98).
Regarding claim 44, Miklas discloses wherein the three-dimensional ex vivo skeletal muscle tissue is produced using a stimulation protocol comprising a plurality of pulses separated by no electrical stimulations (paragraphs [0595]-[0597] and [0608]).
Miklas does not disclose wherein the three-dimensional ex vivo skeletal muscle tissue is produced using a stimulation protocol comprising a plurality of pulses separated by no electrical stimulations, wherein each pulse is at least about 10 Hz applied for a duration of about one second.
Regarding the limitation, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Miklas would be fully capable of operating in this manner given the hydrogel and the skeletal muscle tissue. Also see MPEP 2113 (Product-by-Process Claims).
Regarding claim 45, Miklas discloses the three-dimensional ex vivo skeletal muscle tissue is produced using a stimulation protocol comprising a ramp rate (paragraphs [0596]-[0597]).
Miklas does not disclose the three-dimensional ex vivo skeletal muscle tissue is produced using a stimulation protocol comprising applying a first frequency for a first duration and a second frequency for a second duration, wherein the first frequency is increased to the second frequency at a ramp rate which is at least about 0.1 Hz/hour.
Regarding the limitation, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Miklas would be fully capable of operating in this manner given the hydrogel and the skeletal muscle tissue. Also see MPEP 2113 (Product-by-Process Claims).
Claim 42 are rejected under 35 U.S.C. 103 as being unpatentable over Miklas (US 20160282338) in view of Bashir (US 10906169) and evidentiary reference Betts (“10.2: Skeletal Muscle”) as applied to claim 41, further in view of Lancaster (US 20210290823).
Regarding claim 42, Miklas does not disclose wherein the fibroblasts and the skeletal muscle tissue are at a ratio of between about 1:5 and 1:50.
Lancaster discloses wherein the fibroblasts and the skeletal muscle tissue are at a ratio of between about 1:5 and 1:50 (paragraph [0008]).
In the analogous art of muscle cell patches, it would have been obvious to one skilled in the art before the effective filing date to modify modified Miklas with the ratio of fibroblasts and skeletal muscle tissue of Lancaster in order to provide a scaffold that is capable of spontaneous synchronized contractions across the surface of the scaffold (Lancaster, paragraph [0008]). Additionally, the contractile construct can be implanted in a subject in need thereof after culturing. The construct may be implanted prior to onset of cellular contraction and/or patch level contraction (Lancaster, paragraph [0007]).
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 21-32, 41-42, and 44-45 are directed to an invention not patentably distinct from the claims of commonly assigned 17/798047 (Radisic). Specifically:
Claims 21-22 and 41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 26-27 of copending Application No. 17/798047 (Radisic) in view of Bashir (US 10906169) and evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection.
Regarding claim 21, Radisic discloses a tissue system (claim 1) comprising a three-dimensional (claim 1) ex vivo skeletal muscle tissue (claims 26-27) and a bioreactor (claim 1, “at least one well”), wherein the three-dimensional ex vivo skeletal muscle tissue comprises a hydrogel (claim 26) and a plurality of cells that includes skeletal muscle cells (claim 27), wherein at least a portion of the cells are encapsulated inside the hydrogel (claim 26), wherein the skeletal muscle tissue is characterized by one or more contractions (claim 1) in response to an electrical stimulation (claim 1, see inherency argument 1, below), wherein the three-dimensional ex vivo skeletal muscle tissue does not contract in the absence of electrical and/or chemical stimulation (see inherency argument 2, below) and wherein the bioreactor comprises:
a device having a well (claim 1) configured for growing the three-dimensional ex vivo skeletal muscle tissue (claims 26-27) from the cells seeded therein (claim 26), wherein the well has a bottom (claim 1); and
at least two elastic sensing elements (claim 1) disposed across the well (claim 1) such that there is a gap between the at least two elastic sensing elements and the bottom of the well (claim 1), wherein the sensing elements are configured to: (a) permit attachment of the three-dimensional ex vivo skeletal muscle tissue (claims 26-27) formed there between (claim 1), thereby suspending the three-dimensional ex vivo skeletal muscle tissue (claims 26-27) above the bottom of the well (claim 1), and (b) deform in response to a contractile force exerted on the sensing elements (claim 1) by the three-dimensional ex vivo skeletal muscle tissue (claims 26-27).
