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
This Office Action is a reply to Applicant’s Election (Response to Restriction Requirement) filed August 27, 2025.
Claims 1, 2, 4-11, 13-16 and 18-28 are pending in the instant application.
Election/Restrictions
Applicant’s election (without traverse) of Group I (claims 1, 2, 4-9, 27 and 28) in the reply filed on August 27, 2025 is acknowledged. Applicant’s further election of SEQ ID NO: 1 as the COPS3 target sequence in the reply filed on August 27, 2025 is also acknowledged.
Claims 10, 11, 13-16 and 18-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on August 27, 2025.
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, claims 1, 2, 4-9, 27 and 28 have been examined on the merits as detailed below:
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed September 16, 2022 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed June 21, 2022 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Drawings
The Drawings filed June 21, 2022 are acknowledged and have been accepted by the Examiner.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on EP 19217769.9 filed 12/19/2019. The certified copy has been placed in the file.
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.
Claim 8 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 pre-AIA the applicant regards as the invention.
Claim 8 is dependent on claim 3. Claim 3 was canceled in Applicant’s Preliminary Amendment filed December 27, 2022. Because claim 8 is dependent on a canceled claim, the metes and bounds of claim 8 cannot be determined. See MPEP 608.01(n), for further explanation. Claim 8 has not been further considered on the merits.
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.
Claim 28 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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. This is an enablement rejection.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988).
Wands states on page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The claim is drawn to a method of treating or prevention of a disease in a subject suffering from or susceptible to the disease, said method comprising administering a therapeutically or prophylactically effective amount of a nucleic acid molecule of 12 to 30 nucleotides in length comprising a contiguous nucleotide sequence of at least 12 nucleotides which is 90% complementary to a mammalian COPS3 target sequence, wherein the nucleic acid molecule is capable of inhibiting the expression of COPS3 mRNA to the subject. The invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
It should be made clear that, the enabling specification must teach those skilled in the art to make and use the full scope of the claimed invention without undue experimentation. “Although not explicitly stated in section 112, to be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without "undue experimentation." Vaeck, 947 F.2d at 495, 20 USPQ2d at 1444; Wands, 858 F.2d at 736-37, 8 USPQ2d at 1404; In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (the first paragraph of section 112 requires that the scope of protection sought in a claim bear a reasonable correlation to the scope of enablement provided by the specification).” In re Wright (CAFC) 27 USPQ2d 1510 at 1513. Although a working example is not required to enable an invention, the skilled artisan must be able to practice the claimed invention without undue experimentation. See also, MPEP §2164.02, which states in part: The specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970). Lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.
The prior art does not teach a method of prevention of a disease in a subject suffering from or susceptible to the disease, said method comprising administering a prophylactically effective amount of a nucleic acid molecule of 12 to 30 nucleotides in length comprising a contiguous nucleotide sequence of at least 12 nucleotides which is 90% complementary to a mammalian COPS3 target sequence, wherein the nucleic acid molecule is capable of inhibiting the expression of COPS3 mRNA to the subject.
The present description provides examples wherein the reduction of COPS3 mRNA, HBV intracellular DNA and cccDNA in HBV infected primary human hepatocytes (PHH) cells in culture resulting from siRNA treatment; and reduction of COPS3 mRNA, HBV intracellular pre-genomic RNA and covalently closed circular DNA (cccDNA) in HBV infected PHH cells in vitro resulting from LNA gapmer treatment. See Examples 1 and 2. The data presented in the Specification does not rise to the level of prevention. Regarding “preventing” disorder/disease, it is noted that “preventing” encompasses complete (i.e., 100%) and permanent prevention. One of skill in the art would recognize the complete prevention of any disease in a subject suffering from or susceptible to the disease would be very difficult and there would be a low level of expectation of success (i.e., highly unpredictable).
The specification does not provide any working example demonstrating prevention of any disease in a subject. Therefore, given the lack of knowledge present in the prior art and the lack of guidance provided in the specification with respect to preventing a disease in a subject suffering from or susceptible to the disease, further experimentation would be required. Considering that the additional experimentation would require de novo experimentation without a guarantee of success, and further considering that any positive results (i.e., successful disease prevention in a subject) would amount to a significant advancement in the state of the art, the additional experimentation required is considered undue.
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004).
Furthermore, in In re Vaeck, 947 F.2d 488,495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991), the Court ruled that a rejection under 35 U.S.C. 112, first paragraph for lack of enablement was appropriate given the relatively incomplete understanding in the biotechnological field involved, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims. Such is the case here where there is a relatively incomplete understanding in the biotechnological field involved, as described above, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims.
Without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention. Therefore, it is appropriate to reject the claims under 35 USC 112(a) for not being enabled.
Thus, in view of the breadth of the claims, the lack of guidance, and the lack of working examples, the instant specification is not found to be enabling for the prevention of a disease in a subject. It would require undue experimentation and making a substantial inventive contribution for the skilled artisan to discover how to make and/or use the claimed invention in its full scope.
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Claims 1, 2, 4-7 and 9 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 following quotation from section 2163 of the Manual of Patent Examination Procedure is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirement for a generic claim covering several distinct inventions:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice..., reduction to drawings..., or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus... See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the disclosure must provide written support for the entire scope of the genus. Support for a genus is generally found where the Applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed and that applicant was in possession of the claimed genus.
