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
Applicant’s election without traverse of Invention I, claims 1-6 in the reply filed on February 4, 2026 is acknowledged.
Applicant’s election without traverse of species: small molecule compound, in the reply filed on February 4, 2026 is also acknowledged.
Claim 7 has been canceled.
Claim 8 has been added.
Claims 1-6 and 8 are pending.
Claim 8 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions or species, there being no allowable generic or linking claim.
Claims 1-6 are pending and under consideration.
Priority
Acknowledgement is made that this application claims priority to a Chinese Patent Application No. 202411085129.7 filed August 8, 2024.
Certified copies of foreign priority applications have been received as required by 37 CFR 1.55.
Information Disclosure Statement
No Information Disclosure Statement (IDS) has been filed in this application. Applicant is reminded that each individual associated with the filing and prosecution of a patent application has a duty of candor and good faith in dealing with the U.S. Patent and Trademark Office, which includes a duty to disclose to the Office all information known to that individual to be material to patentability (see 37 C.F.R. §1.56).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-6 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “using the ITIH1 for treating hepatocellular carcinoma”, but the claim does not recite any method step of using the ITIH1. Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See MPEP 2173.05 (q).
Claim 1 recites “preparing a drug by using the ITIH1 for treating hepatocellular carcinoma” which renders the claim indefinite. It is unclear if the limitation is drawn to preparing a drug which is for treating hepatocellular carcinoma, or using the ITIH1 to treat hepatocellular carcinoma which somehow prepared the drug.
Claim 4 recites “the ITIH1 is used to…”, but the claim does not have any method steps of using the ITIH1. Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See MPEP 2173.05 (q).
Claim 6 recites “by using the substance…”, but the claim does not have any method steps of using the substance. Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See MPEP 2173.05 (q).
Claim 6 recites “wherein the target is one of an up-regulation target and an activation target” which renders the claim indefinite. It is unclear if the limitation is drawn to the target is a target up-regulated or activated by the substance, or is a target up-regulated or activated by components in ITIH1 signaling pathway.
Claims 2, 3 and 5 are also rejected because these claims depend on the rejected claims.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to an application method of inter-alpha-trypsin inhibitor heavy chain 1 (ITIH1), comprising: preparing a drug by using the ITIH1 for treating hepatocellular carcinoma (HCC). The claims encompass a broadly claimed: “a reagent for increasing an expression of the ITIH1” or “a substance taking one of an ITIH1 protein and an ITIH1 gene as a target”. Given Broadest Reasonable Interpretation (BRI), the reagents and substances can have different structures (e.g. small molecule compound (the elected species), peptide, lipid, carbohydrate, antibody, protein, oligonucleotide, genome editing system). These reagents/substances can vary significantly, have physical and/or chemical properties. In addition, these reagents/substances may target different genes in ITIH1 signaling pathway, such as SMAD3, METTL3, or YTHDF2. The specification teaches only ITIH1 protein which has anti-tumor activity in a in vivo HCC model (Results 2.4, [00211-00213]). Thus, the specification lacks written description support for the broadly claimed application methods which encompass unlimited compounds, including unlimited small molecule compounds (the elected species) for the claimed invention.
Vas-Gath, Inc. v" Mahurkar, 19 USPQ2d 1111, makes clear that "to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed".
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of afunctional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., binding to antigen, high affinity, neutralization activity, competing with a reference antibody for binding), “[claiming antibodies with specific properties, e.g., an antibody that binds to human TNF-a with A2 specificity, can result in a claim that does not meet written description even if the human TNF-a protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
Regarding “a reagent for increasing an expression of the ITIH1” or “a substance taking one of an ITIH1 protein and an ITIH1 gene as a target”, the specification teaches only ITIH1 protein which has anti-tumor activity in a in vivo HCC model (Results 2.4, [00211-00213]). The specification also discloses a few silencing RNAs can indirectly increase an expression of ITHI1. For example, short hairpin (sh)-SMAD3 (Fig. 2B), sh-METTL3 (Fig. 2C and Fig. 3A) and siRNAs to YTHDF2 (Fig. 6C) can lead to an increased expression of ITIH1. However, the therapeutic activity of these compounds to HCC is not shown. It is well known in the art, the therapeutic activity for a compound for a cancer is highly unpredictable. Hou (Hou et al., Molecular Cancer (2019) 18: 163, Publication Year: 2019) teaches that over-expression of YTHDF2 could suppress HCC growth, but YTHDF2 deficiency promotes HCC growth, vasculature remodeling and metastasis (the bridging paragraph of cols. 1-2 on page 4). YTHDF2 silencing by shRNA facilitated tumor growth and metastasis in HCC model in vivo (Figs. 2C-2E, and the bridging paragraph of cols. 1-2 on page 4). Thus, even though YTHDF2 silencing RNA can increase ITIH1 expression (based on the results of the instant specification), it may not be suitable to be used as a drug to treat HCC.
Regarding the elected species: small molecule compounds for increasing an expression of the ITIH1, the specification does not disclose any small molecule compound with recited regulating property and can be used to treat HCC.
In addition, the claims identify the reagents/substances by functions only, where the function is to:
treat hepatocellular carcinoma
increase expression of the ITIH1
influence metastasis of hepatocellular carcinoma
competitive bind to an integrin subunit beta 1 (IGTB1) and integrin subunit alpha 5 (ITGA5) complex
inhibit integrin and focal adhesion kinase (FAK) signaling pathway
increase expression of the ITIH1 regulated by TGF-β and N6-methyladenosine modification
activate ITIH1
However, the instant specification has not provided a sufficient description about the correlation between the recited functions and the structure of the reagents, or substances. Based on the specification and prior art, one of ordinary skilled in the art would not be able to “visualize or recognize” other members of the genus, excepted the one (ITIH1 protein) described in the specification with the recited functions. Based on the specification and prior art, one of ordinary skilled in the art would not be able to “visualize or recognize” any small molecule compound (the elected species) with the recited properties and functions. A definition by function does not suffice to define the genus because it is only an indication of what the recited reagents/compounds/drugs do, rather than what they are.