In the analogous art of electrodes for 3D tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the device of claims 1 and 26 of Radisic with the device of claims 1 and 27 of Radisic in order to seed skeletal muscle cells in a hydrogel so that they are capable of contracting the hydrogel in order to sense contraction on the at least two elastic sensing elements to simulate a physiological environment that is native to the tissue and/or permit measurement of the contractile force (Radisic, claim 1).
Radisic does not disclose in its claims:
A hydrogel mixture comprising thrombin.
Regarding feature 1, Bashir discloses:
a hydrogel mixture comprising thrombin (col. 18, lines 8-31).
In the analogous art of muscle-powered biological machines, it would have been obvious to one skilled in the art before the effective filing date to modify Radisic with the thrombin of Bashir in order to cross-link the hydrogel comprising skeletal muscle cells into a stable 3D gel network and compaction of the muscle tissue (Bashir, col. 28, lines 34-37 and col. 49, lines 10-15).
Regarding inherency argument 1, the limitation “the skeletal muscle tissue is characterized by one or more contractions in response to an electrical and/or chemical stimulation”, this property is an inherent property to skeletal muscle tissue, as skeletal muscles contract in response to an electrical and/or chemical stimulation from the nervous system (see pgs. 7-10 of 10 of Betts “10.2: Skeletal Muscle”). Neurons acquire their ability to electrically signal from the ions present (or not present), so the Examiner also considers the electrical stimulation a chemical stimulation. Regarding the limitation “and/or chemical stimulation”, this limitation is claimed in the alternative, so no further rejections are needed at this time. Additionally, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Radisic would be fully capable of operating in this manner given the hydrogel and the skeletal muscle tissue.
Regarding inherency argument 2, the limitation “wherein the three-dimensional ex vivo skeletal muscle tissue does not contract in the absence of electrical and/or chemical stimulation”, skeletal muscle cells do not have the inherent ability to contract on their own (see pg. 7 of 10 of Betts “10.2: Skeletal Muscle”), and require a stimulus (such as an electrical and/or chemical stimulation of independent claim 21, such as a movement of ions across a membrane, usually due to efferent neuronal firing within the human body) (see pg. 7 of 10 of Betts “10.2: Skeletal Muscle”). Additionally, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Radisic would be fully capable of operating in this manner given the hydrogel and the skeletal muscle tissue.
Regarding claim 22, Radisic discloses wherein the bioreactor (claim 1) further comprises at least two electrodes (claim 1) configured to apply an electrical stimulation (claim 1) to the three-dimensional ex vivo skeletal muscle tissue (claims 26-27) of the bioreactor (claim 1).
In the analogous art of electrodes for 3D tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the device of claims 1 and 26 of Radisic with the device of claims 1 and 27 of Radisic in order to seed skeletal muscle cells in a hydrogel so that they are capable of contracting the hydrogel in order to sense contraction on the at least two elastic sensing elements to simulate a physiological environment that is native to the tissue and/or permit measurement of the contractile force (Radisic, claim 1).
Regarding claim 41, Radisic discloses wherein the plurality of cells further comprises fibroblasts (claim 27).
Claim 23 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, and 26-27 of copending Application No. 17/798047 (Radisic), in view of Bashir (US 10906169) as applied to claim 21, further in view of evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 23, Radisic discloses wherein the at least two elastic sensing elements comprise a synthetic polymer (claim 14), a biologic polymer (claims 14 and 16), or a combination thereof (claim 14).
In the analogous art of electrodes for 3D tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the device of claims 1 and 26-27 of Radisic with the device of claim 14 of Radisic in order to sense contraction on the at least two polymeric elastic sensing elements to simulate a physiological environment that is native to the tissue and/or permit measurement of the contractile force (Radisic, claim 1).