The claims are drawn to a method of treating or preventing a Hepatitis B virus (HBV) infection in a subject in need thereof, the method comprising administering to the subject a therapeutically or prophylactically effective amount of a COPS3 (COP9 Signalosome Subunit 3) inhibitor. The present Specification discloses:
In some embodiments of the present invention, the inhibitor is an antibody, antibody fragment or a small molecule compound; and
A COPS3 Inhibitor is a nucleic acid molecule of 12-60 nucleotides in length comprising or consisting of a contiguous nucleotide sequence of at least 12 nucleotides in length which is at least 90% complementary to a mammalian COPS3 target nucleic acid
The prior art does not teach a method of treating or preventing a Hepatitis B virus (HBV) infection in a subject in need thereof, the method comprising administering to the subject a therapeutically or prophylactically effective amount of a COPS3 (COP9 Signalosome Subunit 3) inhibitor. The examples of the present application show the reduction of COPS3 mRNA, HBV intracellular DNA and cccDNA in HBV infected primary human hepatocytes (PHH) cells in culture resulting from siRNA treatment with SEQ ID NOs: 10-13. See Table 6A and Example 1. The examples of the present application also show reduction of COPS3 mRNA, HBV intracellular pre-genomic RNA and covalently closed circular DNA (cccDNA) in HBV infected PHH cells in vitro resulting from LNA gapmer treatment with SEQ ID NOs: 23-25. See Table 7 and Example 2. The Specification only provides working examples for SEQ ID NOs. 10-13 and 23-25.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP § 2163. The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a “sufficient number” of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
The instant invention discloses only SEQ ID NOs. 10-13 and 23-25 that function to treat HBV in a subject as claimed. See In re Gostelli 872, F.2d at 1012, 10 USPQ2d at 1618, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus.
The entire genus of COPS3 inhibitor that functions to treat or prevent a HBV infection in a subject in need thereof, does not exist in the instant application. That is, adequate written description support does not exist to practice the full scope of the invention claimed. The Specification nor the art discloses neither a representative number of species compounds nor any structure/function correlation that would enable one of skill to immediately envision the genus of inhibitor of COPS3 that functions to treat or prevent a HBV infection in a subject in need thereof required to practice the full scope of the invention.
As stated above, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic claim. Given the breadth of the claims, the Specification lacks sufficient variety of species to reflect the variance in the genus.
In conclusion, the Specification and the prior art as filed does not provide sufficient descriptive support for the myriad of inhibitor of COPS3 that functions to treat or prevent a HBV infection in a subject in need thereof embraced by the claims. For the reasons discussed above, the 35 USC § 112 rejection for written description is applicable.
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.
Claim Rejections - 35 USC § 102
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.
Claim 27 is rejected under 35 USC § 102 (a)(1) as being anticipated by Yan et al. (Cancer Gene Therapy, 2011 Vol. 18:450-456) (submitted and made of record on the IDS filed June 21, 2022).
The claim is drawn to an in vivo or in vitro method for inhibiting COPS3 expression in a target cell which is expressing COPS3, said method comprising administering a nucleic acid molecule of 12 to 30 nucleotides in length comprising a contiguous nucleotide sequence of at least 12 nucleotides which is 90% complementary to a mammalian COPS3 target sequence, wherein the nucleic acid molecule is capable of inhibiting the expression of COPS3 mRNA in an effective amount to said cell.
Yan et al. demonstrate that siRNA mediated COPS3 gene silencing reduced proliferation and migration of osteogenic sarcoma cell in culture (in vitro) and may be relevant for metastasis.
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Claim 27 is rejected under 35 USC § 102 (a)(1) as being anticipated by Ba et al. (BMC Pharmacology and Toxicology, 2017 Vol. 18, pages 1-14) (submitted and made of record on the IDS filed June 21, 2022).
The claim is as described above.
Ba et al. describe the use of shRNAs for down-regulation of COPS3 in immortalized mouse myoblast cell line, C2C12 cells (in vitro).
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Claim 27 is rejected under 35 USC § 102 (a)(1) as being anticipated by Yoneda-Kato et al. (The EMBO Journal, 2005 Vol. 24:1739-1749) (submitted and made of record on the IDS filed June 21, 2022).
The claim is as described above.
Yoneda-Kato et al. show the reduction in the level of COPS3 protein with siRNA abrogated myeloid leukemia factor (MLF1)-induced G1 arrest and impaired the activation of p53 by genotoxic stress in cultured cells (in vitro).
Claims Free of the Prior Art
Claims drawn to a method of treating a Hepatitis B virus (HBV) infection in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a COPS3 (COP9 Signalosome Subunit 3) inhibitor, wherein the inhibitor is selected from the group consisting of SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 23, SEQ ID NO: 24 and SEQ ID NO: 25 are free of the prior art. Also, claims drawn to an in vivo or in vitro method for inhibiting COPS3 expression in a target cell which is expressing COPS3, said method comprising administering an effective amount of a COPS3 (COP9 Signalosome Subunit 3) inhibitor, wherein the inhibitor is selected from the group consisting of SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 23, SEQ ID NO: 24 and SEQ ID NO: 25 are free of the prior art.
Conclusion
No claims are allowable at this time.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635