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 .
Election/Restrictions
Applicant’s election of Group I, claims 1-14, and the species P450-ferredoxin reductase-ferredoxin fusion protein in the reply filed on 10/22/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Priority
The instant application filed on 06/27/2023 is a 371 of PCT/US2021/065430 filed on 12/29/2021 and claims priority to U.S. Provisional Application Number 63/131,952 filed on 12/30/2020. PRO 63/131,952 finds support for the instantly claimed invention; therefore, the effective filing date of the instant application is 12/30/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/26/2024, 02/03/2025, and 11/18/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112(b), Indefiniteness
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.
Claims 1-7 are rejected under 35 U.S.C. 112(b) 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 “expressing one or more cholesterol catabolizing protein in at least one liver cell of the subject; reducing a growth rate of the at least one liver cell”; however, it is unclear if both the expressing and reducing steps are required, or if one is required in this method since “and” /“or” is not used to connect the two phrases. For the purposes of applying prior art, the Examiner has interpreted the claim to require both the expression and reduction methods.
Claims 2-7 are included in this rejection because they depend on rejected independent claim 1 and fail to rectify the noted deficiency.
Claim Rejections - 35 USC § 112(a), Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-2 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. Claims 1-2 are not enabled because the claims do not recite administering any compound or providing anything other than claiming a naturally occurring process; therefore, Applicant is not preventing or treating hepatocellular carcinoma.. Additionally, the instant specification does not reasonably provide enablement for preventing hepatocellular carcinoma. Therefore, claims 1-2 are not enabled for treating or preventing hepatocellular carcinoma.
Claims 3-14 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for treatment of hepatocellular carcinoma, does not reasonably provide enablement for preventing hepatocellular carcinoma. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. Therefore, claims 3-14 are not enabled for prevention of hepatocellular carcinoma.
In re Wands (858 F2d, 721, 727, 8 USPQ 2d 1400, 1404 (Fed Cir. 1988)), the issue of enablement in molecular biology was considered. It was held that the following factors should be considered to determine whether the claimed invention would require the skilled artisan undue experimentation:
Amount of experimentation necessary;
Amount of direction or guidance presented;
Presence or absence of working examples;
Nature of the invention;
State of the prior art;
Relative skill of those in the art;
Predictability or unpredictability of the art; and
Breadth of the claims.
Independent claim 1 recites:
A method of treating or preventing hepatocellular carcinoma in a subject in need thereof comprising: expressing one or more cholesterol catabolizing protein in at least one liver cell of the subject; reducing a growth rate of the at least one liver cell.
Nature of the invention: The invention is directed towards a method of treating or preventing hepatocellular carcinoma in a subject in need thereof through expression of a cholesterol catabolizing protein in a liver cell, and wherein the cholesterol catabolizing protein reduces the growth rate of the liver cell.
Breadth of the claims: As claimed, the method of treating or preventing hepatocellular carcinoma in a subject in need thereof comprises expressing one or more cholesterol metabolizing proteins within one or more liver cells.
Amount of direction or guidance presented: The instant Specification states “The terms "prevent" and "prevention" as used herein mean avoidance of the occurrence or of the re-occurrence of a disease as specified herein, by the administration of an antibody construct according to the invention to a subject in need thereof” (see, e.g., instant Spec, [0047]). Additionally, the instant Specification states “Also disclosed are methods of treating or preventing hepatocellular carcinoma in a subject in need thereof comprising: administering a composition to the subject, wherein the composition comprises one or more compounds that support expression of at least one cholesterol catabolizing protein in a mitochondrion of a mammalian cell” (see, e.g., instant Spec, [0008]), and “In many embodiments the method may be useful in preventing or reducing likelihood of a liver cell being resistant to chemotherapy and/or may result in the liver cell may enter the apoptotic pathway after expressing the one or more cholesterol catabolizing protein” (see, e.g., instant Spec, [0008]). Since the liver cell discussed in the instant Specification already has carcinoma (see, e.g., instant Spec, [0008], the Applicant is not preventing, but merely treating. Moreover, the instant Specification states “Similarly, a prophylactically administered treatment need not be completely effective in preventing the onset of a condition to constitute a viable prophylactic method or agent” (see, e.g., instant Spec, [0048]).