Claim 24 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, 16, and 26-27 of copending Application No. 17/798,047 in view of Bashir (US 10906169) as applied to claim 23, further in view of evidentiary reference Betts (“10.2: Skeletal Muscle”) and Miklas (US 20160282338). This is a provisional nonstatutory double patenting rejection.
Regarding claim 24, Radisic discloses wherein the sensing elements comprise a synthetic polymer (claim 14), a biologic polymer (claims 14 and 16 “POMaC”), or a combination thereof (claim 14).
In the analogous art of electrodes for 3D tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the device of claims 1 and 26-27 of Radisic with the device of claims 14 and 16 of Radisic in order to sense contraction on the at least two polymeric elastic sensing elements to simulate a physiological environment that is native to the tissue and/or permit measurement of the contractile force (Radisic, claim 1).
Radisic does not disclose in its claims wherein the polymer is degradable.
Evidentiary reference Miklas discloses wherein the polymer is degradable (paragraph [0176] “composed of the biodegradable polymer … POMaC”).
Claim 25 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, and 26-27 of copending Application No. 17/798,047 in view of Bashir (US 10906169) as applied to claim 23, further in view of Miklas (US 20160282338) and evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection.
Regarding claim 25, Radisic discloses wherein the sensing elements comprise a synthetic polymer (claim 14), a biologic polymer (claim 14), or a combination thereof (claim 14).
Radisic does not disclose in its claims wherein the polymer is nondegradable.
Miklas discloses wherein the polymer is nondegradable (paragraph [0186] “synthetic nonbiodegradable polymers”).
In the analogous art of three-dimensional tissue scaffolds, it would have been obvious to one skilled in the art before the effective filing date to modify the polymer of modified Radisic with the nondegradable polymer of Miklas in order to not have the polymer scaffold break down over time during the cell culture.
Claims 26-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, 16, and 26-27 of copending Application No. 17/798047 (Radisic) in view of Bashir (US 10906169) as applied to claim 21, further in view of evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 26, Radisic discloses wherein each elastic sensing element comprises a polymer selected from the group consisting of: poly(glycerol sebacate) (claim 14) and poly(octamethylene maleate (anhydride) citrate) (POMaC) (claims 14 and 16).
Regarding claim 27, Radisic discloses wherein the polymer comprises POMaC (claims 14 and 16).
In the analogous art of electrodes for 3D tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the device of claims 1 and 26-27 of Radisic with the device of claims 14 and 16 of Radisic in order to sense contraction on the at least two polymeric elastic sensing elements to simulate a physiological environment that is native to the tissue and/or permit measurement of the contractile force (Radisic, claim 1).
Claim 28 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 19, and 26-27 of copending Application No. 17/798047 (Radisic) in view of Bashir (US 10906169) as applied to claim 21, further in view of evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 28, Radisic discloses wherein the at least two elastic sensing elements have an elasticity from about 20 kPa to 0.5 MPa (claim 19). This range is within the claimed range of 10 kPa to 0.8 MPa, so Radisic renders this limitation rejected.
In the analogous art of electrodes for 3D tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the device of claims 1 and 26-27 of Radisic with the device of claim 19 of Radisic in order to sense contraction on the at least two polymeric elastic sensing elements to simulate a physiological environment that is native to the tissue and/or permit measurement of the contractile force (Radisic, claim 1).
Claim 29 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 20, and 26-27 of copending Application No. 17/798047 (Radisic) in view of Bashir (US 10906169) as applied to claim 21, further in view of evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 29, Radisic discloses wherein the at least two elastic sensing elements are in the form of polymer wires (claim 20).
In the analogous art of three-dimensional tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the elastic sensing elements to be polymeric wires in order to sense contraction on the at least two polymeric elastic sensing elements to simulate a physiological environment that is native to the tissue and/or permit measurement of the contractile force (Radisic, claim 1).
Claim 30 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 13, and 26-27 of copending Application No. 17/798047 (Radisic) in view of Bashir (US 10906169) as applied to claim 21, further in view of evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 30, Radisic discloses wherein the bioreactor comprises 2 to 25 elastic sensing elements per well (claim 13).
