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 Status
Claims 6-10 are pending and are considered on the merits.
Priority
This application is a 371 of PCT/JP2022/007494 (filed on 02/24/2022), which claims benefit from foreign application JAPAN 2021-030911 (filed on 02/26/2021). The priority claim of the instant application has been granted and the earliest benefit date is 02/26/2021 from the foreign application JAPAN 2021-030911.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 08/23/2023 and 04/21/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. The corresponding signed and initialed PTO forms 1449 have been mailed with this action.
Claim Objections
Claim 6 is objected to because of the following informalities:
Claim 6 recites “a Human fatty-liver” in line 3. It seems the word “Human” is typographically capitalized. It is recommended to change to “a human fatty-liver”.
Additionally, claim 6 recites an abbreviation “VLDL” in line 4. An abbreviation should be preceded in its first occurrence by the specific identity of the entity which the abbreviation is intended to represent. It is recommended to recite “very low density lipoprotein (VLDL)”.
Appropriate correction is required.
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 6-10 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 6 recites the term “Large-VLDL”, claim 8 recites the terms “Large-VLDL, Medium-VLDL and Small-VLDL”. A claim may be rendered indefinite by reference to term of an object that is variable (see MPEP 2173.05(b), II). Specifically, the terms “Large-VLDL, Medium-VLDL and Small-VLDL” are relative terms which renders the claims indefinite. The specification merely recites exemplary particle sizes of VLDL “L”, “M" and “S” in Table 1 in page 27. However, the terms “Large-VLDL, Medium-VLDL and Small-VLDL” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Claims 7 and 9-10 are rejected as being dependent from claim 6 but not resolving the ambiguity.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 9 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 9 recites the cell culture further contains dimethyl sulfoxide. However, since the base claim 6 has already recited the cell culture being in a medium containing dimethyl sulfoxide in line 7, the limitation recited in dependent claim 9 fails to further limit the subject matter of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 6-10 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, the claims listed above do not recite something significantly different than a judicial exception. Judicial exceptions include abstract ideas, laws of nature/natural principles, natural phenomena, and natural products. As described in MPEP § 2106, in addition to the terms laws of nature, physical phenomena, and abstract ideas, judicial exceptions have been described using various other terms, including natural phenomena, products of nature, natural products, naturally occurring things, scientific principles, systems that depend on human intelligence alone, disembodied concepts, mental processes and disembodied mathematical algorithms and formulas, for example. The exceptions reflect the judicial view that these fundamental tools of scientific and technological work are not patentable.
The claimed invention is not patent eligible since each claim, as a whole, does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims relate to screening for a substance by comparing Large-VLDL between cell cultures with and without the substance, that involve steps that may be performed mentally and that do not add significantly more to the claimed invention. Specifically, these steps that may be performed mentally relate to comparing the amount of Large-VLDL in culture supernatant between cell cultures with and without the test substance.
This conclusion was reached by following the procedure set forth in an official guidance memorandum issued on March 4, 2014 by Andrew Hirshfeld, Deputy Commissioner for Patent Examination Policy, entitled “Guidance For Determining Subject Matter Eligibility Of Claims Reciting Or Involving Laws of Nature, Natural Phenomena, & Natural Products” (hereinafter “guidance”; available at http://www.uspto.gov/patents/law/exam/myriad-mayo_guidance.pdf).
To expound upon the above, the decision in Alice Corp. v. CLS Bank made clear that it applies the framework set forth in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. (2012) (Mayo) to analyze all claims directed to laws of nature, natural phenomena and abstract ideas for subject matter eligibility under 35 USC 101 (also see reasoning set forth below regarding natural principals). The instructions in Alice indicate the following:
1) The same analysis should be used for all types of judicial exceptions, whereas prior USPTO guidance applied a different analysis to abstract ideas (Bilski guidance in MPEP at 2106 (II)(B)) than to claims with laws of nature (Mayo guidance in MPEP 2106.01).
