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 .
Status of the Claims
This action is in response to the communication of 5/15/2023
Claims 1-9 are pending.
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 1-9 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, the term “scaffold” is not defined in the specification, and it is unclear what exactly the metes and bounds of a scaffold as claimed would be.
The meaning of every term used in a claim should be apparent from the prior art or from the specification and drawings at the time the application is filed. Claim language may not be “ambiguous, vague, incoherent, opaque, or otherwise unclear in describing and defining the claimed invention.” In re Packard, 751 F.3d 1307, 1311, 110 USPQ2d 1785, 1787 (Fed. Cir. 2014). (MPEP 2173.05(a)). The term scaffold appears to refer to either a hydrogel [0007], but in other sections of the specification the decellularized tissue/ KEM itself is referred to as a “scaffold” instead of the scaffold “using” KEM. (Spec. [0016, 0022]). If that were the case, and the “scaffold” is intended to mean KEM itself, then the claim scope would include any composition comprising KEM, which would be essentially a product of nature, i.e., any living thing possessing kidneys.
The specification does state in paragraph [0007] that “The present disclosure is conceived to obtain a large amount of decellularized tissue through a chemical treatment of a porcine kidney tissue, prepare a hydrogel scaffold based on the decellularized tissue and apply it to kidney organoid culture.”
For purposes of examination, the broadest reasonable interpretation from the specification and figures appears of the term “scaffold” as claimed appears to mean any composition, ideally but not necessarily a hydrogel, that further comprises kidney extracellular matrix as a component of said composition. Technically, as written, claim 1 encompasses any naturally occurring kidney.
Claim 1 also includes an intended use clause, which makes the scope of claim 1 indefinite because it is unclear if this claim is directed to a method of using the claimed scaffold for cell culture, or is claim 1 directed to the scaffold itself? In other words, claim 1 is a product claim that recites a method (a use), which is indefinite because of improperly mixing statutory classes.
For purposes of examination, claim 1 is interpreted as a product claim, and the recited intended use of the product technically is not considered limiting on the claimed scaffold/ hydrogel scaffold itself. That is, the scope of claim 1 is interpreted to include essentially any composition comprising KEM.
Claims 2 and 4 contain the trademark/trade name Triton X-100. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the detergent used for decellularization of kidney tissue, and, accordingly, the identification/description is indefinite.
Claims 8 and 9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: all steps. No steps are positively recited in these method claims; thus, they are indefinite. Claims 2-3 and 5-9 are rejected for being dependent on an indefinite claim.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 1-3 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claim(s) recite(s) “A scaffold…using a kidney extracellular matrix (KEM)”, which is effectively directed to any composition comprising KEM, including KEM itself, which is a naturally occuring extracellular matrix. Thus claim 1 is directed to any naturally occuring KEM, or any naturally occuring kidney, which are products of nature. (MPEP 2106.04(b)(I)). For claims 2-3, these claims only describe steps to isolate KEM, but these claims are still only directed to the naturally-occuring KEM product, in other words these are product-by-process steps.
This judicial exception is not integrated into a practical application because the recited intended use does not change the scope of the claimed natural product. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is directed to a naturally-occuring composition.
Claim Rejections - 35 USC § 102
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 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.
Sullivan
Claims 1, 2 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Sullivan DC, Mirmalek-Sani SH, Deegan DB, Baptista PM, Aboushwareb T, Atala A, Yoo JJ. Decellularization methods of porcine kidneys for whole organ engineering using a high-throughput system. Biomaterials. 2012 Nov;33(31):7756-64.
Regarding claim interpretation, A Kidney Extracellular matrix (KEM) is interpreted to mean a decellularized kidney tissue-derived scaffold for kidney organoid culture. (Spec. [0022]).
Regarding claim 1 and 8, Sullivan teaches decellularization of kidney tissue to generate whole kidney scaffolds (i.e. a KEM). (Sullivan sections 2.2 and 2.3). Sullivan teaches that these scaffolds may be seeded with kidney cells/organoids for the purpose of culture (Sullivan section 2.7). Sullivan teaches that these scaffolds may eventually be used to prepare a tissue-engineered kidney for transplantation, i.e. suggesting that this is a potential use for their scaffold (Sullivan section 5).
Regarding claim 2, Sullivan used a solution comprising 1% Triton X-100/0.1% Ammonium Hydroxide to decellularize kidney tissue (Sullivan, Section 2.2, Fig. 2).
Nagao
Claims 1, 3 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Nagao, Ryan J et al. “Decellularized Human Kidney Cortex Hydrogels Enhance Kidney Microvascular Endothelial Cell Maturation and Quiescence.” Tissue engineering. Part A vol. 22,19-20 (2016): 1140-1150.
Regarding claim 1 and 8, Nagao teaches methods to recreate the human kidney extracellular matrix (kECM) microenvironment by fabricating kECM hydrogels derived from decellularized human kidney cortex (i.e., the claimed scaffold using a KEM). Nagao found that human kidney peritubular microvascular endothelial cells (HKMECs) became more quiescent when cultured on this kECM gel. (Nagao, Abstract). (i.e., using the KEM as part of a hydrogel scaffold for the culture of a kidney organoid).
Regarding claim 3, Nagao teaches the concentration of kECM in their hydrogel scaffold was 7.5 mg/mL. (Fig 3 C.2, Fig. 4 A.2, A.5).
