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 .
Priority
This application was filed on the 3rd of February 2025, and is a 371 application of PCT/JP2019/042317 filed on 29th of October 2019, which claims benefit to the foreign application JP 2019-153323 filed on 26th of August 2019.
Claim Status
On the 3rd of February 2025, Applicant’s filed pending claims 1-14.
Currently, claims 1-14 are under consideration in this Office Action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on the 3rd of Feb. 2025, and the 18th of Feb. 2026, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
However, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. Further, Applicants is reminded to file an information disclosure statement under §l.97(c). Applicant is reminded that the list of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a). Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Specification
The use of the terms LipoSEARCH (see para. 47, 80), Cholestest (see para. 82-83), TRIzol (see para. 84) and lomitapide (see para. 110), which are trade names or a marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 1-14 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Claim 1 recites “A method for screening for a substance effective for human fatty liver, comprising the steps of: culturing human hepatocytes derived from fatty liver with dimethyl sulfoxide (DMSO) to obtain a culture of human fatty liver model cells that secrete and/or accumulate lipid, administering a test substance to the culture of human fatty-liver model cells; and comparing severity of fatty-liver symptoms between cells to which the test substance is administered and cells to which the test substance is not administered.”
Claim 2 recites “A method for evaluating toxicity of a test substance to human fatty liver, comprising the steps of: culturing human hepatocytes derived from fatty liver with dimethyl sulfoxide (DMSO) to obtain a culture of human fatty-liver model cells that secrete and/or accumulate lipid, administering a test substance to the culture of human fatty-liver model cells; and comparing survival rate and severity of fatty-liver symptoms between cells to which the test substance is administered and cells to which the test substance is not administered, to evaluate effect of the test substance on human fatty liver.”
Per the 2019 Revised Patent Subject Matter Eligibility Guidance (2019 PEG) published on January 7, 2019 (84 Fed. Reg. 50), if a claim recites a limitation that can practically be performed in the human mind, the limitation falls within the mental processes grouping, and the claim recites an abstract idea. Claims recite a mental process when they contain limitations that can practically be performed in the human mind, including for example, observations, evaluations, judgments, and opinions.
The courts consider a mental process (thinking i.e. evaluating) "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).
Thus, the independent claims 1 recites “comparing” steps and 2, recites “evaluating” and “comparing” steps that are considered to embrace a mental process. See also MPEP 2106.04(a-b).
Step 1-Statutory Category: According to the 2019 Revised Patent Subject Matter Eligibility Guidelines (2019PEG), the claim is first analyzed to determine if it is directed to one of the acceptable statutory categories of invention (i.e. process, machine, manufacture, or composition of matter). Claim 2 is drawn to a method for evaluating function, status and/or activity of an immune system of a subject. Thus, the process meets the requirements for step 1 of the analysis as it is drawn to a method.
Next the claim is assessed to determine if it is directed to a judicial exception under step 2A. Under 2019 PEG, “directed to" is determined via a two-prong inquiry: (1) Does the claim recite a law of nature, a product of nature, a natural phenomenon, or an abstract idea; and (2) Does the claim recite additional element(s) that integrate the judicial exception into a practical application. The phrase, “integration of a practical application", requires the presence of an additional claim element(s) or a combination thereof to apply, rely on or use the judicial exception in a manner that imposes a meaningful limitation on the judicial exception, such that the claim does not monopolize the judicial exception. (See MPEP § 210 6.05 for examples of integration of practical application).
Step 2A Judicial Exception-Prong 1 (claim is directed to a judicial exception): Prong 2A asks whether the claim recites an abstract idea, law of nature, or natural phenomenon.
Regarding claim 1, recites “A method for screening for a substance effective for human fatty liver” (lines 1-2). Further, the claim recites “comparing severity of fatty-liver symptoms between cells to which the test substance is administered and cells to which the test substance is not administered” (lines 8-10), which requires a mental step. The claim 1, “comparing” step of the test substances is related to an abstract idea involving mental processes because a simple comparison of the test substances obtained can be performed mentally. Claims can recite a mental process even if they are described in the specification and/or claimed as being performed on a device. Hence, the claim relates to an abstract idea that is related observing a natural phenomenon involving laws of nature. Thus, the claim is directed to a judicial exception.