In the analogous art of three-dimensional tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of modified Radisic with the 2 to 25 sensing elements per well in order to sense contraction on the at least two polymeric elastic sensing elements to simulate a physiological environment that is native to the tissue and/or permit measurement of the contractile force (Radisic, claim 1).
Claims 31-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 26-27 of copending Application No. 17/798047 (Radisic) in view of Bashir (US 10906169) as applied to claim 21, further in view of evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 31, Radisic discloses wherein the bioreactor comprises a multi-well plate (claim 2).
In the analogous art of three-dimensional tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the well of modified Radisic to have multiple wells in order to parallelize and perform a plurality of tissue cultures under varying electrical and/or chemical conditions if needed.
Regarding claim 32, Radisic discloses wherein the multi-well plate comprises 6 wells, 12 wells, 24 wells, or 96 wells (claim 2).
Regarding the limitation “8 wells, … 384 wells, or 1536 wells” this limitation is claimed in the alternative. No further rejections are required at this time.
In the analogous art of three-dimensional tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the well of modified Radisic to have multiple wells in order to parallelize and perform a plurality of tissue cultures under varying electrical and/or chemical conditions if needed.
Claim 42 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 26-27 of copending Application No. 17/798047 (Radisic) in view of Bashir (US 10906169) as applied to claim 41, further in view of Lancaster (US 20210290823), further in view of evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 42, Radisic does not disclose wherein the fibroblasts and the skeletal muscle tissue are at a ratio of between about 1:5 and 1:50.
Lancaster discloses wherein the fibroblasts and the skeletal muscle tissue are at a ratio of between about 1:5 and 1:50 (paragraph [0008]).
In the analogous art of muscle cell patches, it would have been obvious to one skilled in the art before the effective filing date to modify modified Radisic with the ratio of fibroblasts and skeletal muscle tissue of Lancaster in order to provide a scaffold that is capable of spontaneous synchronized contractions across the surface of the scaffold (Lancaster, paragraph [0008]).
Claims 44-45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 11, and 26-27 of copending Application No. 17/798047 (Radisic) in view of Bashir (US 10906169) as applied to claim 21, further in view of evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 44, Radisic discloses wherein the three-dimensional ex vivo skeletal muscle tissue is produced using a stimulation protocol (claim 11).
Radisic does not disclose wherein the three-dimensional ex vivo skeletal muscle tissue is produced using a stimulation protocol comprising a plurality of pulses separated by no electrical stimulations, wherein each pulse is at least about 10 Hz applied for a duration of about one second.
In the analogous art of electrodes for 3D tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the device of claims 1-2 and 26-27 of Radisic with the device of claim 11 of Radisic in order to seed skeletal muscle cells in a hydrogel so that they are capable of contracting the hydrogel in order to sense contraction on the at least two elastic sensing elements to simulate a physiological environment that is native to the tissue and/or permit measurement of the contractile force (Radisic, claim 1).
Regarding the limitation, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Radisic would be fully capable of operating in this manner given the hydrogel and the skeletal muscle tissue. Also see MPEP 2113 (Product-by-Process Claims).
Regarding claim 45, Radisic discloses the three-dimensional ex vivo skeletal muscle tissue is produced using a stimulation protocol (claim 11).
Radisic does not disclose the three-dimensional ex vivo skeletal muscle tissue is produced using a stimulation protocol comprising applying a first frequency for a first duration and a second frequency for a second duration, wherein the first frequency is increased to the second frequency at a ramp rate which is at least about 0.1 Hz/hour.
Regarding the limitation, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Radisic would be fully capable of operating in this manner given the hydrogel and the skeletal muscle tissue. Also see MPEP 2113 (Product-by-Process Claims).