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.
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.
Nagao and Sullivan
Claims 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over:
Nagao, Ryan J et al. “Decellularized Human Kidney Cortex Hydrogels Enhance Kidney Microvascular Endothelial Cell Maturation and Quiescence.” Tissue engineering. Part A vol. 22,19-20 (2016): 1140-1150, and
Sullivan DC, Mirmalek-Sani SH, Deegan DB, Baptista PM, Aboushwareb T, Atala A, Yoo JJ. Decellularization methods of porcine kidneys for whole organ engineering using a high-throughput system. Biomaterials. 2012 Nov;33(31):7756-64.
Claims 1, 2, and 8 are rejected under 35 U.S.C. 102(a)(1) in view of Sullivan.
Claims 1, 3 and 8 are rejected under 35 U.S.C. 102(a)(1) in view of Nagao.
Regarding claim 4, Nagao teaches methods to recreate the human kidney extracellular matrix (kECM) microenvironment by fabricating kECM hydrogels derived from decellularized human kidney cortex (i.e., the claimed scaffold using a KEM). Nagao found that human kidney peritubular microvascular endothelial cells (HKMECs) became more quiescent when cultured on this kECM gel. (Nagao, Abstract). (i.e., using the KEM as part of a hydrogel scaffold for the culture of a kidney organoid).
Nagao teaches that to decellularize human kidneys, the kidneys were diced into 1x1x1 mm pieces prior to being introduced to a decellularization solution (SDS) for 5 days to produce decellularized kidneys (decellularized KCM). (Nagao pg 1143 Results – Decellularization of human kidneys section).
Regarding the claimed “crushed” limitation, Nagao teaches that the kidneys were “diced into 1x1x1mm”. The specification doesn’t give a specific definition for “crushed”, mentioning instead that “The isolated kidney tissue may be crushed by a known method”. (Spec [0054]). However, the specification does specify that in an embodiment the kidney tissue was “finely cut and then decellularized” (Spec. [0072, 0073]). This difference in mechanical action appears to essentially result in the same product, i.e. mechanically broken-down kidney tissue. So, simply for the purposes of examination, the term “crushed” in the claim is considered to read on kidney tissue that had undergone similar mechanical manipulation like mashed, sliced, smashed, diced, etc. because these processes essentially would result in the same “crushed” intermediate mechanically manipulated kidney tissue product.
Nagao does not teach that that the decellularization solution is Triton X-100 and ammonium hydroxide.
Sullivan teaches the decellularization of kidneys using a solution comprising 1% Triton X-100/0.1% Ammonium Hydroxide to decellularize kidney tissue (Sullivan, Section 2.2, Fig. 2). Sullivan teaches decellularization of kidney tissue to generate whole kidney scaffolds (i.e. a KEM). (Sullivan sections 2.2 and 2.3). Sullivan teaches that these scaffolds may be seeded with kidney cells/organoids for the purpose of culture (Sullivan section 2.7). Sullivan teaches that these scaffolds may eventually be used to prepare a tissue-engineered kidney for transplantation, i.e. suggesting that this is a potential use for their scaffold (Sullivan section 5). Sullivan used a solution comprising 1% Triton X-100/0.1% Ammonium Hydroxide to decellularize kidney tissue (Sullivan, Section 2.2, Fig. 2).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to use Sullivan’s kidney decellularization method comprising the use of 1% Triton X-100/0.1% Ammonium Hydroxide to decellularize the kidney tissue of Nagao’s method.
One of ordinary skill in the art would have been motivated to do so, since this combination would be combining prior art elements according to known methods to yield predictable results. (MPEP 2143 (I)(A)). Sullivan teaches a known successful method to decellularize kidney tissue to produce ECM scaffolds, and the result of using this method instead of Nagao’s decellularization would have predicably resulted in the same product, decellularized kidney tissue. Thus, this combination is using a known method (decellularization with Triton-X and ammonium hydroxide) to give a predicable result (decellularized kidney ECM useful for kidney culture scaffolds).
One of ordinary skill in the art would have had a reasonable expectation of success, since Sullivan teaches that their decellularization method decellularizes kidney tissue.
Regarding claim 5, Nagao teaches lyophilizing the decellularized ECM. (Nagao pg. 1141 “Decellularization of human kidney” section.)
Regarding claim 6 and 7, Nagao teaches that the lyophilized kECM was dissolved in a pepsin solution to form a hydrogel. (Nagao pg. 1142 “Gelation of decellularized human kECM and collagen-I” section.). Regarding the adjustment of pH, Nagao teaches that “neutralizing dilutants” were added after the addition of 0.1% acetic acid, which appears to be for the adjustment of pH of the solution to form a hydrogel.
Regarding claim 9, Nagao teaches culturing HKEMC (kidney cells) on their hydrogel, including in a 3D system incorporating their hydrogel to encourage differentiation. Nagao observed that the incorporation of kECM provided a matrix microenvironment, which allowed HKMECs to adopt a phenotype closer to the human kidney. (Nagao, pg. 1148, first full para.).
Conclusion
Claims 1-9 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THOMAS RUSSE AMICK whose telephone number is (571)272-5474. The examiner can normally be reached 7:30-5 M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/THOMAS R. AMICK/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638