Furthermore, the written description provision of 35 USC § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai
Pharmaceutical Co. Ltd., 18 USPQ2d 1016. The Guidelines for Examination of Patent
Applications under the 35 USC §112 paragraph 1, "Revision 1" of Written Description
Requirement (66 FR 1099-1111, March 25, 2008) state, "[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the Applicant was in possession of the claimed invention (Id. At 1104). Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was "ready for patenting" by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the
Applicant described distinguishing identifying characteristics sufficient to show that
Applicant were in possession of the claimed invention at the time the application was filed.
Taken together, the instant specification has not provided a sufficient description showing possession of the necessary functional characteristics coupled with a known or disclosed correlation between functions and the structure of the recited reagents and substances by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed invention.
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 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Qian (Qian et al., Kaohsiung J Med Sci., 2022; 38: 437-446, Publication Date: 01/25/2022).
Qian teaches Lysine demethylase 5C (KDM5C) is a member of the KDM family of demethylases and has been reported as a cancer driver. KDM5C is highly expressed in liver hepatocellular carcinoma (LIHC) and associated with poor patient prognosis. High expression of KDM5C was detected in acquired LIHC cell lines. Downregulation of KDM5C weakened proliferation, migration, invasiveness, and resistance to death of the LIHC cells in vitro, and it reduced growth of the xenograft tumors in nude mice (Abstract).
Qian teaches that ITIH genes are downregulated in multiple types of human solid tumors, indicating they might serve as tumor-suppressing genes (page 443, col. 2). Cancer patients with high expression of ITIH1 have better survival rates than those with low expression (Fig. 3C).
Qian teaches that ITIH1 shows negative correlation with KDM5C (page 443, col. 1; and Fig. 3D).
Qian teaches that KDM5C reduce H3K4me1 level to suppress ITIH1 transcription in LIHC cells (Fig. 4A); mRNA level of ITIH1 was significantly increased upon KDM5C silencing by short hairpin (sh)-RNA (Fig. 4B); downregulation of KDM5C enhanced the protein levels of ITIH1 and H3Kme1 in LIHC cells (Fig. 4E). Thus, shRNA of KDM5C would read on “a reagent for increasing an expression of the ITIH1”.
Qian teaches that sh-KDM5C slows the proliferation of LIHC cancer cells (Figs. 5C and 5D).
Qian teaches that the migration and invasive ability of cells suppressed by sh-KDM5C were recovered by sh-ITIH1 (Fig. 5G and Fig. 5G). These results indicate that the anti-tumor activity of sh-KDM5C in LIHC depends on the induced expression of ITIH1.
Qian teaches that downregulation of KDM5C inhibits growth of LIHC xenograft tumors in vivo. the growth rate of the xenograft tumors was significantly reduced by sh-KDM5C versus sh-NC (Figure 6A). After 4 weeks, the mice were euthanized to collect the tumors. The weight of the xenograft tumors was reduced by sh-KDM5C as well (Figure 6B). Tumor tissues were collected for IHC, and the staining intensity (protein level) of ITIH1 was enhanced, whereas the staining intensity of the proliferation-marker Ki67 was reduced in the tumor tissues with stable KDM5C downregulation (Figure 6C). See § 3.6 on page 445.
Qian teaches that reduced expression of ITIH1 mediated by KDM5C likely led to PI3K/AKT activation that resulted in augmented progression of LIHC. Moreover, the oncogenic role of KDM5C and the direct tumor-suppressive function of ITIH1 were confirmed in LIHC (the last paragraph of the article).
Although Qian does not explicitly teach making a drug to treat hepatocellular carcinoma with an reagent for increasing an expression of the ITIH1, it would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to prepare a drug comprising sh-KDM5C which can induce expression of ITIH1 to treat LIHC, because Qian shows the anti-tumor activity of sh-KDM5C in both in vitro assay and in vivo for LIHC, Qian also shows that increased ITIH1 expression is important for the antitumor activity of sh-KDM5C. One of ordinary skill in the art would have a reasonable expectation that a drug comprising sh-KDM5C would be able to induce ITIH1 expression and treat ITIH1 based on the results of Qian. The motivation would have been to develop a new drug for LIHC treatment.
Regarding claim 4, as evidenced by [00216] of the instant specification, ITIH1 protein has the property of functioning as a novel ligand for ITGB1/ITGA5 and competes with FN for binding to IGTB1. As evidenced by [00218] of the instant specification, ITIH1 protein has the property of inhibiting HCC metastasis by suppressing the integrin/FAK signaling pathway. Thus, the ITIH1 protein induced by the sh-KDM5C would have the same property and function as exampled in the instant specification.
Regarding claim 5, as evidenced by Results 2.1 and 2.2 of the instant specification, all endogenous ITIH1 gene would be regulated by TGF-β stimulation and N6-methyladenosine (m6A) modification. The ITIH1 gene/protein induced by the sh-KDM5C, which are endogenous ITIH1, would also be regulated by TGF-β stimulation and N6-methyladenosine (m6A) modification.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
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, Samira Jean-Louis can be reached at (571)270-3503. 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.
/CHENG LU/ Examiner, Art Unit 1642