2) The same analysis should be used for all categories of claims (e.g., product and process claims) where prior guidance applied a different analysis to process claims (Bilski guidance).
The basic inquiries remain the same, however, as explained in MPEP 2106(I). With regard to that, and analyzing the instant claims herein, the first question to ask is do the claims fall into one of the four categories of invention (i.e., step 1)? The answer here is “yes”. The claims are drawn to a process.
The next question relates to whether the claimed invention is directed to a law of nature, a natural phenomenon, or an abstract idea (i.e. step 2A prong one). The invention as presently claimed is directed to a judicial exception, since the claimed invention requires the act of comparing the amount of Large-VLDL in culture supernatant between cell cultures with and without the test substance. Each of these steps can be performed mentally, and are thus considered abstract ideas. The answer to step 2A prong one is thus “yes”.
Proceeding to step 2A prone two of the analysis becomes important to determine whether the claims recite additional elements that integrate the judicial exception into a practical application. The claims do not recite any additional elements based on the steps directed to judicial exceptions, thus do not provide improvement to a current method in any aspect, or do not integrate the judicial exceptions into any specific or practical application. The answer to step 2A prong two is thus “no”.
Turning to step 2B, the claims as a whole do not amount to significantly more than the abstract ideas since they do not comprise an improvement to an technology or field, or a computer, or effect a transformation of a particular article to a different state or thing or add significantly specific limitations to the abstract ideas other than what is well understood, routine and conventional in the field. It is well established that the mere physical or tangible nature of additional elements such as evaluating Large-VLDL amount does not automatically confer eligibility on a claim directed to an abstract idea (see, e.g., Alice Corp. v. CLS Bank Int’l, 134 S.Ct. 2347, 2358-59 (2014)). The claimed invention is thus drawn to abstract ideas (that cannot confer patent eligibility as discussed above), and a step of administering a test substance to a human fatty-liver model cell culture.
Here however, the step of administering a test substance to a human fatty-liver model cell culture, cannot be relied upon to confer eligibility. This is because, as stated supra, this element does not add significantly specific limitations to the abstract ideas other than what is well understood, routine and conventional in the field, and the claims do not recite any additional elements/steps based on the steps directed to judicial exceptions. Accordingly, the claims encompass methods that do not apply the abstract idea in a meaningful or specific way so as to render the claims practically applied. The answer to step 2B above is thus “no”.
In light of the above considerations and cited guidance, the claims are thus drawn to patent ineligible subject matter and are rejected therefore.
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 6-7 and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Hata et al. (Biomedical Research (Tokyo). 2020 Feb. 1st, 41(1): 33-42, cited in IDS 08/23/2023) in view of Khetani et al., (US 2018/0172668, cited in IDS 04/21/2025) and Fon Tacer et al., (J Lipids. 2011:783976, p. 1-14).
With respect to claim 6, Hata teaches a method for screening anti-lipidemic drugs using an in vitro system (see e.g., title and abstract), thus teaches the preamble a method for screening for a substance having an effect on dyslipidemia.
Hata teaches human hepatocytes are transplanted and repopulated in immunodeficient mice, and fresh hepatocytes are isolated from the humanized mouse livers (“PXB-cells”, p. 34, para. 1 and Fig 1), thus teaches a human liver model cell culture. Hata teaches evaluation of anti-lipidemic agents by administering a test substance such as fenofibrate to the human liver model cell culture (p. 39, right col., para “Evaluation of anti-lipidemic agents by lipoprotein profiles of PXB-cells”, see Table 4 and Fig. 6). Hata teaches the PXB-cells produce both VLDL and LDL, and mainly release cholesterol and triglycerides in the VLDL fraction (p. 38, right col., see Table 3 and Fig. 3), thus teaches the culture supernatant of the cells contains VLDL and LDL in which the VLDL is contained more than the LDL. Hata teaches the PXB-cells are obtained by culturing human hepatocytes derived from the humanized mouse livers in a medium containing dimethyl sulfoxide (DMSO, see p. 34, right col, para 1).
