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 .
Applicant's election without traverse of Group I, claims 1-16, in the reply filed on 1 April 2026 is acknowledged. Claims 17-20 have been withdrawn. Claims 1-16 are currently pending and under examination.
This Application is a national phase application under 35 U.S.C. §371 of International Application No. PCT/US2021/045813, filed 12 August 2021, which claims priority to U.S. Provisional Application No. 63/065694, filed 14 August 2020.
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 1-16 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 1 recites in relevant part that the number of microcompartments is determined “based at least in part” on a size of the implantable assay array, and the size of the array is determined “based at least in part” on a size of the implantation subject. These limitations are indefinite, because it is unclear what other determinations are intended to be included in, or excluded from, the determination of array size and microcompartment number, in addition to the size of the array and size of the subject. Further, it is unclear what “part” (e.g. what percentage) is required to be considered based “in part” on the noted conditions.
Claim 5 recites the limitation "the cells or microtissues" in line 2. There is insufficient antecedent basis for this limitation in the claim. No cells or microtissues are present in claim 1, from which this claim depends.
Claim 6 recites:
wherein a microcompartment of the microcompartments comprises a hydrogel formulation, and wherein the hydrogel formulation comprises gelatin methacryloyl (GelMA) having a weight percent of about 1% to about 50%, poly(ethylene glycol) diacrylate (PEGDA) having a weight percent of about 1% to about 20%, fibrin, collagen, Matrigel, and cell media, or combinations thereof (emphasis added).
This claim is indefinite, because as currently recited, it is unclear if all of the recited components are required to be present, as suggested by “and”; or instead, if only one recited component is required to be present, as suggested by “or combinations thereof.”
Claims 9 and 12 are likewise indefinite due to the recitation of “and” and “or combinations thereof.”
Claim 10 recites the limitation "the crosslinked hydrogel" in line 3. There is insufficient antecedent basis for this limitation in the claim. No crosslinked hydrogel is present in claim 1, from which this claim depends.
Claim 11 recites the limitation "the cover" in line 1. There is insufficient antecedent basis for this limitation in the claim. No cover is present in claim 1, from which this claim depends.
Further regarding claim 11, this claim indicates that the cover transmits at least a portion “of electromagnetic radiation generated by luciferase.” This limitation is indefinite, because no luciferase is recited as being present. As such, it is unclear if luciferase, and/or electromagnetic radiation are intended to be present within the implantable assay array.
Claims 2-4, 7, 8, and 13-16, are included in this rejection, as these claims depend from above rejected claims and fails to remedy the noted deficiencies.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-3, 10, and 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Santini et al. (IDS; US 2008/0076975; Published 2008).
With regard to claims 1-3, Santini et al. teach an implantable assay array comprising a biocompatible substrate comprising a number of mutually isolated reservoirs, which are microcompartments (Abs.; Fig. 1-3). The array is implantable into non-human animals including mice and rats (Para. 74), and the array includes a plurality of microcompartments, including two (Fig. 3).
As Santini et al. expressly teach that the non-human animal the array is implantable into includes mice and rats, and that the array can include two microcompartments, it would have been obvious to one of ordinary skill in the art to utilize a mouse or a rat, where the biocompatible substrate include two microcompartments, which is fully encompassed within 2 to about 500, and 2 to about 50,000 microcompartments.
Further, as the array is intended to be implanted into specific animal subjects (see Para. 74), it would have been obvious to one of ordinary skill in the art that the array, which includes the microcompartments, must necessarily fit within the body of the animal subject. Thus, an ordinary artisan would have been motivated to base the size of the array, including its number of microcompartments, on the size of the animal intended to receive the array via implantation.
With regard to claim 10, Santini et al. teach that the array further comprises a reservoir cap overlaying the reservoirs (Fig. 2), which is a cover overlying the microcompartments, and capable of enclosing the contents of the microcompartments, including capable of overlying a crosslinked hydrogel within the microcompartments.
With regard to claim 13, Santini et al. teach that the array is intended to be implanted into an animal for therapeutic and/or pre-clinical testing purposes (Para. 97). It can be seen that the implanted array has edges (see Figs. 1A-1C), wherein the edges are one or more apertures capable of permitting suturing upon implantation into the implantation subject.
With regard to claim 14, Santini et al. teach that the array further comprises a substrate portion/backplate, which is a backing surface, where the biocompatible substrate comprising the microcompartments is dispose on the backing surface (Fig. 2).
With regard to claim 15, Santini et al. teach that the body portion and reservoirs, which is the biocompatible substrate, is made of material that is impermeable to the contents of the reservoirs and to the surrounding environment (Para. 72). Thus, the biocompatible substrate is substantially impermeable to cells, extracellular matrix, and biological molecules, and each microcompartment is a biologically isolated environment.