Regarding claim 2, recites “a method for evaluating toxicity of a test substance to human fatty liver” (lines 1-2), “comparing survival rate and severity of fatty-liver symptoms between cells to which the test substance is administered and cells to which the test substance is not administered, to evaluate effect of the test substance on human fatty liver” (lines 8-11), which requires a mental step. The claim 2, “comparing” step of comparing the survival rate is related to an abstract idea involving mental processes because a simple comparison of the data values obtained can be performed mentally. Claims can recite a mental process even if they are described in the specification and/or claimed as being performed on a device. Hence, the claim relates to an abstract idea that is related observing a natural phenomenon involving laws of nature. Thus, the claim is directed to a judicial exception.
Regarding claim 3, recites “wherein the human hepatocytes are cultured with 1 to 4 wt% DMSO”. Claim 3 just describes the human hepatocytes conditions. Therefore, claim 3 does not remedy the deficiency of claim 1. Hence, the claim relates to an abstract idea that is related observing a natural phenomenon involving laws of nature. Thus, the claim is directed to a judicial exception.
Regarding claim 4, recites “wherein the human hepatocytes are cultured with DMSO for at least 3 days”. Claim 4 just describes the human hepatocytes conditions. Therefore, claim 4 does not remedy the deficiency of claim 1. Hence, the claim relates to an abstract idea that is related observing a natural phenomenon involving laws of nature. Thus, the claim is directed to a judicial exception.
Regarding claim 5, recites “wherein the culture of human fatty-liver model cells comprises the human hepatocytes and DMSO”. Claim 5 just describes the human hepatocytes conditions. Therefore, claim 5 does not remedy the deficiency of claim 1. Hence, the claim relates to an abstract idea that is related observing a natural phenomenon involving laws of nature. Thus, the claim is directed to a judicial exception.
Regarding claim 6, recites “wherein the human hepatocytes are collected from a chimeric non-human animal having human hepatocytes”. Claim 6 just describes the human hepatocytes conditions. Therefore, claim 6 does not remedy the deficiency of claim 1. Hence, the claim relates to an abstract idea that is related observing a natural phenomenon involving laws of nature. Thus, the claim is directed to a judicial exception.
Regarding claim 7, recites “wherein culturing the human hepatocytes with DMSO improves a survival rate of the human hepatocytes.” Claim 7 just describes the human hepatocytes conditions. Therefore, claim 7 does not remedy the deficiency of claim 1. Hence, the claim relates to an abstract idea that is related observing a natural phenomenon involving laws of nature. Thus, the claim is directed to a judicial exception.
Regarding claim 8, recites “the human hepatocytes are cultured with 1 to 4 wt% DMSO for at least 3 days, wherein the culture of human fatty-liver model cells comprises the human hepatocytes and 1 to 4 wt% DMSO, and wherein culturing the human hepatocytes with 1 to 4 wt% DMSO improves a survival rate of the human hepatocytes”. Claim 8 just describes the human hepatocytes conditions. Therefore, claim 8 does not remedy the deficiency of claim 1. Hence, the claim relates to an abstract idea that is related observing a natural phenomenon involving laws of nature. Thus, the claim is directed to a judicial exception.
Regarding claim 9, dependent on claim 2, recites “wherein the human hepatocytes are cultured with 1 to 4 wt % DMSO”. Claim 9 just describes the human hepatocytes conditions. Therefore, claim 9 does not remedy the deficiency of claim 2. Hence, the claim relates to an abstract idea that is related observing a natural phenomenon involving laws of nature. Thus, the claim is directed to a judicial exception.
Regarding claim 10, dependent on claim 2, recites “wherein the human hepatocytes are cultured with DMSO for at least 3 days”. Claim 10 just describes the human hepatocytes conditions. Therefore, claim 10 does not remedy the deficiency of claim 2. Hence, the claim relates to an abstract idea that is related observing a natural phenomenon involving laws of nature. Thus, the claim is directed to a judicial exception.
