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 .
Drawings
The drawings are objected to because:
Figures 27, 29 have an “a” in the corner. The reason for the “a” in unclear. Because there are no other panels for these figures.
Figure 28 has panels b and c, but no panel a.
Figures 31 and 39 and 52 have panel c but no panels a or b.
Figure 46 has panels f and g, but no panels a-e.
Figure 53 has panel d yet no panels a-c.
The reasons for this random panel lettering is unclear.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
There is no brief description for Figures 27a and 29a.
There is no brief description for Figure 28 panels b and c.
There is no brief description for Figures 31 and 39 and 52 panel c of each.
There is no brief description for Figure 46 panels f and g.
There is no brief description for Figure 53 panel d.
Appropriate correction is required.
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.
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 4 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.
In claim 4 it is not clear why two different lipids have the same abbreviation. Dimethyldioctadecyl- ammoniumbromide and dimethyldioctadecylammonium are both labeled at DDAB.
Claim 10 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating cancer using the claimed lipid nanoparticle, does not reasonably provide enablement for preventing cancer using the claimed nanoparticle. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or the invention commensurate in scope with these claims.
Applicant claims and discloses the prevention and treatment of cancer. Applicant has provided sufficient evidence to enable treatment of cancer.
Regarding cancer prevention, the skilled artisan recognized that before any method of preventing a particular cancer could be practiced with any level of predictability, some method of identifying subjects predisposed to the particular cancer must be available. While the art has advanced in recent years, it is still highly unpredictable not only which individuals will develop a particular cancer, but also when a “preventative” therapy will be helpful.
Breast cancer illustrates the difficulties associated with detecting and preventing cancer. The skilled artisan generally recognized symptoms of breast cancer to include changes in the breast such as the presence of a lump, nipple discharge, or other changes in the shape or texture of the breast. However, such symptoms are non-specific and have multiple other potential causes. Even detection of a breast mass by mammography is only an early step in the diagnosis of breast cancer. As noted in a 2009 article in the Annals of Internal Medicine and in the 2009 ESMO Clinical Recommendations, following an abnormal mammographic finding or a concerning finding on physical exam, additional imaging and biopsy are required for a diagnosis (cancer vs. benign lesion) and staging is required to determine appropriate treatment. Kataja et al., Ann Oncol 2009; 20(sup 4): iv10-14 (PTO-892); Nelson et al., Ann. Intern Med. 2009; 151:727-737 (PTO-892) - see especially paragraph bridging pages 727-28. Further, even in individuals predisposed to breast cancer by virtue of mutations in BRCA1 or BRCA2, primary preventive treatment with tamoxifen did not show any benefit. Balmana et al. Ann Oncol 2009; 20(supp 4):iv19-20 (PTO-892) – see “risk reduction: non-surgical preventive options" on p. iv19.
Therefore, in view of the state of the art, it is the Examiner’s position that one of skill in the art would undergo undue experimentation to use the lipid nanoparticle for cancer prevention.
Claim 8 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 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.
Claim 8 recites the terminology “STING-active oligonucleotide”. In paragraphs 26-27 of the specification, applicant states that this is a “nucleic acid molecule that bind the STING function to STING”. Applicant has provided no examples of “STING-active oligonucleotides” not does the state of the art provide any guidance as to what is encompassed by this terminology. Therefore, it is the Examiner’s position that “STING-active oligonucleotide” is merely described by its function—i.e. binding STING function.
To satisfy the written description requirement, the 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. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04. 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 a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of genus must be capable of doing, not of the substance and structure of the members.
For a claim drawn to a genus, the written description requirement may be satisfied through sufficient description of a representative number of species by actual reduction to practice 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. 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 (see Official Gazette 1241 OG 174, January 30, 2001).
In the instant case, the claims recite a genus of “STING-active oligonucleotides” which are defined solely in terms of the desired function. Any of a plethora of nucleic acid sequences can have the desired function are encompassed by the claims. The specification describes no such nucleic acid sequences.
In summary, the specification fails to describe at least a substantial number of “STING-active oligonucleotide” claimed and furthermore fails to describe a representative number of oligonucleotides encompassed by the claims. Moreover, the specification does not describe a correlation between any particular identifying (i.e., substantial) structural feature that describes the presupposed representative species and is shared by at least most of the other members of the genus, and any one particular identifying, shared, functional feature that may be attributed to the presence of the structural feature. In an unpredictable art, as here, the disclosure of only one or a few closely related species does not provide the skilled artisan with a representative number of species sufficient to show applicants were in possession of the claimed genus. For these reasons, the skilled artisan would not recognize that applicants were in possession of the invention as broadly claimed at the time the application was filed.
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.
Claim(s) 1-5 and 7-10 is/are rejected under 35 U.S.C. 102a1 as being anticipated by Sahin et al WO 2013/143555 (IDS of 5/2/22).
