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 .
DETAILED ACTION
Claim 7 is cancelled. Claims 8-10 are newly added. Claims 1-6 and 8-10 are pending and under examination.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/24/2025 has been entered.
Claim Objections
Claims 1 and 8 are objected to because of the following informalities: the claims contain grammatical errors. Claim 1 contains an acronym (iPS) but does not define what said acronym stands for. Claim 1 may be amended to recite:
A method for evaluating hepatotoxicity, comprising:
adding a drug to a co-culture system comprising a liver organoid and blood cells; and
evaluating the hepatotoxicity of the drug to the organoid,
wherein the liver organoid is fabricated with drug-induced liver injury (DILI).
Claim 8 may be amended to recite: wherein the blood cells are derived from a patient with drug-induced liver injury (DILI).
Appropriate correction is required.
Response to Arguments
Applicant’s arguments with respect to the rejection of claims 1-6 under 35 U.S.C. 103 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Claim Rejections - 35 USC § 112(b)
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 1-6 and 8-10 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: wherein the liver organoid is fabricated using iPS cells derived from a patient of drug-induced liver injury (DILI). It is unclear whether fabricating the organoid from iPS cells derived from a patient with DILI is an additional step required by the method of claim 1, or if the wherein clause is to be treated as a product-by-process limitation within a process claim.
Claims 2-6 and 8-10 are also rejected as they depend from claim 1.
Claims 3 and 9 recite: a method for identifying a biomarker, comprising performing the method for evaluating hepatoxicity according to claim 1 for multiple specimens of the liver organoid. According to the instant specification different specimens are interpreted as samples taken from different organoids derived from different sources, i.e., para. [0063] recites: “Accordingly, the concentrations of various cytokines in the culture supernatant are compared between specimens with cytotoxicity (such as an organoid derived from a patient) and specimens without cytotoxicity (such as an organoid derived from a healthy individual)”. Because of the claim recites multiple specimens of the liver organoid, it is unclear if the claim means that specimens are taken from the same organoid, or if the claim means that specimens are taken from different organoids derived from different sources.
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.
Claims 1-4 and 8-10 are rejected under 35 U.S.C. 101 because the claimed inventions are directed to abstract ideas without significantly more.
See MPEP 2106.04(a)(2)III, which states: The courts consider a mental process (thinking) that “can be performed in the human mind, or by a human using a pen and paper” to be an abstract idea. CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 1372, 99 USPQ2d 1690, 1695 (Fed. Cir. 2011). As the Federal Circuit explained, “methods which can be performed mentally, or which are the equivalent of human mental work, are unpatentable abstract ideas the ‘basic tools of scientific and technological work’ that are open to all.’” 654 F.3d at 1371, 99 USPQ2d at 1694 (citing Gottschalk v. Benson, 409 U.S. 63, 175 USPQ 673 (1972)). See also Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012) (“‘[M]ental processes[] and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work’” (quoting Benson, 409 U.S. at 67, 175 USPQ at 675)); Parker v. Flook, 437 U.S. 584, 589, 198 USPQ 193, 197 (1978) (same). Accordingly, the “mental processes” abstract idea grouping is defined as concepts performed in the human mind, and examples of mental processes include observations, evaluations, judgments, and opinions.
Claims 1, 2, and 8 are directed to a method for evaluating hepatotoxicity, comprising adding a drug to a co-culture system comprising a liver organoid and blood cells; and evaluating the hepatotoxicity of the drug to the organoid, wherein the liver organoid is fabricated by using iPS cells derived from a patient with drug-induced liver injury (DILI). The only active step required by the claims is: adding a drug to a co-culture system comprising a liver organoid and blood cells.
Claims 3 and 9 are directed to a method for identifying a biomarker, however, the only active step required by the claims is: adding a drug to a co-culture system comprising a liver organoid and blood cells.
Claims 4 and 10 are directed to a method for screening a drug, however, the only active step required by the claim is: adding a drug to a co-culture system comprising a liver organoid and blood cells.
This judicial exception is not integrated into a practical application because the claims are directed to . The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims are directed to a mental process, i.e., an observation that can performed in the human mind.
Prong 1 - Statutory category: Under 35 USC 101, the claimed invention must be “any new and useful process, machine, manufacture, or composition of matter.” The invention falls under one of the statutory categories (a process) identified in 35 USC 101.
