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
Claims 1-16 are pending.
Applicant’s election without traverse of Group I, claims 1-12 in the reply filed on 08/27/2026 is acknowledged.
Claim 13-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 08/27/2026.
Claims 1-12 have been examined on their merits.
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.
Claim 12 is 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 12 contains the trademark/trade name “biosilk”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a silk biological scaffold and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-7 are rejected under 35 U.S.C. 102(a)(1) or 35 U.S.C. 102(a)(1) as being anticipated by Li et al. (US20060172416A1, on IDS 06/28/2023) as evidenced by Pan et al. (International Journal of Medical Sciences, 2015, on IDS 06/28/2023).
Regarding claim 1, Li discloses an immortalized (transformed) cell line of human hepatic stellate (HSCs) (claim 1; paragraph [0048]). Li disclose that the cells are immortalized with hTERT or SV40 large T-antigen (SV40LT) (claims 24 and 25). It is noted that the term “or” is understood to be inclusive, and therefore, a person of ordinary skill in the art would have at once envisioned a combination of hTERT and SV40 large T-antigen from the disclosure of Li (see MPEP 2131.02). While Li is silent as to whether the cells express the marker PDGFR-β, as evidenced by Pan, PDGFR-β is a known HSC marker (Immunofluorescence staining for the protein expression of HSC markers in HSC-Li cells, [252) which is known to be expressed in at least SV40LT transformed (Figure 4, [252). Therefore, the HSCs as disclosed by Li are considered to be PDGFR-β absent evidence to the contrary.
Regarding claims 2-4, overexpression of α-SMA is a property of immortalized HSAs. As further evidenced by Pan, SV40LT transformed HSCs strongly (overexpress) α-SMA (Immunofluorescence staining for the protein expression of HSC markers in HSC-Li cells, p252; Fig. 4, p252). Therefore, the HSCs disclosed by Li are considered to overexpress α-SMA absent evidence to the contrary. Moreover, as evidenced by Pan, α-SMA itself is a HAS marker (discussion, p253).
Regarding claim 5, the claim is drawn to a cell, not a method and does not require testing expression levels against LX-2 cell (which are noted are a well-known immortalized cell line). Additionally, expression of an HSC marker (which is noted is unlimited in the claim) is an inherent property of HSCs immortalized by introduction of hTERT and SV40LT. Therefore, since Li discloses these cells, they would naturally express “at least 1.5” an HSC marker compared to a LX-2 cell line when set to 1.
Regarding claim 6, increased expression (which is noted is undefined) of the claimed markers is an inherent property of hepatocytes immortalized by introduction of hTERT and SV40LT (see instant Fig. 3c, other cell lines including LX-2 cells express these markers. Therefore, the transformed cells of Li are considered to have “increased expression” of COL-4A1 absent evidence to the contrary.
Regarding claim 7, it is well-known in the art that HSCs are the primary drivers of liver fibrosis. See also as above, as evidenced by Pan, SV40LT transformed HSCs strongly (overexpress) α-SMA (Immunofluorescence staining for the protein expression of HSC markers in HSC-Li cells, p252; Fig. 4, p252), which the instant specification indicates is a marker of liver fibrosis (he degree of fibrosis progress of the hepatic stellate cell lines was confirmed through the expression levels of smooth muscle actin alpha (α-SMA), paragraph [00287]).
Therefore, Li anticipates the invention as claimed.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (US20060172416A1, on IDS 06/28/2023) in view of Wei et al. (Journal of Biomedical Materials Research A, 2018, on IDS 06/28/2023)
Li anticipates claim 1 as discussed above.
Regarding claims 8 and 10-12, the instant specification states, “The term ‘artificial liver construct’ as used herein refers to a 3D cell mass that simulates human liver functions. The artificial liver construct may be a liver spheroid formed by direct binding of hepatic stellate cells and hepatic cells. In addition, the artificial liver construct may be a 3D liver analog formed by 3D culture of hepatic stellate cells and hepatic cells with a scaffold (support)” (paragraph [0050]).
A person of ordinary skill in the art would have been motivated to formulate the cell line of Pan into an artificial liver construct because Wei teaches that 3D cocultures if primary hepatocytes and stellate cells in silk scaffold improves hepatic morphology and functionality in vitro (Title, Abstract, p2171). As taught by Wei, bioartifical livers recapitulate hepatic phenotype and functionality in vivo,’ improves the efficiency of bioartificial liver, drug discovery, or even transplantation therapy; and contribute to the construction of micro-organoid tissue of liver but also potentially provide a robust tool for drug metabolism evaluation in vitro (Title, Abstract, p2171). They would have been motivated to use a silk scaffold because Wei teaches that silk scaffolds incorporated extracellular matrix provided a suitable microenvironment for maintaining the viability, morphology and gene expression of the primary hepatocyte in vitro (Abstract, p2171). Furthermore, because Wei demonstrates making that artificial liver constructs (which also form spheroids) (Results, p2174; Figs. 1-3) a person of ordinary skill in the art could have adapter the cell line of Pan to am artificial liver construct in a biosilk scaffold as claimed with predictable results and a reasonable expectation of success.
Regarding claim 9, Pan teaches the HSCs are primary cell derived (Abstract, p248).
Therefore, the combined teachings of Pan and Wei render the invention unpatentable as claimed.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH (PAUL) MIANO whose telephone number is (571)272-0341. The examiner can normally be reached Mon-Fri from 8:30am to 5:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Doug) Schultz can be reached at (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JOSEPH PAUL MIANO/Examiner, Art Unit 1631