However, Hata is silent on the cell culture being a human fatty-liver model cell culture, nor teach the human hepatocytes are derived from fatty liver.
Khetani teaches a method for high throughput screening and evaluation of drug candidates using an in vitro human hepatocytes cell culture system (see e.g., abstract). Khetani teaches the hepatocytes may be obtained from human donors suffering from a liver disorder, such as non-alcoholic fatty liver disease (NAFLD) ([0008], [0012], also see reference claims 9-10 and 15-16). Thus, Khetani teaches a human fatty-liver model cell culture that is obtained by culturing human hepatocytes derived from fatty liver.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method for screening for anti-lipidemic drugs using a human liver model cell culture disclosed by Hata, by substituting the human liver with human fatty liver (i.e., using a human fatty-liver model cell culture derived from fatty liver) as suggested by Khetani with a reasonable expectation of success. Since Hata aims to screen for anti-lipidemic drugs using a chimeric human liver model cell culture (see e.g., title and abstract), and since Khetani reduces to practice a method for high throughput screening and evaluation of drug candidates using human hepatocytes obtained from human donors suffering from a liver disorder, such as non-alcoholic fatty liver disease (e.g., abstract, [0008], [0012], also see reference claims 9-10 and 15-16), one of ordinary skill in the art would have had a reason to derive human hepatocytes from fatty liver as suggested by Khetani in the method of Hata in order to screen for drug candidates to treat a liver disorder such as non-alcoholic fatty liver disease (see Khetani claims 15-16).
Furthermore, since prior art Fon Tacer teaches in nonalcoholic fatty liver disease, deregulation of fat metabolism in the fatty liver is accompanied by overproduction of very-low-density lipoproteins (VLDL) (p. 2, left col, para 2), and since Hata teaches the human hepatocytes (PXB-cells) produce both VLDL and LDL, and mainly release cholesterol and triglycerides in the VLDL fraction (p. 38, right col., see Table 3 and Fig. 3), one of ordinary skill in the art would have had a reasonable expectation of success in obtaining culture supernatant of the human hepatocytes derived from fatty liver that contains VLDL and LDL in which the VLDL is contained more than the LDL.
In regard to evaluating the anti-lipidemic effect of the test substance, Hata compares the lipoprotein profiles in the culture supernatant of PXB-cells treated with the test substance to that of untreated control cells (p. 39, right col, para “Evaluation of anti-lipidemic agents by lipoprotein profiles of PXB-cells”, also see Table 4 and Fig. 6).
However, Hata is silent on comparing an amount of Large-VLDL among VLDL in culture supernatant of the human fatty-liver model cell culture.
Fon Tacer teaches fatty liver-associated dyslipidemic profile is characterized by increased large VLDL and small dense LDL, and decreased large HDL correlated with the intrahepatic lipid content (p. 2, left col., para 2).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method for comparing lipoprotein profiles in the human fatty-liver model cell culture suggested by Hata in view of Khetani and Fon Tacer, by choosing the amount of large VLDL as one lipoprotein profile as suggested by Fon Tacer with a reasonable expectation of success. Since Hata teaches comparing the lipoprotein profiles to evaluate the anti-lipidemic effect of the test substance (p. 39, right col, para “Evaluation of anti-lipidemic agents by lipoprotein profiles of PXB-cells”, also see Table 4 and Fig. 6), and since Fon Tacer teaches increased amount of large VLDL is a characteristic in fatty liver-associated dyslipidemic profile that correlates with the intrahepatic lipid content (p. 2, left col., para 2), one of ordinary skill in the art would have had a reason to choose the amount of large VLDL as a comparison marker in order to evaluate the anti-lipidemic effect of the test substance in the human fatty-liver model cell culture.
