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 .
Claim Status
Claims 1-16 are pending. Claims 1-16 are under examination and discussed in this Office action.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 2nd, 2022 and January 13th, 2025 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because of the following informalities:
Table 1 on page 7 contains nucleotide sequences, however, the sequences are not identified by corresponding SEQ ID Nos.
Appropriate correction is required.
Claim Objections
Claim 16 is objected to because of the following informalities: the listing of tumor types lacks a comma between “thyroid carcinoma (THCA)” and “and uterine corpus endometrial carcinoma (UCEC)”. In addition, there is no space between “uterine corpus endometrial carcinoma” and “(UCEC)”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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 3 and 9-16 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.
In making a determination of whether the application complies with the written
description requirement under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, it is
necessary to understand what Applicant is claiming and what Applicant has possession
of. To satisfy the written description requirement, a patent specification must describe
the claimed invention in sufficient detail that one skilled in the art can reasonably
conclude that the inventor had possession of the claimed invention. See, e.g., Moba,
B.V, v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed.
Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was “ready for patenting” such as by the 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. See, e.g., Pfaff v. Wells Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991). See MPEP § 2163.
Claim 3 recites “[a]n application of the vector containing the target sequence that targets and interferes with Helz2 according to claim 1 in preparation of biological agents for inhibiting expression of Helz2.” The claim as written appears to embrace the use of the claimed vector in the preparation of unspecified biological agents for inhibiting Helz2 expression. However, the “application of the vector” and “biological agents” are not defined or described in the claim.
Regarding claim 3, the specification does not clearly describe or define the full scope of the claimed application of the vector. At paragraph, [0059], it is described that “Helz2-Cas9-KO mice and shRNA interference- mediated Helz2-targeting therapy were conducted with tumor-bearing wild-type mice.” Paragraph [0053] lists various types of vectors, including “lentiviral vector complex, adenovirus, adeno-associated virus, N- acetylgalactosamine (GalNAc), liposomes (LNPs), polymers and oncolytic viruses.” These cited descriptions are limited to specific examples and contexts. It is broadly drawn to an “application of the vector” in preparation of biological agents for inhibiting Helz2 expression without limiting the application to the specific therapeutic uses, delivery systems, or experimental conditions in the specification. The specification also states that the present disclosure further provides “an application of the vector containing the sequence targeting Helz2 in preparation of biological agents for inhibiting expression of Helz2” [0057]. This cited description merely repeats the claim language in general terms and does not provide structural or functional limitations that would clarify the scope of the claimed application. Therefore, it cannot be said that there is a definitive description of an application of the vector as claimed.
Additionally, it does not define or describe what “biological agents” are being prepared. Claim 3 is broadly drawn to preparation of any biological agent for inhibiting expression of Helz2. The specification describes vectors containing a target sequence that targets and interferes with Helz2 (SEQ ID No: 5-7), including lentiviral vectors and other biologically acceptable gene vectors [0052-0056]. However, the specification does not define what constitutes a “biological agent” beyond these examples, nor does it describe biological agents having structural characteristics correlated with the function of inhibiting Helz2 expression.
Regarding claims 9-16, claim 9 recites “[a] drug for treating or preventing a tumor, comprising: a product targeting an Helz2 gene or targeting an expression of the Helz2 gene.” The claim as written appears to embrace any “drug” that targets the Helz2 gene or its expression, without limitation as to structure, mechanism, or formulation. The claim or specification does not provide any species or structure feature that would allow one of ordinary skill in the art to recognize the boundaries of the claimed “drug”.
Regarding claim 9, the specification states the present disclosure provides “a drug for treating or preventing a tumor. The drug includes a product targeting an Helz2 gene or targeting an expression of the Helz2 gene” [0017]. Paragraph [0058] states that the drug “contains a Helz2-targeting sequence or its expressed product” These cited descriptions merely repeat the language of the claim in broad language and does not provide a description any drug formulation. It is also noted that claim 10-16 also suffer from the same issue of not providing adequate description of the drug.
Regarding claim 10, it is noted that the sequences of SEQ ID Nos 5-6 do provide structure to the target sequence however, this limitation does not further define the structure of the drug product as claimed.
Claims 11-16 are included here because they depend from claim 9 and do not provide any additional structure to the drug as claimed.
In conclusion, there are no representative species in the art and the species disclosed in the specification are not sufficient to represent the full breadth of the claimed invention according to claims 3, and 9-16. Furthermore, a structure-function correlation is not shown in the specification or the art to account for the high degree of variability of the drugs as laid forth in the instant claims. Thus, claims 3, and 9-16 are rejected under 35 U.S.C. 112(a) for failing to comply with the written description requirement.