The instant Specification does not provide guidance, methods, or results showing that the expression of a cholesterol catabolizing protein prevents hepatocellular carcinoma. The methods provided within the instant Specification (see, e.g., instant Specification, Example 1) are for treatment. The instant Specification does not provide guidance on whether administration of a cholesterol catabolizing protein would prevent hepatocellular carcinoma in vivo, such as a subject in need thereof because the instant Specification only provides one example of killing liver cells in cell culture. The instant Specification does not provide guidance on whether administration of a cholesterol catabolizing protein to a liver cell would prevent cellular resistance to chemotherapy, both within cell culture and within subjects in need thereof. Therefore, it is unclear if these methods used for cell culture would be applicable to treating a subject in need thereof, such as a human patient with hepatocellular carcinoma.
Presence or absence of working examples: The instant Specification provides an example of expressing a cholesterol catabolizing protein within liver cells in a cell culture method (see, e.g., instant Spec, Example 1); however, this example does not extrapolate to expression of a cholesterol catabolizing protein within a human patient with hepatocellular carcinoma. Moreover, there is no guidance on how this example can be extrapolated to prevent hepatocellular carcinoma, especially within a patient in need thereof, because Example 1 merely shows liver cell death due to treatment with the cholesterol catabolizing protein in a cell culture method. Therefore, the only working example in the instant Specification is for expressing a cholesterol catabolizing protein within a liver cell in a cell culture method and measuring cell viability and cell growth; however, there is no extrapolation to how this would be used to prevent hepatocellular carcinoma in a subject in need thereof. Moreover, there are no examples showing how treatment with a cholesterol catabolizing agent would prevent mammalian cells from being resistant to chemotherapy, both in cell culture and in patients in need thereof.
Based on Applicant’s disclosure, the Application would not be enabled for the prevention of hepatocellular carcinoma in a subject in need thereof, nor would the Application be enabled for prevention of chemotherapy resistance, because the Applicant does not provide methods for the prevention of hepatocellular carcinoma and chemotherapy resistances in human cancer patients. Moreover, the instant Specification does not contemplate or provide guidance on expression methods for treatment versus prevention in subjects.
Moreover, despite the instant specification providing an example of treating cells with the cholesterol catabolizing protein, claims 1-2 do not claim administration of the cholesterol catabolizing protein; therefore, Applicant is also not enabled for treatment of hepatocellular carcinoma in claims 1-2. Claims 1-2 are also not enabled for prevention of hepatocellular carcinoma for the reasons discussed above.
State of the prior art: Regarding the prevention of HCC, Erstad teaches that hepatitis B (HBV) is correlated to increased HCC risk; therefore, vaccination is “the most impactful form of HBV prevention”; however, Erstad also teaches that vaccination reduces HCC incidence by 80%, which does not correlate to complete prevention (see, e.g., Erstad, “Prevention Strategies for Hepatocellular Carcinoma”, pg. 261). Along with immunization against HBV for prevention of HCC, Mak teaches that secondary prevention would be risk factors modification, such as “presence of cirrhosis, chronic hepatic necro-inflammation, alcohol use, coinfection with chronic HCV or HIV, metabolic syndrome, and genetic polymorphism” (see, e.g., Mak, “Global Epidemiology, Prevention, and Management of Hepatocellular Carcinoma”, pg. 263). Additionally, Mak teaches that another prevention method would be initiation or continuation of antiviral therapy in patients with chronic HBV; however, Mak teaches that antiviral therapy is mostly beneficial for subjects that have already recovered and received curative treatment for HCC (see, e.g., Mak, “Global Epidemiology, Prevention, and Management of Hepatocellular Carcinoma”, pg. 264). Based on these teachings, the prior art does not teach 100% preventative treatment strategies, especially in individuals that have not previously had HCC.
Relative skill of those in the art: Based on the prior art, the relative skill of those in the art pertaining to prevention of hepatocellular carcinoma, or cancer in general, is low.
Predictability or unpredictability of the art: The level of unpredictability within the artis high, as there are many etiologies for HCC, such as chronic liver disease and cirrhosis, viral infection, alcohol consumption, obesity and metabolic syndromes, autoimmune and genetic disorders, and toxin exposure (see, e.g., Erstad, “Prevention Strategies for Hepatocellular Carcinoma”, pg. 256). Moreover, Mak teaches “pathogenesis for HBV-related HCC is not well established, though is thought to include direct effects from viral DNA integration and translated protein products, as well as indirect effects from secondary hepatic inflammation and fibrosis” (see, e.g., Erstad, “Prevention Strategies for Hepatocellular Carcinoma”, pg. 260). Moreover, diagnosis of HCC can be invasive and/or labor intensive, such as biopsy, ultrasound, quadruple-phase multidetector CT, and dynamic contract-enhanced MRI (see, e.g., Mak, “Global Epidemiology, Prevention, and Management of Hepatocellular Carcinoma”, pg. 272). Additionally, the instant Specification does not contemplate methods for how to prevent HCC, in general and through administration of a cholesterol catabolizing protein. Due to the complex nature of HCC, as well as lack of guidance provided in the instant Specification on how to prevent HCC, the level of unpredictability in the art is high.