Regarding claim 11, dependent on claim 2, recites “wherein the culture of human fatty-liver model cells comprises the human hepatocytes and DMSO”. Claim 11 just describes the human hepatocytes conditions. Therefore, claim 11 does not remedy the deficiency of claim 2. Hence, the claim relates to an abstract idea that is related observing a natural phenomenon involving laws of nature. Thus, the claim is directed to a judicial exception.
Regarding claim 12, dependent on claim 2, recites “wherein the human hepatocytes are collected from a chimeric non-human animal having human hepatocytes”. Claim 12 just describes the human hepatocytes conditions. Therefore, claim 12 does not remedy the deficiency of claim 2. Hence, the claim relates to an abstract idea that is related observing a natural phenomenon involving laws of nature. Thus, the claim is directed to a judicial exception.
Regarding claim 13, dependent on claim 2, recites “wherein culturing the human hepatocytes with DMSO improves a survival rate of the human hepatocytes”. Claim 13 just describes the human hepatocytes conditions. Therefore, claim 13 does not remedy the deficiency of claim 2. Hence, the claim relates to an abstract idea that is related observing a natural phenomenon involving laws of nature. Thus, the claim is directed to a judicial exception.
Regarding claim 14, dependent on claim 14, recites “the human hepatocytes are cultured with 1 to 4 wt % DMSO for at least 3 days, wherein the culture of human fatty-liver model cells comprises the human hepatocytes and 1 to 4 wt % DMSO, and wherein culturing the human hepatocytes with 1 to 4 wt % DMSO improves a survival rate of the human hepatocytes”. Claim 14 just describes the human hepatocytes conditions. Therefore, claim 14 does not remedy the deficiency of claim 2. Hence, the claim relates to an abstract idea that is related observing a natural phenomenon involving laws of nature. Thus, the claim is directed to a judicial exception.
Furthermore, there is nothing about claims 2 and 9-14 that include additional elements that are sufficient to amount to significantly more than the judicial exception since the invention as claimed does not introduce or recite any step of compositions that is beyond that which is well understood, routine and conventional.
Step 2A Judicial Exception-Prong 2 (Judicial exception is integrated into a practical application): The phrase, "integration of a practical application", requires the presence of an additional claim element(s) or a combination thereof to apply, rely on or use the judicial exception in a manner that imposes a meaningful Iimitation on the judicial exception, such that the claim does not monopolize the judicial exception. (See MPEP § 2106.05 for examples of integration of practical application). Prong 2 asks whether a claim recites additional elements that integrate the judicial exception into a practical application.
Regarding claim 1, recites “A method for screening for a substance effective for human fatty liver” (lines 1-2). Although the claim recites the additional limitations like culturing and administering, (insignificant extra-solution activity – mere data gathering/output, MPEP § 2106.05(g)). When viewed in combination or as a whole, the recited additional elements do no more than more data gathering; see MPEP § 2106.05(g) Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012). The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Further, the claim recites “comparing severity of fatty-liver symptoms between cells to which the test substance is administered and cells to which the test substance is not administered” (lines 8-10), which requires a mental step. Further, there is no additional steps requiring a practical application (e.g. applying a treatment, action, or substance). The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Therefore, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Regarding claim 2, there is no step after the step of “comparing survival rate and severity of fatty-liver symptoms between cells to which the test substance is administered and cells to which the test substance is not administered, to evaluate effect of the test substance on human fatty liver” (see lines 8-11)”, there is no additional steps requiring a practical application (e.g. applying a treatment, action, or substance). The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Therefore, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Regarding claim 3, recites “wherein the human hepatocytes are cultured with 1 to 4 wt% DMSO,” there is no additional steps requiring a practical application (e.g. applying a treatment, action, or substance). The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Therefore, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Regarding claim 4, recites “wherein the human hepatocytes are cultured with DMSO for at least 3 days”, there is no additional steps requiring a practical application (e.g. applying a treatment, action, or substance). The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Therefore, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Regarding claim 5, recites “wherein the culture of human fatty-liver model cells comprises the human hepatocytes and DMSO”, there is no additional steps requiring a practical application (e.g. applying a treatment, action, or substance). The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Therefore, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Regarding claim 6, recites “wherein the human hepatocytes are collected from a chimeric non-human animal having human hepatocytes”, there is no additional steps requiring a practical application (e.g. applying a treatment, action, or substance). The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Therefore, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Regarding claim 