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 and 7 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: specific procedural steps for preparing or screening the drug using the Helz2 systematic knockout homozygous mouse model, including administering a drug to the mouse model, evaluating the efficiency of the drug, and determining the screening criteria.
Claim 6 recites “[a] method for preparing or screening a drug for treating or preventing a tumor, comprising: using the Helz2 systemic knockout homozygous mouse model according to claim 4 in preparation or screening of the drug.” The claim as written appears to embrace a method of preparing or screening a drug using the Helz2 knockout mouse model. However, the claim does not recite any specific operative steps describing how the preparation or screening is performed.
Regarding claim 6, the specification does not clearly describe or define a method of preparing or screening a drug using the Helz2 systematic knockout homozygous mouse model. At paragraph [0046], it is stated that the present disclosure provides “an application of an Helz2 systemic knockout homozygous mouse model in preparation or screening of anti-tumor drugs and/or drugs for preventing tumors.” This cited statement is general and does not provide a description of the specific procedural steps required to carry out such preparation or screening.
Turning to the examples, examples 1-6 describe tumor bearing experiments comparing wild-type mice and Helz2 knockout mice after inoculation with various tumor cell lines [0060] – [0077]. These examples demonstrate that Helz2 knockout mice can have prolonged survival and resistance to tumor growth. However, these examples do not describe screening of any drugs, administering compounds to Helz2 knockout mice for evaluation, determining efficiency of the drugs, or establish criteria for identifying the drug as effective. Similarly, examples 7-9 describe lentiviral shRNA-mediated targeting of Helz2 in tumor cells and treatment of tumor bearing wild-type mice [0078] – [0084], but do not describe drug screening or preparation process using the Helz2 knockout mouse model as required by claim 6.
Claim 7 further recites, “[t]he preparation or screening of the drug comprises: screening of a drug target, screening of the drug, pharmacodynamic evaluation of the drug and safety evaluation of the drug.” Claim 7 expands the method to include multiple drug categories for drug development. However, it does not describe how drug target screening is performed, how drugs are screened, how pharmacodynamic evaluation is conducted, or how safely evaluation is performed within the context of the claimed method.
Regarding claim 7, the specification also lists the activities in general broad manner [0046]. The specification does not provide corresponding methodological details for conducting the recited screening and evaluating steps. There’s no description of dosage, control groups, pharmacodynamic endpoints, toxicity testing, statistical criteria, or experimental designs.
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.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Yoshino (Protection Against High-Fat Diet-Induced Obesity in Helz2-Deficient Male Mice Due to Enhanced Expression of Hepatic Leptin Receptor, published online July 8th, 2014; cited on the IDS filed January 13th, 2025), in view of Doyle (The construction of transgenic and gene knockout/knockin mouse models of human disease, Springer, Volume 21, pages 327–349, (2012)).
Regarding instant claim 4, Yoshino teaches a method for establishing a Helz2 knockout mouse model. Specifically, Yoshino teaches generating Helz2 knockout (KO) by constructing a targeting vector in which a neomycin cassette (NEO) was substituted for exons 1-6 of the mouse Helz2 gene. Yoshino further teaches that chimera mice were generated using a standard homologous recombination technique and were backcrossed with C57BL/6 mice to obtain F1 heterozygous KO mice, which were then interbred to obtain Herz2 KO mice (p. 3460, right column, para 2).
Yoshino does not directly teach performing the Helz2 knockout on fertilized mouse eggs using a CRISPR/Cas9 technique with an sgRNA sequence, nor does Yoshino describe microinjection of CRISPR/Cas9 components into fertilized eggs.
Doyle, in a reasonably pertinent field, teaches a method of generating knockout mice through embryo manipulation and subsequent breeding. Doyle teaches that gene-specific modifications may be introduced into embryonic step (ES) cells using a DNA targeting construct containing regions of homology of the gene of interest, followed by selection of homologous recombination events (p. 337; fig. 3). Doyle further teaches that targeted ES cell clones are transferred into blastocyst embryos, which are implanted into surrogate females to generate chimeric founder mice. These founders are then bred to obtain mice carrying the targeted null allele, resulting in a Mendelian inheritable knockout strain (p. 337; fig. 3).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the homologous recombination-based ES cell targeting approach of Yoshino by applying an alternative, known genome editing technique capable of generating targeted gene disruptions at the embryo stage, such as CRISPR/Cas9 technique of fertilized mouse eggs via microinjection in order to generate a germline transmissible Helz2 knockout mouse.
Conclusion
Claim 5 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 1, 2, and 8 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nura Choudhury whose telephone number is (571)272-6148. The examiner can normally be reached M-F, 9-5 ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at 571-272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NURA M. CHOUDHURY/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683