Amount of experimentation necessary: Since there are many types of cancers, and the causes are varied and complex, one of ordinary skill in the art would have undue experimentation, especially in regards to hepatocellular carcinoma, in order to understand and determine how to prevent the onset of hepatocellular carcinoma in a patient in need thereof. Moreover, for example, the prior art referenced above shows that it is not possible to prevent cancer since there are many etiologies; therefore, the amount of experimentation to prevent hepatocellular carcinoma is high. Moreover, despite the instant specification and prior art providing an examples pertaining to treatment of hepatocellular carcinoma, claims 1-2 do not claim administration of the cholesterol catabolizing protein; therefore, Applicant is also not enabled for treatment of hepatocellular carcinoma in claims 1-2 since Applicant is merely claiming a protein that occurs naturally within the body and Applicant is not administering anything. Claims 1-2 are also not enabled for prevention of hepatocellular carcinoma for the reasons discussed above.
Claim Rejections - 35 USC § 101, Ineligible Subject Matter
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 1-2 are rejected under 35 U.S.C. 101 because they are drawn to ineligible subject matter (based on the 2019 Revied Patent Subject Matter Eligibility Guidance).
Broadest reasonable interpretation (BRI) of base claim 1: the broadest scope of claim 1 is expressing a cholesterol catabolizing protein in a liver cell.
STEP 1: Is the claim directed to a process, machine, manufacture, or composition of matter?
YES, the claims are directed to a process (method).
STEP 2A: PRONG ONE: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
YES, the claims are considered to be “product of nature” exceptions (i.e., naturally occurring protein(s)). The courts have held that “products of nature” fall under the laws of nature and/or natural phenomenon exceptions.
PRONG TWO: Does the claim recite additional elements that integrate the judicial exception into a practical application?
NO, the additional elements or a combination of elements in the claims does not impose a meaningful limit on the judicial exception. Note that the markedly different characteristics analysis is used to determine if a nature-based product is a “product of nature” exception. Thus, the markedly different characteristic analysis is part of step 2A, i.e., it helps answer the question of whether a claim is directed to an exception, as further explained below.
STEP 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
NO, the claimed invention is directed to a law of nature and/or natural phenomena (i.e., product of nature) without significantly more. Note that the claims must be interpreted under the BRI standard when evaluating for a marked difference, Under BRI, the claims broadly read on cholesterol catabolizing proteins, which is a protein that exists within the body, and Applicant is not administering anything to treat hepatocellular carcinoma. Based on the BRI, Applicant is simply claiming a natural phenomenon that occurs within the body and Applicant is not administering anything. Luoma (Cytochrome P450 – physiological key factor against cholesterol accumulation and the atherosclerotic vascular process; 2007) teaches that multiple cytochrome P450 enzymes, which are naturally occurring, “catabolize cholesterol to oxysterols and other metabolites” (see, e.g., Luoma, Introduction, pg. 359). More specifically, Luoma teaches that CYP7A1, CYP27A1, CYP46A1, and CYP3A4 are cytochrome P450 enzymes responsible for catabolizing cholesterol to oxysterols (see, e.g., Luoma, “P450 enzymes, oxysterols, and bile acids”, pgs. 360-361). Furthermore, Honkanen (US 2020/0179452; Date of Publication: June 11, 2020 – cited in the IDS filed on 02/26/2024) teaches the expression of a cholesterol catabolizing protein(s) within Hep3B cells (i.e., liver cells) (see, e.g., Honkanen, [0084]).Therefore, there is no indication that the claimed composition has any markedly different characteristic (e.g., structure, function, phenotype, etc.) that is different than what is found in nature. Thus, it appears that the Applicant is claiming a natural phenomenon for claims 1-2 because Applicant is claiming a protein that exists within the body and Applicant is not administering anything.
Therefore, the claims are interpreted under the BRI standard, wherein the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim does not recite any additional elements.
Therefore, claims 1-2 are considered products of nature which are directed to judicially recognized exceptions without amounting to significantly more from what occurs in a nature and thus, are not eligible under 35 U.S.C. 101.