7, recites “wherein culturing the human hepatocytes with DMSO improves a survival rate of the human hepatocytes”, there is no additional steps requiring a practical application (e.g. applying a treatment, action, or substance). The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Therefore, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Regarding claim 8, recites “the human hepatocytes are cultured with 1 to 4 wt% DMSO for at least 3 days, wherein the culture of human fatty-liver model cells comprises the human hepatocytes and 1 to 4 wt% DMSO, and wherein culturing the human hepatocytes with 1 to 4 wt% DMSO improves a survival rate of the human hepatocytes,” there is no additional steps requiring a practical application (e.g. applying a treatment, action, or substance). The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Therefore, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Regarding claim 9, dependent on claim 2, recites “wherein the human hepatocytes are cultured with 1 to 4 wt % DMSO”. The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Therefore, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Regarding claim 10, dependent on claim 2, recites “wherein the human hepatocytes are cultured with DMSO for at least 3 days”. The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Therefore, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Regarding claim 11, dependent on claim 2, recites “wherein the culture of human fatty-liver model cells comprises the human hepatocytes and DMSO”. The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Therefore, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Regarding claim 12, dependent on claim 2, recites “wherein the human hepatocytes are collected from a chimeric non-human animal having human hepatocytes”. The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Therefore, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Regarding claim 13, dependent on claim 2, recites “wherein culturing the human hepatocytes with DMSO improves a survival rate of the human hepatocytes”. The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Therefore, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Regarding claim 14, dependent on claim 14, recites “the human hepatocytes are cultured with 1 to 4 wt % DMSO for at least 3 days, wherein the culture of human fatty-liver model cells comprises the human hepatocytes and 1 to 4 wt % DMSO, and wherein culturing the human hepatocytes with 1 to 4 wt % DMSO improves a survival rate of the human hepatocytes”. The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Therefore, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Thus, claims 2 and 9-14 meet the requirements of step 2A as being directed to a judicial exception.
Step 2B Significantly More: The "significantly more" analysis determines that a claim is patent eligible if the claims recite structures or functions that transform the natural product in a manner that make the product markedly different from the judicial exception. The claims are analyzed to determine whether the claims includes additional elements that are sufficient to amount to significantly more than the judicial exception since the invention as claimed does not introduce or recite any step of compositions that is beyond that which is well understood, routine and conventional.
Claim 1 does not add significantly more than the judicial exception. Claim 1 recites “comparing severity of fatty-liver symptoms between cells to which the test substance is administered and cells to which the test substance is not administered”. Therefore, this step does not have an additional practical step performed in this embodiment. Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed. Therefore, claim 1 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
Claim 2 does not add significantly more than the judicial exception. Claim 2 recites ““comparing survival rate and severity of fatty-liver symptoms between cells to which the test substance is administered and cells to which the test substance is not administered, to evaluate effect of the test substance on human fatty liver”. Therefore, this step does not have an additional practical step performed in this embodiment. Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed. Therefore, claim 2 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
Regarding claim 3, recites “wherein the human hepatocytes are cultured with 1 to 4 wt% DMSO”. Therefore, this step does not have an additional practical step performed in this embodiment. Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed. Therefore, claim 3 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
Regarding claim 4, recites “wherein the human hepatocytes are cultured with DMSO for at least 3 days”. Therefore, this step does not have an additional practical step performed in this embodiment. Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed. Therefore, claim 4 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
Regarding claim 5, recites “wherein the culture of human fatty-liver model cells comprises the human hepatocytes and DMSO”. Therefore, this step does not have an additional practical step performed in this embodiment. Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed. Therefore, claim 5 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
Regarding claim 6, recites “wherein the human hepatocytes are collected from a chimeric non-human animal having human hepatocytes”. Therefore, this step does not have an additional practical step performed in this embodiment. Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed. Therefore, claim 6 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