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned 17/798047, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
Claims 21-22, 41, and 44-45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 30 of copending Application No. 17/798048 (Aschar-Sobbi) in view of Bashir (US 10906169), further in view of evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 21, Aschar-Sobbi discloses a tissue system (claim 1) comprising a three-dimensional (claim 1) ex vivo skeletal muscle tissue (claims 1 and 30) and a bioreactor (claim 1), wherein the three-dimensional (claim 1) ex vivo skeletal muscle tissue (claims 1 and 30) comprises a hydrogel (claim 30) and a plurality of cells that includes skeletal muscle cells (claim 30), wherein at least a portion of the cells are encapsulated inside the hydrogel (claim 30), wherein the skeletal muscle tissue (claims 1 and 30) is characterized by one or more contractions in response to an electrical stimulation (claim 1; and see inherency argument 1, below), wherein the three-dimensional ex vivo skeletal muscle tissue does not contract in the absence of electrical and/or chemical stimulation (see inherency argument 2, below) and wherein the bioreactor comprises:
a device having a well (claim 1) configured for growing the three-dimensional (claim 1) ex vivo skeletal muscle tissue (claims 1 and 30) from the cells seeded therein (claim 1), wherein the well has a bottom (claim 1); and
at least two elastic sensing elements (claim 1) disposed across the well such that there is a gap between the at least two elastic sensing elements and the bottom of the well (claim 1), wherein the sensing elements are configured to: (a) permit attachment of the three-dimensional ex vivo skeletal muscle tissue (claims 1 and 30) formed there between, thereby suspending the three-dimensional ex vivo skeletal muscle tissue (claims 1 and 30) above the bottom of the well (claim 1), and (b) deform in response to a contractile force exerted on the sensing elements (claim 1) by the three-dimensional ex vivo skeletal muscle tissue (claims 1 and 30).
Aschar-Sobbi does not disclose in the claims:
a hydrogel mixture comprising thrombin.
Regarding feature 1, Bashir discloses:
a hydrogel mixture comprising thrombin (col. 18, lines 8-31).
In the analogous art of muscle-powered biological machines, it would have been obvious to one skilled in the art before the effective filing date to modify Aschar-Sobbi with the thrombin of Bashir in order to cross-link the hydrogel comprising skeletal muscle cells into a stable 3D gel network and compaction of the muscle tissue (Bashir, col. 28, lines 34-37 and col. 49, lines 10-15).
Regarding inherency argument 1, the limitation “the skeletal muscle tissue is characterized by one or more contractions in response to an electrical and/or chemical stimulation”, this property is an inherent property to skeletal muscle tissue, as skeletal muscles contract in response to an electrical and/or chemical stimulation from the nervous system (see pgs. 7-10 of 10 of Betts “10.2: Skeletal Muscle”). Neurons acquire their ability to electrically signal from the ions present (or not present), so the Examiner also considers the electrical stimulation a chemical stimulation. Regarding the limitation “and/or chemical stimulation”, this limitation is claimed in the alternative, so no further rejections are needed at this time. Additionally, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Aschar-Sobbi would be fully capable of operating in this manner given the hydrogel and the skeletal muscle tissue.
Regarding inherency argument 2, the limitation “wherein the three-dimensional ex vivo skeletal muscle tissue does not contract in the absence of electrical and/or chemical stimulation”, skeletal muscle cells do not have the inherent ability to contract on their own (see pg. 7 of 10 of Betts “10.2: Skeletal Muscle”), and require a stimulus (such as an electrical and/or chemical stimulation of independent claim 21, such as a movement of ions across a membrane, usually due to efferent neuronal firing within the human body) (see pg. 7 of 10 of Betts “10.2: Skeletal Muscle”). Additionally, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Aschar-Sobbi would be fully capable of operating in this manner given the hydrogel and the skeletal muscle tissue.
Regarding claim 22, Aschar-Sobbi discloses wherein the bioreactor further comprises at least two electrodes (claim 1) configured to apply an electrical stimulation (claim 1) to the three-dimensional ex vivo skeletal muscle tissue (claims 1 and 30) of the bioreactor (claim 1).
Regarding claim 41, Aschar-Sobbi discloses wherein the plurality of cells further comprises fibroblasts (claim 30).
Regarding claim 44, Aschar-Sobbi discloses wherein the three-dimensional ex vivo skeletal muscle tissue is produced using a stimulation protocol (claim 1).