Prong 2A – Judicial exception: Here, the claimed invention is a process but is directed to the judicial exception, specifically an abstract idea. The three judicial exception categories are: enumerated abstract idea, law of nature, and natural phenomenon (product of nature).
Here, the inventions are mental process comprising evaluating hepatotoxicity, identifying biomarkers, and screening drugs, and are therefore directed to abstract ideas and fall within the judicial exception category.
Prong 2B: Judicial Exception/Significantly More: The “significantly more” analysis is a determination whether a claim is eligible if the claim(s) recites additional elements that integrate the judicial exception into a practical application. Integration requires an additional element in the claim to apply, rely on, or use the judicial exception in a manner than imposes a meaningful limit on the judicial exception.
Claims 1-4 and 8-10 are drawn to abstract ideas with no additional elements other than adding a drug to a co-culture system comprising a liver organoid and blood cells. Vulto (WO 2017/216113 A2) teaches a cell culture device comprising a microfluidic network comprising an organoid compartment (p. 4, lines 1-6). Vulto teaches that the device of the present invention is configured for spatially controlled co-culture with other cells (p. 31, lines 8-9). Vulto teaches that the cell culture device comprises biological tissue (p. 22, line 33) which may comprise an organoid comprising cells obtained from the liver (p. 23, line 17). Vulto teaches that the cell culture device may be considered an assay plate (p. 23, line 1) and teaches that one or more of a patient’s own T cells, B cells, lymphocytes, dendritic cells or monocytes (i.e., immunocompetent blood cells) may be introduced into the assay plate (p. 36, lines 30-33), which, as stated, may comprise an organoid (p. 23, para. 1). Vulto teaches that the assay plate may be used in an assay in which a test solution that may comprise a pharmaceutical drug is introduced into the microfluidic network and the effects of the test solution on the organoids are observed (p. 36, lines 15-19). Vulto teaches that organoids have been developed from induced pluripotent stem cells, (paragraph spanning pages 1and 2) i.e., iPS cells.
Therefore, the only active step required by the claim is well-understood, routine, and conventional and the claims do not recite any limitations significantly more than the judicial exception.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or 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.
Any references that teach adding a drug to a co-culture system comprising a liver organoid and blood cells, wherein the liver organoid is fabricated by using iPS cells derived from a patient with drug-induced liver injury, meet the limitations of claims 1-4 and 8-10.
Claims 1-6 and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Vulto et al., (WO 2017/216113 A2), previously cited, in view of Umezawa et al., (US Patent No. 12,110,507 B2), with an effective filing date of 12/27/2017.
Regarding claims 1-4, Vulto teaches a cell culture device comprising a microfluidic network comprising an organoid compartment (p. 4, lines 1-6). Vultuo teaches that the device of the present invention is configured for spatially controlled co-culture with other cells (p. 31, lines 8-9). Vulto teaches that the cell culture device comprises biological tissue (p. 22, line 33) which may comprise an organoid comprising cells obtained from the liver (p. 23, line 17). Vulto teaches that the cell culture device may be considered an assay plate (p. 23, line 1) and teaches that one or more of a patient’s own T cells, B cells, lymphocytes, dendritic cells or monocytes (i.e., immunocompetent blood cells) may be introduced into the assay plate (p. 36, lines 30-33) in combination with the patient’s biological tissue (p. 36, para. 5), which may be an organoid as disclosed in an earlier portion of the Vulto reference. Vulto teaches that the assay plate may be used in an assay in which a test solution that may comprise a pharmaceutical drug is introduced into the microfluidic network and the effects of the test solution on the organoids are observed (p. 36, lines 15-19). Vulto teaches that organoids have been developed from induced pluripotent stem cells, (paragraph spanning pages 1and 2) i.e., iPS cells. In summary, Vulto teaches a cell culture device that is configured for co-culture of blood cells with cells that may comprise an organoid comprising cells obtained from the liver, and may be used to study the effects of pharmaceutical drugs.
Vulto does not teach iPS cells derived from a patient with drug-induced liver injury.
However, Umezawa teaches a method of preparing functional hepatic progenitor cells (Abstract) using iPS cells derived from a drug-induced liver injury patient (Column 3, line 15).