Regarding claim 7, recites “wherein culturing the human hepatocytes with DMSO improves a survival rate of the human hepatocytes”. Therefore, this step does not have an additional practical step performed in this embodiment. Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed. Therefore, claim 7 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
Regarding claim 8, recites “the human hepatocytes are cultured with 1 to 4 wt% DMSO for at least 3 days, wherein the culture of human fatty-liver model cells comprises the human hepatocytes and 1 to 4 wt% DMSO, and wherein culturing the human hepatocytes with 1 to 4 wt% DMSO improves a survival rate of the human hepatocytes.” Therefore, this step does not have an additional practical step performed in this embodiment. Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed. Therefore, claim 8 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
Regarding claim 9, dependent on claim 2 does not add significantly more than the judicial exception. The claim “wherein the human hepatocytes are cultured with 1 to 4 wt % DMSO”. Therefore, this step does not have an additional practical step performed in this embodiment. Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed. Therefore, claim 9 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
Regarding claim 10, dependent on claim 2 does not add significantly more than the judicial exception. The claim recites “wherein the human hepatocytes are cultured with DMSO for at least 3 days”. Therefore, this step does not have an additional practical step performed in this embodiment. Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed. Therefore, claim 10 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
Regarding claim 11, dependent on claim 2 does not add significantly more than the judicial exception. The claim recites “wherein the culture of human fatty-liver model cells comprises the human hepatocytes and DMSO”. Therefore, this step does not have an additional practical step performed in this embodiment. Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed. Therefore, claim 11 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
Regarding claim 12, dependent on claim 2 does not add significantly more than the judicial exception. The claim recites “wherein the human hepatocytes are collected from a chimeric non-human animal having human hepatocytes”. Therefore, this step does not have an additional practical step performed in this embodiment. Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed. Therefore, claim 12 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
Regarding claim 13, dependent on claim 2 does not add significantly more than the judicial exception. The claim recites “wherein culturing the human hepatocytes with DMSO improves a survival rate of the human hepatocytes”. Therefore, this step does not have an additional practical step performed in this embodiment. Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed. Therefore, claim 13 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
Regarding claim 14, dependent on claim 14 does not add significantly more than the judicial exception. The claim recites “the human hepatocytes are cultured with 1 to 4 wt % DMSO for at least 3 days, wherein the culture of human fatty-liver model cells comprises the human hepatocytes and 1 to 4 wt % DMSO, and wherein culturing the human hepatocytes with 1 to 4 wt % DMSO improves a survival rate of the human hepatocytes”. Therefore, this step does not have an additional practical step performed in this embodiment. Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed. Therefore, claim 14 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
It is well established that data gathering steps required to use the correlation do not add a meaningful limitation to the method as they are insignificant activity (see also MPEP 2106.05(g)).
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. (see MPEP 2106.04(a)(2)(III).)
In conclusion, claims 1-14 recite abstract ideas which are not considered to disclose eligible subject matter under 35 U.S.C. 101, and therefore are deemed not patent eligible.
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 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.
Claims 1, 2 and 9-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kazuki Shimane and Yasuhito Tanaka (US2018/0291011A1, published Oct. 11, 2018, hereinafter as “Shimane”).
Regarding claims 1, 2, 9-11, and 13-14, Shimane discloses a method for evaluating toxicity of a test substance (e.g. compound 8) to fatty liver (see e.g. Test Example 2). Further, Shimane teaches cultures of PXB cells with 2% DMSO for five days (i.e. at least three days)(see e.g. Test Example 2) corresponding to the claim limitation of culturing human hepatocytes derived from fatty liver with dimethyl sulfoxide (DMSO) to obtain a culture of human fatty-liver model cells that secrete and/or accumulate lipid. Further, Shimane discloses administering a test substance (e.g. compound 8) to the culture of human fatty-liver model cells (i.e. PXB cells) (see e.g. Test Example 2). Further, Shimane discloses screening for a substance (e.g. compound 8) effectively for human fatty liver cells compared to cells to which the test substance is not administered (i.e. control) (see e.g. Test Example 2).
Shimane does not explicitly disclose comparing severity of fatty-liver symptoms between cells to which the test substance is administered and cells to which the test substance is not administered.
Nevertheless, Shimane and applicant use the same cells i.e. PXB cells to obtain their claimed fatty liver model composition (see Specification page 28-29), thus the PXB cells of Shimane which are also cultured in 2% DMSO for at least 3 days would inherently meet the requirements comparing severity of fatty-liver symptoms between cells to which the test substance is administered and cells to which the test substance is not administered (i.e. control) (see e.g. Test Example 2).