With regard to claim 16, Santini et al. teach that the microcompartments have a volume that includes greater than about 1µl and less than 500 µl, or greater than 500 µl and less than 1 mL (Para. 74), which are ranges fully encompassed within about 0.1 µl to about 1000 µl.
Claims 1, 4, and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Santini et al., as applied to claim 1 above, and further in view of Shepherd et al. (IDS; US 2020/0181580; Published June 11, 2020).
The teachings of Santini et al. as applied to claim 1 have been set forth above.
With regard to claims 4 and 5, Santini et al. further teach that the microcompartment contents can include essentially any natural or synthetic, organic or inorganic molecule or mixture thereof, for release (Para. 36), including therapeutic, prophylactic, or diagnostic agents (Para. 37). However, it is not specifically taught that a cell or microtissue, including hepatocytes, endothelial cells, stromal cells, or combinations thereof, are disposed in the microcompartments.
Shepherd et al. teach implantable liver tissue constructs for use in the augmentation or restoration of liver functions by in vivo delivery of liver tissue, the constructs including mammalian hepatocytes and endothelial cells (Abs.; para. 109).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Santini et al. with Shepherd et al., because both teach implantable constructs that include therapeutic agents. The implantation of a construct including liver tissue and cells into a subject is known in the art as taught by Shepherd et al. The inclusion of liver tissue, hepatocytes, and/or endothelial cells as a therapeutic agent in the microcompartments of Santini et al. amounts to the simple substitution of one known therapeutic agent for another, and would have been expected to predictably and successfully provide an alternative agent usable for the restoration of liver function by in vivo delivery of the liver tissue/cells.
Claims 1, 6-9, 11, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Santini et al., as applied to claim 1 above, and further in view of Shawgo et al. (US 6,730,072; Published 2004).
The teachings of Santini et al. as applied to claim 1 have been set forth above.
With regard to claims 6, 7, 9, and 12, Santini et al. further teach that the arrays and their components can be made using methods known in the art including from U.S. Pat. No. 6,730,072 (Shawgo et al.). However, the specific teachings of Shawgo et al. are not expressly recited.
Shawgo et al. teach methods and devices for mechanically sealing the reservoirs of microchip devices to prevent leakage from or between any of the reservoirs (Abs.). The device may include a hydrogel, and materials utilized to make the device include polymers and cross-linked materials, including collagen (Col. 4, line 31-41; Col. 5, line 30-41; Col. 6, line 51-63).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Shawgo et al. with Santini et al., because Santini et al. expressly indicate that the teachings of Shawgo et al. can be utilized for providing the array. Shawgo et al. teach that the device, which includes a substrate having sealed reservoirs, includes a hydrogel formulation comprising cross-linked materials including collagen. As collagen is a preferred material used in the instant cross-linked hydrogel (see claim 6), the hydrogel formulation taught by Shawgo et al. is crosslinked and characterized by a compressive modulus from about 75Pa to about 10kPa. Further, as Santini et al. teach the use of the methods and materials of Shawgo et al., an ordinary artisan would have been motivated to follow the express direction of Santini et al. and provide a hydrogel formulation including collagen to provide components of the array, including the overall biocompatible substrate, its microcompartments, biological scaffold matrix, which is the interior of the microcompartments, and its cover, as taught by the incorporated Shawgo et al. The use of the materials as taught by Shawgo et al. would have been expected to predictably and successfully provide the array as desired by Santini et al.
With regard to claim 8, taken together Santini et al. and Shawgo et al. teach the array as claimed, including the materials as claimed. As the array and materials cannot be separated from their properties, the hydrogel formulation would necessarily comprise a nodule, which Applicant defines as a region of nonuniform properties (see Spec., p. 14).
With regard to claim 11, Santini et al. teach that the array further comprises a reservoir cap overlaying the reservoirs (Fig. 2), which is a cover overlying the microcompartments, and capable of enclosing the contents of the microcompartments, including capable of overlying a crosslinked hydrogel within the microcompartments. Further, as Santini et al. teach a cover as claimed, the cover as taught is necessary capable of transmitting at least a portion of electromagnetic radiation generated by luciferase.
Conclusion
No claims are allowable.
Art of Record:
Keller et al., U.S. 5,893,974; Published 1999 (capsule for transplantation containing an immunologically isolated cell, the capsule made of a biologically compatible material having spaced pores large enough to let a desired biologically active molecular product through, while blocking the passage of all larger immunological molecules).
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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
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