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have fabricated the organoid using iPS cells, as taught by Vulto, derived from a patient with drug-induced liver injury, as taught by Umezawa. One of ordinary skill in the art would have been motivated to do so because Umezawa teaches that functional hepatic progenitor cells obtained by the method according to the invention are useful for regenerative medicine or drug toxicity evaluation (Column 4, Advantageous Effects of Invention). One of ordinary skill in the art would have had a reasonable expectation of success because Vulto and Umezawa are in the same field of endeavor of cell culture and drug toxicity assays.
Regarding claim 5, as discussed above, the combination of Vulto and Umezawa teaches the method of instant claim 1. Vulto teaches a kit comprising the cell culture device or assay plate of the invention. It would have been obvious to one of ordinary skill in the art to fabricate the organoid of the kit of Vulto using iPS cells derived from a patient with drug-induced liver injury, as taught by Umezawa.
Regarding claims 8-10, as discussed above, Vulto teaches a cell culture device/assay plate comprising an organoid and that may comprise cells obtained from the liver (p. 23, line 17). Vulto teaches that the assay plate may be used in an assay in which a test solution that may comprise a pharmaceutical drug is introduced into the microfluidic network and the effects of the test solution on the cells, cell aggregates, organoids, or embryonic body are observed (p. 36, lines 15-19). Therefore, it would have been obvious to one of ordinary skill in the art to add one or more drugs to one or more co-culture systems comprising a liver organoid and blood cells to determine the effects of said drug on the organoids, based on the teachings of Vulto.
Vulto teaches that organoids have been developed from induced pluripotent stem cells, (paragraph spanning pages 1and 2) i.e., iPS cells, while Umezawa teaches a method of preparing functional hepatic progenitor cells (Abstract) using cells iPS derived from a patient with drug-induced liver injury (Column 3, line 15). Vulto teaches that the biological tissue, i.e., the organoid, may be derived from healthy or diseased tissue and may be obtained from a patient (p. 23, line 19) and teaches that one or more of a patient’s own T cells, B cells, lymphocytes, dendritic cells or monocytes (i.e., immunocompetent blood cells) may be introduced into the assay plate (p. 36, lines 30-33).
Therefore, if one of ordinary skill in the art were to generate an organoid as taught by Vulto using iPS cells derived from a patient with drug-induced liver injury, as taught by Umezawa, it would have been obvious to one of ordinary skill in the art that the drug-induced liver injury patient’s own immunocompetent blood cells may be added to the assay plate comprising the organoid, based on the teachings of Vulto. One of ordinary skill in the art would have been motivated to do so because Vulto teaches that the organoid may be derived from healthy or diseased tissue and may be obtained from a patient (p. 23, line 19).
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Vulto et al., (WO 2017/216113 A2) and Umezawa et al., (US Patent No. 12,110,507 B2) as applied to claim 5 above, and further in view of Nahmias et al (WO 2020/170239 A1), with an effective filing date of 02/21/2019.
Regarding claim 6, as discussed above, the combination of Vulto and Umezawa teach the kit of instant claim 5.
Vulto teaches that the assay plate may be used in a toxicity assay (p. 37, line 5) but does not teach that the kit comprises a dead cell detection reagent.
However, Nahmias a method for generating organoids for high throughput analysis for drug screening (Abstract) and teaches a LIVE/DEAD cytotoxicity kit (p. 73, line 19).
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have included a LIVE/DEAD cytotoxicity kit, as taught by Nahmais, in the kit comprising blood cells and a liver organoid fabricated using iPS cells, as taught by Vulto, derived from a patient with drug-induced liver injury, as taught by Umezawa. One of ordinary skill in the art would have been motivated to do so because Nahmias teaches that the LIVE/DEAD cytotoxicity kit is used for determining liver cell viability in the presence of different compounds (p. 73, lines 17-19). One of ordinary skill in the art would have had a reasonable expectation of success because Vulto, Umezawa, and Nahmias are in the same field of endeavor of drug toxicity assays.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL EMILY MARTIN whose telephone number is (703)756-1416. The examiner can normally be reached M-Th 8:30-16:00, F 8:30-10:00 EST.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/RACHEL EMILY MARTIN/Examiner, Art Unit 1657