Regarding claim 12, Shimane discloses wherein the human hepatocytes (i.e. PXB cells) are collected from a chimeric non-human animal having human hepatocytes (i.e. mouse with human hepatocyte)(see e.g. Test Example 2).
Thus, the prior art of Shimane anticipates the instant claims barring evidence to the contrary.
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.
Claims 1 and 3-8 are rejected under 35 U.S.C. 103 as being unpatentable over Mukaidani et al., (US 8278499 B2, published 2012, cited in IDS 02/03/2025) in view of Nikolaou et al., (Physiological Reports 4.21: e12944, published 2016), Breher-Esch, Stephanie, et al. (BMC Medical Genomics 11.1: 111, 2018; hereinafter as “Breher”), and Sainz Jr, Bruno, and Francis V. Chisari (Journal of virology 80.20: 10253-10257, 2006, hereinafter as “Sainz”).
Regarding claim 1 and 3-8, Mukaidani discloses a method for screening for a substance effective for human fatty liver (i.e. therapeutic agent)(see e.g. abstract; col. 11-12; claims 1-9). Mukaidani teaches a nonhuman animal showing the symptoms of human nonalcoholic steatohepatitis (i.e. fatty liver disease) wherein the fatty liver is obtained by transplanting human hepatocytes to an immunodeficient non-human animal with liver disorder (See e.g. abstract, col. 3-4, 6, 19, claim 1). Mukaidani discloses culturing human hepatocytes derived from fatty liver to obtain a culture of human fatty-liver model cells that secrete and/or accumulate lipids (see e.g. abstract, col. 16, claim 1, Examples 1-2, fig. 9). Further, Mukaidani discloses administering a test substance and comparing the test substance to cells which are not administered the test substance (i.e. therapeutic agent)(see e.g. abstract; col. 11-12; claim 5, 9).
Mukaidani does not explicitly disclose culturing hepatocytes with 1% DMSO for at least 3 days.
However, Nikolaou teaches a culture comprising the HepG2 cell line, which has been extensively used in cell-based metabolic studies, treated with 1% wt dimethyl sulfoxide (DMSO) for at least 3 days (abstract, figure 1A-D, figure 3A-3F, Figure 4, and Table 1). Further, the prior art of Sainz discloses that culturing primary hepatocytes in the presence of 1% DMSO allowed the cell culture system to maintain individual cultures for extended periods of time (up to 200 days) without splitting (see e.g. p. 10255) corresponding to the claim limitation of improves survival rate of the human hepatocytes. Additionally, the prior art of Breher discloses that genomics enables a drug target screen for the treatment of non-alcoholic fatty liver diseases and where the human hepatocytes cultures had their intracellular content increased when lipid droplets were cultured with DMSO (0.5% v/v)(see e.g. p. 7, fig. 1-2, and fig. S1).
Accordingly, it would have been prima facie obvious before the effective filing date to modify the method for screening a substance effective for human fatty liver, as taught by Mukaidani, with 1% DMSO for at least 3 days, as taught by Nikolaou, Sainz, and Breher, with a reasonable expectation of success because one of ordinary skill in the art would know that adding DMSO to the culture of human fatty liver hepatocytes with DMSO would improve the human fatty-liver model cells to secrete and/or accumulate lipid (as taught by Sainz and Breher, as discussed above). Further, Nikolaou discloses that culturing with 1% wt DMSO provides advantages to the culture of hepatocytes by attenuating lipid accumulation, inducing fatty acid oxidation and TG secretion, and augments gluconeogenesis (as taught by Nikolaou, see e.g. page 10, Fig. 1). Additionally, the prior art of Breher discloses that the genomics of lipid-laden human hepatocyte cultures enables drug target screening for the treatment of non-alcoholic fatty liver disease (see title). Thus, a person of ordinary skill in the art would have had predictable results with a reasonable expectation of success.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
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Josephine Gonzales PhD
Examiner
Art Unit 1638
/JOSEPHINE GONZALES/ Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638
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