Claim Rejections - 35 USC § 102, Anticipation
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Honkanen (US 2020/0179452; Date of Publication: June 11, 2020 – cited in the IDS filed on 02/26/2024).
Honkanen’s general disclosure relates to methods of administering to subjects “one or more mammalian cells modified to express at least one sterol degrading enzyme derived from a bacterium” (see, e.g., Honkanen, abstract). Moreover, Honkanen discloses that the composition containing the sterol degrading enzyme is useful in lowering cholesterol levels in a subject in need thereof” (see, e.g., Honkanen, abstract). Honkanen discloses “methods for modifying a mammalian cell with nucleic acid compositions that enable and/or promote expression of one or more proteins useful in degrading a sterol” (see, e.g., Honkanen, [0009), wherein the proteins are enzymes capable of altering a sterol, such as “cholesterol dehydrogenase (CholD), 3-ketosteroid Δ1-dehydrogenase (Δ1-KstD), anoxic cholesterol metabolism B enzyme (acmB), 3-ketosteroid 9α-hydroxylase (KshAB), 3β-hydroxysteroid dehydrogenase 2 (HSD2), and P450-ferredoxin reductase-ferredoxin fusion protein (P450-FdxR-Fdx)” (see, e.g., Honkanen, [0010]). Furthermore, Honkanen discloses the expression of the sterol degrading enzyme(s) in the mitochondria of liver cells (see, e.g., Honkanen, [0083]-[0086]).
Regarding claims 1 and 8 pertaining to expression of a cholesterol catabolizing protein, Honkanen teaches the expression of a cholesterol catabolizing protein(s) within Hep3B cells (i.e., liver cancer cells) (see, e.g., Honkanen, [0084]). Independent claims 1 and 8 are directed to treating or preventing hepatocellular carcinoma; however, claims 1 and 8 are not directed to a specific patient population with the phase “in need thereof”. Moreover, in regards to preventing hepatocellular carcinoma, anyone would want to prevent carcinoma and a population is not claimed; therefore, since Honkanen teaches the same method steps of expressing a cholesterol catabolizing protein then the method taught by Honkanen anticipates prevention of hepatocellular carcinoma. Furthermore, the Hep3B cell line is a hepatocellular carcinoma liver cell line; therefore, administration of the cholesterol catabolizing protein to Hep3B would be administering the protein to a subject in need thereof, thereby treating the hepatocellular carcinoma cell line. Additionally, the reduction in the growth rate of the liver cell would be inherent. Honkanen teaches the same method of administering a cholesterol catabolizing protein to a liver cell. Therefore, the prior art teaches administering the same composition (i.e., cholesterol catabolizing protein(s)) to the same cells (i.e., Hep3B liver cells), which would inherently lead to the same effect of reducing the growth rate of the liver cells since the inherent properties exhibited by the cholesterol catabolizing protein(s) would be present within the applied composition (see, e.g., MPEP 2112.02).
Regarding claims 2 and 8 pertaining to expression in the mitochondrion of the liver cell, Honkanen teaches that the cholesterol catabolizing protein(s) were constructed with a mitochondrial targeting sequence in order to localize to the mitochondria within Hep3B cells (see, e.g., Honkanen, [0083]-[0086], [0166], [0296]-[0298]).
Claim Rejections - 35 USC § 103, Obviousness
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claims 3-7 and 9-14 are rejected under 35 U.S.C. 103 as being unpatentable over Honkanen as applied to claims 1-2 and 8 above, and further in view of Grazie (Chemotherapy for hepatocellular carcinoma: The present and future; 2017).
The teachings of Honkanen are discussed above as it pertains expressing a cholesterol catabolizing protein in a liver cell.
Regarding claim 4 and 11 pertaining to the catabolizing protein, Honkanen teaches that the catabolizing protein is P450-ferredoxin reductase-ferredoxin fusion protein (P450-FdxR-Fdx)” (see, e.g., Honkanen, [0010]).
Regarding claims 7 and 14 pertaining to entering the apoptotic pathway, the liver cell entering the apoptotic pathway after expressing the cholesterol catabolizing protein(s) would be inherent. Honkanen teaches the same method of expressing a cholesterol catabolizing protein within a liver cell (see, e.g., Honkanen, [0084]). Therefore, the prior art teaches administering the same composition (i.e., cholesterol catabolizing protein) to the same subject (i.e., liver cells) which would inherently lead to the same effect of the liver cell entering the apoptotic pathway since the inherent properties exhibited by the cholesterol catabolizing protein would be present within the applied composition (see, e.g., MPEP 2112.02).