Aschar-Sobbi does not disclose wherein the three-dimensional ex vivo skeletal muscle tissue is produced using a stimulation protocol comprising a plurality of pulses separated by no electrical stimulations, wherein each pulse is at least about 10 Hz applied for a duration of about one second.
Regarding the limitation, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Aschar-Sobbi would be fully capable of operating in this manner given the hydrogel and the skeletal muscle tissue. Also see MPEP 2113 (Product-by-Process Claims).
Regarding claim 45, Aschar-Sobbi discloses the three-dimensional ex vivo skeletal muscle tissue is produced using a stimulation protocol (claim 1).
Aschar-Sobbi does not disclose the three-dimensional ex vivo skeletal muscle tissue is produced using a stimulation protocol comprising applying a first frequency for a first duration and a second frequency for a second duration, wherein the first frequency is increased to the second frequency at a ramp rate which is at least about 0.1 Hz/hour.
Regarding the limitation, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Aschar-Sobbi would be fully capable of operating in this manner given the hydrogel and the skeletal muscle tissue. Also see MPEP 2113 (Product-by-Process Claims).
Claims 23 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 18, and 30 of copending Application No. 17/798048 (Aschar-Sobbi) in view of Bashir (US 10906169) as applied to claim 21, further in view of evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 23, Aschar-Sobbi discloses wherein the at least two sensing elements comprise a synthetic polymer (claim 18), a biologic polymer (claim 18), or a combination thereof (claim 18).
In the analogous art of 3D tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the 3D tissue culture system of Aschar-Sobbi with the polymer of claim 18 in order to produce a sensing element that is capable of deforming in response to a contractile force exerted on the sensing elements by the three-dimensional tissue (Aschar-Sobbi, claim 1).
Claim 24 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 18, and 30 of copending Application No. 17/798048 (Aschar-Sobbi) in view of Bashir (US 10906169) as applied to claim 23, in view of evidentiary references Miklas (US 20160282338) and Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 24, Aschar-Sobbi discloses wherein the sensing elements comprise a synthetic polymer (claim 18), a biologic polymer (claim 18), or a combination thereof (claim 18).
Aschar-Sobbi does not disclose wherein the polymer is degradable.
Evidentiary reference Miklas discloses wherein the polymer is degradable (paragraph [0176] “POMaC” is biodegradable).
Claim 25 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 18, and 30 of copending Application No. 17/798048 (Aschar-Sobbi) in view of Bashir (US 10906169) as applied to claim 23, in view of Miklas (US 20160282338), further in view of evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 25, Aschar-Sobbi does not disclose wherein the polymer is nondegradable.
Miklas discloses wherein the polymer is nondegradable (paragraph [0186]).
In the analogous art of 3D tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the polymer of modified Aschar-Sobbi to be nondegradable as in Miklas in order to not have the polymer scaffold break down over time during the cell culture.
Claims 26-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 18, 20, and 30 of copending Application No. 17/798048 (Aschar-Sobbi) in view of Bashir (US 10906169) as applied to claim 21, further in view of evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 26, Aschar-Sobbi discloses wherein each elastic sensing element comprises a polymer selected from the group consisting of: poly(glycerol sebacate) (claim 18) and poly(octamethylene maleate (anhydride) citrate) (POMaC) (claims 18 and 20).
In the analogous art of 3D tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the 3D tissue culture system of Aschar-Sobbi with the polymers of claims 18 and/or 20 in order to produce a sensing element that is capable of deforming in response to a contractile force exerted on the sensing elements by the three-dimensional tissue (Aschar-Sobbi, claim 1).
Regarding the remainder of the claim, the remainder was not elected.
Regarding claim 27, Aschar-Sobbi discloses wherein the polymer comprises POMaC (claims 18 and 20).
In the analogous art of 3D tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the 3D tissue culture system of Aschar-Sobbi with the polymers of claims 18 and/or 20 in order to produce a sensing element that is capable of deforming in response to a contractile force exerted on the sensing elements by the three-dimensional tissue (Aschar-Sobbi, claim 1).