With respect to claim 7 directed to the cell culture being a monolayer cell culture, Hata teaches the PXB-cells are seeded and maintained in a 24-well microplate (p. 34, right col, para 1) and Figure 2 (a) shows the PXB-cells are cultured as a monolayer.
With respect to claim 9 directed to the cell culture further containing dimethyl sulfoxide, as stated supra, Hata teaches the PXB-cells are cultured in a medium containing dimethyl sulfoxide (DMSO, see p. 34, right col, para 1).
With respect to claim 10 directed to the human hepatocytes being collected from a chimeric non-human animal having human hepatocytes, as stated supra, Hata teaches human hepatocytes are transplanted and repopulated in immunodeficient mice (i.e., a chimeric non-human animal), and fresh human hepatocytes are isolated from the humanized mouse livers (“PXB-cells”, p. 34, para. 1 and Fig 1).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Hata et al. (Biomedical Research (Tokyo). 2020 Feb. 1st, 41(1): 33-42, cited in IDS 08/23/2023) in view of Khetani et al., (US 2018/0172668, cited in IDS 04/21/2025) and Fon Tacer et al., (J Lipids. 2011:783976, p. 1-14), as applied to claim 6 above, and further evidenced by Wojczynski et al., (Lipids in Health and Disease. 2011; 10:181, p. 1-11) and in view of Packard et al., (Front. Endocrinol. 2020;11:252, p. 1-15).
Claim 8 is directed to the VLDL including Large-VLDL, Medium-VLDL and Small-VLDL, and the Large-VLDL being contained in a ratio of 70 mass% or more of total VLDLs. It must be noted that these wherein clauses do not recite an active step in the claimed method, but only the results of the step of the human fatty-liver model cell culture being obtained by culturing human hepatocytes derived from fatty liver as suggested by Hata in view of Khetani and Fon Tacer. MPEP 2111.04 I states a whereby clause (or a wherein clause) “in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore, these wherein clauses do not provide any patentable weight in determining patentability of the claimed method.
Nevertheless, prior art Wojczynski evidences that VLDL includes subclasses of Large-VLDL, Medium-VLDL and Small-VLDL based on lipoprotein particle sizes (p. 9, right col, para 1 and Figure 6). Furthermore, Packard teaches increased levels of plasma triglyceride are associated with the accumulation of large, triglyceride-rich VLDL (VLDL1 particles with a diameter range of 50-80 nm) containing about 70% triglyceride by mass, while smaller VLDL (VLDL2 which are 30-50 nm in diameter and consist of about 30% triglyceride) show a moderate elevation (Figure 1A) (p. 2, right col, para “Accumulation of Large VLDL and Remnants in Hypertriglyceridemia”). Figure 1A shows VLDL1 (i.e., Large-VLDL) is contained in a ratio of 70 mass% or more of total VLDLs in hypertriglyceridemia (VLDL1/(VLDL1+VLDL2) = ~200/(200+40) = 83%).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have appreciated that the VLDL in the culture supernatant of Hata in view of Khetani and Fon Tacer includes subclasses of Large-VLDL, Medium-VLDL and Small-VLDL based on lipoprotein particle sizes evidenced by Wojczynski (p. 9, right col, para 1 and Figure 6), and the Large-VLDL is likely contained in a ratio of 70 mass% or more of total VLDLs as suggested by Packard since Hata in view of Khetani and Fon Tacer suggest a human fatty-liver model cell culture that is characterized by increased large VLDL (Fon Tacer, p. 2, left col., para 2) and Packard teaches large VLDL is accumulated in hypertriglyceridemia and is contained in a ratio of 70 mass% or more of total VLDLs (p. 2, right col, para “Accumulation of Large VLDL and Remnants in Hypertriglyceridemia” and Figure 1A).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Provisional Double Patenting Rejections
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 6-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending claims 1-14 of copending Application No: 19/044,583 in view of Fon Tacer et al., (J Lipids. 2011:783976, p. 1-14) and evidenced by Hata et al. (Biomedical Research (Tokyo). 2020 Feb. 1st, 41(1): 33-42, cited in IDS 08/23/2023). Although the claims at issue are not identical, they are not patentably distinct from each other.
