DETAILED ACTION
Claims 1-18 are pending in the instant application and under examination.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, 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.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Specifically, paragraphs 83-85, 92, and 97 in the specification contain sequences identified by SEQ ID No. but no sequence listing has been filed in this application.
Specification
The use of the term BLACK HOLE QUENCHER-2 (paragraph 89), FACSMELODY (paragraph 100) and various proprietary dye names (paragraph 55), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 1-18 are 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 a method for detecting biological threats, does not reasonably provide enablement for a method for detecting chemical, radiological or nuclear threats. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The instant claims refer to a sensor that uses labeled polynucleic acids as “specific binding ligands for chemical, biological, and/or radiological/nuclear (CBRN) threats.” When the polynucleic acid binds its target, it produces an optically detectable signal that indicates binding of the CBRN threats. The broadest reasonable interpretation of the claims is that the polynucleic acids act as specific sensors for particular agents of interest. As of the effective filing date of the claims, however, the skilled artisan would not have been able to make and use all such polynucleic acids without undue experimentation.
Around the effective filing date, some systems for sensing agents with polynucleic acids were known. For example, Duan (2016, Anal Methods Vol 8, p1390-1395, cited on the IDS filed November 8, 2022) teaches complexes of carbon nanoparticles and fluorescently labeled DNA aptamers that are specific for pathogenic bacteria. (Scheme 1.) Other systems that use polynucleotides, e.g. aptamers, to bind living biological agents were known as well. The art was also aware of a few aptamers that bind to non-living biological agents, for example Bruno’s teaching of anthrax-spore-binding aptamers. (Biosens Bioelectron. 1999, Vol 14(5), p 457-64)
Beyond systems like Duan’s that detect living biological agents, the art of using polynucleotides as specific probes for CBRN threats remained unpredictable as of the claims’ effective filing date. Saito (Microsystems & Nanoengineering. 2018, Vol 4, p 17083, cited on the IDS filed November 8, 2022) teaches field-deployable systems, but they detect chemical-warfare agents through use of an acetylcholinesterase (AChE) biosensor for nerve-gas agents and rapid PCR for pathogenic bacteria. (Figure 1a.) Yue (Coordination Chemistry Reviews. 2016, Vol 311 p 75-84, as cited on the IDS filed November 8, 2002) teaches a gold-nanoparticle system that detects nerve agents fluorescently, but it likewise makes use of a nanoparticle-enzyme complex, not a polynucleotide sensor. Wei (Anal Bioanal Chem. 2009, Vol 393, p 1943-1948) teaches an aptamer-based system for detecting Botulinum toxin, but it is based on steric hindrance, not energy transfer. Bruno (J. Mol. Recognit. 2009, Vol 22, p 197-204, as cited on the IDS filed November 8, 2022) teaches aptamers for the nerve agent soman but discloses that they cross-react with methylphosphonic acid. (Abstract.)
Lee (Journal of Radiation Protection and Research. 2023, Vol 48(1), p 44-51), writing after the claims’ effective filing date, identifies a single cobalt-specific aptamer, biotinylated LoFA-C1, evolved by SELEX technology. (Page 47, column 2.) Lee teaches, however, that the LoFA-C1 aptamer recognizes all forms of cobalt, including both cobalt-59 (non-radioactive) and cobalt-60 (radioactive). Lee is therefore evidence that even after the claims’ effective filing date, the skilled artisan would not have been able to generate a polynucleic acid specific for radioactive cobalt-60 that does not also bind non-radioactive cobalt-59.
Applicants provide a single relevant working example that detects an unidentified agent with a first DNA aptamer (paragraphs 82-83) and the sarin metabolite methylphosphonic acid with a second one (paragraphs 84-85). This is insufficient to provide the skilled artisan with guidance that would permit him or her to practice the invention without undue experimentation.
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(s) 1, 2, 5, 8-16 and 18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Duan (2016, Anal Methods Vol 8, p1390-1395, cited on the IDS filed November 8, 2022).
Duan teaches a system for simultaneous detection of three different pathogenic bacteria based on fluorescence resonance energy transfer (FRET). Duan teaches that all three pathogenic bacteria cause foodborne illnesses, so they are reasonably interpreted as “biological threats.” (Page 1390, column 1.) In Duan’s system, aptamers specific for the three bacteria connect multicolor dyes to a single carbon nanoparticle (CNP). In this state, the dyes quench each other, so there is no fluorescence. Once the system encounters one or more bacteria that bind the aptamers, however, the aptamer-dye complexes are dislodged from the CNP and fluoresce. See Scheme 1 at page 1392:
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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) 1-16 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Duan (2016, Anal Methods Vol 8, p1390-1395, cited on the IDS filed November 8, 2022) in view of Xing (2018, Analytica Chimica Acta Vol 1042, p 71-78, cited on the IDS filed November 8, 2022).
The teachings of Duan have been described above. Duan does not teach a quantum dot nanoparticle comprising a noble metal in the detection system. These deficiencies are made up for in the teachings of Xing.
Xing teaches an enhanced FRET biosensing system for the detection of HER2 protein. Xing teaches using quantum dots comprising MnCuInS/ZnS encapsulated in bovine serum albumin (page 73).
It would have been prima facie obvious before the effective filing date of the claimed invention for a person having ordinary skill in the art to have used the quantum dots of Xing in the sensor of Duan to detect biological threats because Xing teaches MnCuInS/ZnS quantum dots enable long term aqueous stability and significant enhanced fluorescence activity (page 72 2nd column). Additionally, Xing teaches that the MnCuInS/ZnS quantum dots had lower toxicity.
Thus, the use of Xing’s quantum dots in the sensor of Duan would have been a simple substitution of known FRET detection components to yield predictable results.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANNE M. GUSSOW whose telephone number is (571)272-6047. The examiner can normally be reached Monday to Friday 7am to 4pm, alternate Fridays off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Yvonne Eyler can be reached at 571-272-1200. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683