Claims 28-29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 23, and 30 of copending Application No. 17/798048 (Aschar-Sobbi) in view of Bashir (US 10906169) as applied to claim 21, further in view of evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 28, Aschar-Sobbi discloses wherein the at least two elastic sensing elements have an elasticity from about 20 kPa to 0.5 MPa (claim 23). This range is within the claimed range of 10 kPa to 0.8 MPa, so Aschar-Sobbi renders this limitation rejected.
In the analogous art of 3D tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the 3D tissue culture system of Aschar-Sobbi with the sensing elements of claim 23 in order to produce a sensing element that is capable of deforming in response to a contractile force exerted on the sensing elements by the three-dimensional tissue (Aschar-Sobbi, claim 1).
Regarding claim 29, Aschar-Sobbi discloses wherein the at least two elastic sensing elements are in the form of polymer wires (claim 23).
In the analogous art of 3D tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the 3D tissue culture system of Aschar-Sobbi with the polymer wire sensing elements of claim 23 in order to produce a sensing element that is capable of deforming in response to a contractile force exerted on the sensing elements by the three-dimensional tissue (Aschar-Sobbi, claim 1).
Claims 30-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, and 30 of copending Application No. 17/798048 (Aschar-Sobbi) in view of Bashir (US 10906169) as applied to claim 21, further in view of evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 30, Aschar-Sobbi discloses wherein the bioreactor comprises 2 to 25 elastic sensing elements per well (claim 7).
In the analogous art of three-dimensional tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of modified Aschar-Sobbi with the 2 to 25 sensing elements per well in order to sense contraction on the at least two elastic sensing elements to simulate a physiological environment that is native to the tissue and/or permit measurement of the contractile force (Aschar-Sobbi, claim 1).
Regarding claim 31, Aschar-Sobbi discloses wherein the bioreactor comprises a multi-well plate (claim 7).
In the analogous art of three-dimensional tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of modified Aschar-Sobbi with the multi-well plate in order to have multiple wells in order to parallelize and perform a plurality of tissue cultures under varying electrical and/or chemical conditions if needed.
Regarding claim 32, Aschar-Sobbi discloses wherein the multi-well plate comprises 6 wells, 12 wells, 24 wells, or 96 wells (claim 7).
In the analogous art of three-dimensional tissue culture, it would have been obvious to one skilled in the art before the effective filing date to modify the bioreactor of modified Aschar-Sobbi with the multi-well plate in order to have multiple wells in order to parallelize and perform a plurality of tissue cultures under varying electrical and/or chemical conditions if needed.
Regarding the limitation “8 wells, … 384 wells, or 1536 wells”, this limitation is claimed in the alternative. No further rejections are required at this time.
Claim 42 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 30 of copending Application No. 17/798048 (Aschar-Sobbi) in view of Bashir (US 10906169) as applied to claim 41, further in view of Lancaster (US 20210290823) and evidentiary reference Betts (“10.2: Skeletal Muscle”). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 42, Aschar-Sobbi does not disclose wherein the fibroblasts and the skeletal muscle tissue are at a ratio of between about 1:5 and 1:50.
Lancaster discloses wherein the fibroblasts and the skeletal muscle tissue are at a ratio of between about 1:5 and 1:50 (paragraph [0008]).
In the analogous art of muscle cell patches, it would have been obvious to one skilled in the art before the effective filing date to modify modified Radisic with the ratio of fibroblasts and skeletal muscle tissue of Lancaster in order to provide a scaffold that is capable of spontaneous synchronized contractions across the surface of the scaffold (Lancaster, paragraph [0008]). Additionally, the contractile construct can be implanted in a subject in need thereof after culturing. The construct may be implanted prior to onset of cellular contraction and/or patch level contraction (Lancaster, paragraph [0007]).
Additional Prior Art References
The prior art made of record and not relied upon is considered pertinent to Applicant’s disclosure.
Betts (“10.7: Cardiac Muscle Tissue”) – This non-patent literature describes cardiac muscle tissue, see Response to Arguments.
Hinds (“The role of extracellular matrix composition in structure and function of bioengineered skeletal muscle”) – This non-patent literature describes a two-point attachment to a cultured muscle bundle.