However, Honkanen does not teach: wherein the liver cell is contacted with at least one chemotherapeutic compound, and the chemotherapeutic compound is administered to the subject before, after, or while the cell is expressing the one or more cholesterol catabolizing protein (claims 3 and 10); or wherein the chemotherapeutic agent is selected from Sorafenib and Lenvatinib (claims 5 and 12); or wherein the subject is administered a chemotherapeutic compound (claim 9); or wherein the method prevents or reduces the likelihood of a mammalian cell being resistant to chemotherapy (claims 6 and 13).
Grazie’s general disclosure relates to a review of chemotherapeutic therapies for hepatocellular carcinoma (see, e.g., Grazie, abstract). Moreover, Grazie teaches that “sorafenib is the only standard treatment available for advanced HCC” (see, e.g., Grazie, abstract). Additionally, Grazie teaches “To develop novel systemic therapies for HCC, sorafenib was also evaluated as second-line therapy after fluoropyrimidine plus platinum-based chemotherapy[33]: The resulting disease control rate of 58.3%, with overall survival and progression-free survival of 7.1 and 2.3 mo, respectively, without increased incidence of adverse events, suggests a modest efficacy of sorafenib as second-line treatment after other systemic therapies” (see, e.g., Grazie, “Sorafenib”, pg. 909).
Regarding claims 3, 5, 9, 10, and 12 pertaining to administration of a chemotherapy to the subject, Grazie teaches that Sorafenib is the only standard treatment administered to patients with hepatocellular carcinoma (see, e.g., Grazie, abstract).
Regarding claims 6 and 13 pertaining to reducing the likelihood of the cell being resistant to chemotherapy, the combined prior art of Honkanen and Grazie teach the instantly claimed method of administering a cholesterol catabolizing protein (see, e.g., Honkanen, [0084]) and a chemotherapy (see, e.g., Grazie, abstract) for hepatocellular carcinoma. Therefore, the prior art teaches administering the same composition (i.e., cholesterol catabolizing protein and chemotherapy) to the same subject (i.e., liver cells) which would inherently lead to the same effect of reducing resistance to chemotherapy since the inherent properties exhibited by the cholesterol catabolizing protein and chemotherapy would be present within the applied composition (see, e.g., MPEP 2112.02).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer Honkanen’s cholesterol catabolizing protein in combination with a chemotherapeutic, such as Sorafenib, for hepatocellular carcinoma, as taught by Grazie. One would have been motivated to do so because Grazie teaches “The action of sorafenib is expressed on various molecular targets involved in the mechanism of tumor growth and angiogenesis, leading to their inhibition” (see, e.g., Grazie, “Sorafenib”, pg. 908). Moreover, Grazie teaches “The SHARP trial compared Sorafenib treatment (400 mg twice a day) to placebo among 602 patients, showing a significant difference in overall survival (10.7 mo vs 7.9 mo, P < 0.001), time to radiologic progression (5.5 mo vs 2.8 mo, P < 0.001) and disease control rate (43% vs 32%, P = 0.002)” (see, e.g., Grazie, “Sorafenib”, pg. 909). Additionally, Grazie teaches “To develop novel systemic therapies for HCC, sorafenib was also evaluated as second-line therapy after fluoropyrimidine plus platinum-based chemotherapy[33]: The resulting disease control rate of 58.3%, with overall survival and progression-free survival of 7.1 and 2.3 mo, respectively, without increased incidence of adverse events, suggests a modest efficacy of sorafenib as second-line treatment after other systemic therapies” (see, e.g., Grazie, “Sorafenib”, pg. 909). Moreover, Honkanen teaches the expression of a cholesterol catabolizing protein within Hep3B cells (i.e., liver cells) (see, e.g., Honkanen, [0084]); therefore, since Honkanen teaches the same claimed method steps of expressing a cholesterol catabolizing protein within the same claimed subject then the cholesterol catabolizing protein can treat or prevent hepatocellular carcinoma. Based on the teachings of Honkanen and Grazie, it would have been obvious to add Sorafenib to the administered composition due to the additive treatment of hepatocellular carcinoma (see, e.g., In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). One of ordinary skill in the art would have expected success because Honkanen and Grazie both teach treatment of diseases
Conclusion
Claims 1-14 are rejected.
No claims are allowed.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE IANNUZO whose telephone number is (703)756-5559. The examiner can normally be reached Mon - Fri: 8:30-6:00 EST.
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/NATALIE IANNUZO/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653