Copending application claims recite a method for screening for a substance effective for human fatty liver, comprising the steps of culturing human hepatocytes derived from fatty liver with 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 (reference claim 1, related to instant claims 6 and 9), wherein the human hepatocytes are collected from a chimeric non-human animal having human hepatocytes (reference claim 6, related to instant claim 10).
However, the copending claims are silent on the culture supernatant containing VLDL and LDL in which the VLDL is more than the LDL, nor recite comparing large-VLDL in culture supernatant in instant claim 6.
Fon Tacer teaches deregulation of fat metabolism in the fatty liver is accompanied by overproduction of very-low-density lipoproteins (VLDL), as well as small, dense LDL, and elevated VLDL is likely the key metabolic disturbance and correlates strongly with obesity and metabolic syndrome (p. 2, left col, para 2 and see Fig 1), thus suggests the culture supernatant of fatty-liver model cells contains VLDL and LDL in which the VLDL is more than the LDL. Fon Tacer teaches fatty liver-associated dyslipidemic profile is characterized by increased large VLDL and small dense LDL, and decreased large HDL correlated with the intrahepatic lipid content (p. 2, left col., para 2).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method comprising comparing fatty-liver symptoms in the human fatty-liver model cell culture recited in copending claims, by choosing comparing the amount of large VLDL as one fatty-liver marker as suggested by Fon Tacer with a reasonable expectation of success. Since Fon Tacer teaches increased amount of large VLDL is a characteristic in fatty liver-associated dyslipidemic profile that correlates with the intrahepatic lipid content (p. 2, left col., para 2), one of ordinary skill in the art would have had a reason to choose the amount of large VLDL as a comparison marker in order to evaluate the anti-lipidemic effect of the test substance in the human fatty-liver model cell culture.
Furthermore, since Fon Tacer teaches in nonalcoholic fatty liver disease, deregulation of fat metabolism in the fatty liver is accompanied by overproduction of very-low-density lipoproteins (VLDL) as well as small, dense LDL, and elevated VLDL is likely the key metabolic disturbance and correlates strongly with obesity and metabolic syndrome (p. 2, left col, para 2), one of ordinary skill in the art would have had a reasonable expectation of success in obtaining culture supernatant of the human hepatocytes derived from fatty liver that contains VLDL and LDL in which the VLDL is contained more than the LDL.
However, copending claims are silent on the cell culture being a monolayer cell culture in instant claim 7.
Regarding culturing human hepatocytes, prior art Hata evidences that the human hepatocytes (PXB-cells) are seeded and maintained in a 24-well microplate (p. 34, right col, para 1) and Figure 2 (a) shows the PXB-cells are cultured as a monolayer.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have appreciated that the human hepatocytes cell culture recited in copending claims would have been a monolayer cell culture as evidenced by Hata.
In regard to the wherein clause in instant claim 8, it must be noted that these wherein clauses do not recite an active step in the claimed method, but only the results of the step of the human fatty-liver model cell culture being obtained by culturing human hepatocytes derived from fatty liver recited in copending claims. Therefore, these wherein clauses do not provide any patentable weight in determining patentability of the instantly claimed method. See MPEP 2111.04 (I).
Since the instant application claims are obvious over cited application claims, in view of Fon Tacer and evidenced by Hata, said claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims in the copending application have not in fact been patented.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jianjian Zhu whose telephone number is (571)272-0956. The examiner can normally be reached M - F 8:30AM - 4PM (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Douglas (Doug) Schultz can be reached on (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JIANJIAN ZHU/Examiner, Art Unit 1631