Nunes (“Biowire: a platform for maturation of human pluripotent stem cell–derived cardiomyocytes”) – This non-patent literature describes a biowire upon which cardiomyocytes are cultured.
Nunes (“Supplementary Figure 1”) – This non-patent literature is a supplementary figure depicting the biowire setup to the non-patent literature of Nunes (“Biowire: a platform for maturation of human pluripotent stem cell–derived cardiomyocytes”), cited above.
Response to Arguments
Applicant’s arguments filed October 10, 2025 have been fully considered but they are not persuasive.
Regarding Applicant arguments about claim 21, the independent claim now incorporates the claim limitations of previous claim 43, now cancelled.
However, due to the previously stated reasons, claim 43’s incorporation into the independent claim 21 is still obvious. Additionally, skeletal muscle cells do not have the inherent ability to contract on their own (see pg. 7 of 10 of Betts “10.2: Skeletal Muscle”), and require a stimulus (such as an electrical and/or chemical stimulation of independent claim 21, such as a movement of ions across a membrane, usually due to efferent neuronal firing within the human body) (see pg. 7 of 10 of Betts “10.2: Skeletal Muscle”).
Furthermore, the type of cell being used in the system is another form of intended use and manner of operation. Regarding the limitation “skeletal muscle tissue”, the material or article worked upon by the apparatus does not limit the apparatus claims. MPEP § 2115. This limitation is a manner of operating or intended use of a claimed apparatus and does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Miklas in view of Bashir would be fully capable of operating in this manner given the structures such as a well and the at least two elastic sensing elements with a gap to the bottom of the well. Similar arguments can be made for the non-statutory double patenting rejection under modified Aschar-Sobbi.
Regarding arguments about the nature of ex vivo and in vitro experimentation, Miklas discloses at paragraph [0177]:
In still other aspects, the disclosed bioreactor systems may be similar to or reproduce the complexity of the native tissue architecture in vitro, thus enabling the cultivated cells to assume the structure which they would be expected to assume in vivo. Reproducing this structure may enable the cells to mature and to assume a similar function they would have in vivo.
Regarding Bashir, this reference is only used to provide for the thrombin in the hydrogel, and not the structure of the 3D-printed ring mold. All arguments to latter are moot. For motivation in favor of combining thrombin in the hydrogel:
In the analogous art of muscle-powered biological machines, it would have been obvious to one skilled in the art before the effective filing date to modify Miklas with the thrombin of Bashir in order to cross-link the hydrogel comprising skeletal muscle cells into a stable 3D gel network and compaction of the muscle tissue (Bashir, col. 28, lines 34-37 and col. 49, lines 10-15).
Even when combined with dependent claim 42, wherein the spontaneous contraction of muscle cell patches occur (as seen in Lancaster, paragraph [0008]), Lancaster provides support for this contraction only at the specified ratio of fibroblasts and the skeletal muscle tissue in its entire muscle patch (see Lancaster, paragraphs [0008]-[0009] “the construct is capable of spontaneous synchronized contractions across the surface” and “contacting a patient with a contractile cell-based disorder with an amount effective to treat the disorder with the construct”). Additionally, in Lancaster, the cells were spontaneously contracting because of Lancaster’s invention is used with cardiac muscle cells. It is well-known that muscles of the heart display different structural features and functioning in the field; one such functioning is the ability of cardiac muscle cells to spontaneously beat on their own (see pg. 1 of 2 of Betts “10.7: Cardiac Muscle Tissue” in the Additional Prior Art section above). However, the combined prior art references only cite skeletal muscle cells, which do not display this inherent property, see above. Additionally, skeletal muscle cells can be used in Lancaster’s device (paragraph [0007]).
Regarding the non-statutory double patenting rejections, the following MPEP section has been described as in the previous rejection:
(i) Application under examination has the earlier patent term filing date
If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent.
-- MPEP § 804(I)(B)(1)(b)(i)
As the non-statutory double patenting rejections are not the only rejection remaining in the instant application, the Examiner is keeping the non-statutory double rejections at this point in time.
Conclusion
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/N.G.E./Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799