This reference discloses lipid nanoparticles comprising (1) tumor antigens (including negatively charged RNAs (reads on anion drug), (2) cationic lipids, such as DOTMA, DDAB, DOTAP, DOPSA and DODPA, which is applicant’s DODMA, and cholesterol analogs and derivatives thereof, (3) phospholipids comprising phospholipids having 14-22 aliphatic carbons and (4) adjuvant (summary, pages 15-18, 33-38, page 38, first full paragraph and entire reference). The lipid nanoparticles are used in pharmaceutical compositions for the treatment and prevention of cancer (Page 10, second paragraph and page 11, second paragraph). The adjuvants include CpG oligonucleotides (page 53-54).
Claim Rejections - 35 USC § 103
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(s) 1-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sahin et al WO 2013/143555 (IDS of 5/2/22) in view of Lee et al Theranostics vol. 6 p. 192 (2016 (IDS of 5/2/22), Sahin et al WO 2016/155809(IDS of 5/2/22) and Dravid et al WO 2018/218052 (PTO-892).
Sahin et al ‘555 has been discussed above.
The only difference between the reference and the instant set of claims is the cationic lipid being 3B-[N- (N',N'-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol), GL67, DAP and O-alkyl phosphatidylcholines derivatives and the cholesterol derivative being monoarginine-cholesterol (MA-Chol), .
Lee et al discloses monoarginine-cholesterol (MA-Chol) and its use in lipid nanoparticles in combination with helper lipids and siRNA (abstract and entire reference).
Sahin et al ‘809 discloses lipid nanoparticle formulations comprising cationic lipid and a therapeutically effective compound (summary and entire reference). Page 15 of the reference discloses a variety of cationic lipids used in the formulations and these include DOTMA, DDAB and DC Chol.
Dravid et al discloses nanoparticle lipid compositions comprising DODAB, DOTMA, DAP, DDAB, DOTAP, GL67 and EPC’s (which read on applicant’s O-alkyl phosphatidylcholines derivatives) and the use these nanoparticles in treatment of cancers (summary and entire reference).
Since Sahin et al ‘555 discloses lipid nanoparticles comprising (1) tumor antigens (including negatively charged RNAs (reads on anion drug), (2) cationic lipids, such as DOTMA, DDAB, DOTAP, DOPSA AND DODPA, which is applicant’s DODMA and cholesterol analogs and derivatives thereof, (3) phospholipids comprising phospholipids having 14-22 aliphatic carbons and (4) adjuvant and since Lee et al discloses that monoarginine-cholesterol (MA-Chol) can be used in similar lipid nanoparticle compositions, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use monoarginine-cholesterol (MA-Chol) in the lipid nanoparticles of Sahin et al ‘555 with the expected benefit of making lipid nanoparticles. Since Sahin et al ‘809 discloses lipid nanoparticle formulations comprising cationic lipid DOTMA, DDAB and DC Chol, it also would have been obvious to a skilled artisan to use DC Chol in the lipid nanoparticles of Sahin et al ‘555 with the expected benefit of making lipid nanoparticles. Additionally, since Dravid et al discloses nanoparticle lipid compositions comprising DODAB, DOTMA, DAP, DDAB, DOTAP, GL67 and EPC’s, it also would have been obvious to use any of those lipids as the lipids in Sahin et al ‘555.
Claim(s) 11-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sahin et al WO 2013/143555 (IDS of 5/2/22) in view of Zhao et al J. Immunol. Res. Article ID 3673295 (9/20418) (IDS of 5/2/22) and Pravda US 7312243(PTO-892).
Sahin et al ‘555 has been discussed above.
The only difference between the reference and the claimed invention is the formation of a kit and the combination of the nanoparticles with anti-PD-L1 and anti-PD-1 antibodies.
Zhao et al disclose the combination therapy of nanoparticles and checkpoint blockade antibodies, such as anti-PD-1 and anti-PD-L1 antibodies (page 2-9).
Pravda et al discloses the formation of kits for the ease of administration to a person (col. 7, lines 10-15 and col. 12, line 65-col. 13, line 25.
Since Zhao et al disclose the combination therapy of nanoparticles and checkpoint blockade antibodies, such as anti-PD-1 and anti-PD-L1 antibodies, and since Sahin et al discloses lipid nanoparticles for treatment of cancers, it would have been obvious to use the nanoparticles of Sahin et al in combination with anti-PD-1 and anti-PD-L1 antibodies with the expected benefit of treating cancer. As disclosed by Pravda et al formation of kits for the ease of administration to a person it known in the art. Thus, it would have also been obvious to form a kit using the nanoparticle and the anti-PD-1 and anti-PD-L1 antibodies. With respect to the kit comprising a first and second vaccine composition, this is within the purview of one skilled in the art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHEELA J HUFF whose telephone number is (571)272-0834. The examiner can normally be reached M-Th 6:30am to 4pm Eastern Time.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Sheela J. Huff/ Primary Examiner, Art Unit 1643
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