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 .
Status of the Claims
Claims 25-42 are pending and examined herein.
Priority
This application, filed 01/29/2024, is a 371 of PCT/IL2022/050838, filed 08/02/2022, which claims benefit of PRO 63/228,283, filed 08/02/2021. This benefit is acknowledged and the claims examined herein are treated as having an effective filing date of 08/02/2021.
Information Disclosure Statement
The Information Disclosure Statement filed 01/29/2024 is acknowledged and has been considered.
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 25-34 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 25 recites “detecting” antibodies in a sample and “thereby, obtaining a diagnosis of autoimmune autonomic ganglionopathy”; however, it is unclear how the diagnosis of AAG is “obtained”. In particular, it is unclear how the diagnosis is “obtained” relating to the detection of the antibodies, which is merely the determination of a single concentration in a sample, without any other analysis such as a comparison to a pre-determined threshold. Further, as claimed, the diagnosis of AAG could be “obtained” from any source without the use of the detected level of antibodies, as there is no methodological connection between the detection and diagnosis within the claimed method.
Claims 26-34 are further rejected for being dependent on claim 25.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 29 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. In this case, claim 29 is dependent on claim 25. Claim 25 recites “engineering cells to express (i) α3 subunit…and (ii) at least one chaperon”. Claim 29 recites “wherein said engineering is conducted by means of molecular biology or genetic engineering”; however, any cells that are engineered to express specific proteins or subunits, as claimed in claim 25, would, by necessity, be engineered by means of molecular biology and/or genetic engineering. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 25-34 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon/law of nature without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to§ 101 (see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the claim is "directed to," we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a
fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical
application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an "'inventive concept' sufficient to 'transform"' the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not "well-understood,
routine, conventional" in the field (see MPEP § 2106.0S(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception. See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
Claim 1 recites “A cell-based method for detecting antibodies against α3 subunits of the neuronal nicotinic acetylcholine receptors in a subject, comprising…detecting a reaction between said at least one protein and said antibodies found in said body fluid or tissues, thereby, obtaining a diagnosis of autoimmune autonomic ganglionopathy (AAG) for said patient.”
The natural relationship to which the claims are directed (i.e., the relation between levels of antibodies against α3 subunits of the neuronal nicotinic acetylcholine receptors and AAG) is a law of nature. Similar concepts have been held by the courts to constitute law of nature/natural phenomena, as in the identification of a correlation between the presence of myeloperoxidase in a bodily sample (such as blood or plasma) and cardiovascular disease risk in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017). In Mayo, the Supreme Court found that a claim was directed to a natural law, where the claim required administering a drug and determining the levels of a metabolite following administration, where the level of metabolite was indicative of a need to increase or decrease the dosage of the drug. See Mayo Collaborative Services v. Prometheus Labs., Inc., 566 U.S. 66, 74 (2012).
The instant claims are similar to those in Mayo as they involve a "relation itself [which] exists in principle apart from any human action" (id. at 77), namely the relationship between the naturally occurring levels of antibodies against α3 subunits of the neuronal nicotinic acetylcholine receptors in body fluid and the presence of AAG.
The correlation between anti-α3 antibodies and disease is a judicial exception as it exists in principle apart from any human action; the correlation itself therefore cannot form the basis for eligibility.
Step 2A, Prong 2
The above-discussed steps of “detecting” anti-α3 antibodies and “obtaining” a diagnosis of AAG are insufficient to integrate into a practical application because steps corresponding to a law of nature are insufficient to constitute a practical application. In this case, detecting antibodies and diagnosing represent judicial exceptions and not a practical application thereof.
The claims also recite “engineering cells to express (i) α3 subunit…and (ii) at least one chaperon”, “culturing said cells”, and “exposing said cells to body fluid or tissue from said subject” (Claim 1). Such steps are considered to be insignificant presolution activity, i.e., a mere data gathering step necessary to use the correlation, similar to the fact pattern in In re Grams, 888 F.2d 835 (Fed. Cir. 1989) and Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015) because their purpose is merely to obtain data to use the correlation. Further the step of “detecting a reaction” is recited at a high level of generality and is not tied, for example, to any particular machine or apparatus.
Regarding the dependent claims 26-34, the claims are directed toward limiting the insignificant presolution activity and fail to integrate the judicial exception into a practical application. Claim 26 is directed at broadly limiting the type of antibody that is detected. Claim 27 is directed toward limiting the type of subject that is tested. Claims 28-30 are directed toward limiting the cells that are used for detecting the antibodies. Claims 31 and 32 are directed to limiting the conditions by which the cells are cultured. Claim 33 is directed toward the type of sample used from the subject. Claim 34 broadly limits the type of reaction used for detecting the antibodies. None of the limitations recited at the indicated dependent claims amount to a practical application of the judicial exceptions. In particular, of the claims indicated in the rejection heading, none of the additionally recited limitations amount to an additional element or combination of elements that apply, rely on, or use the judicial exceptions in a manner that impose meaningful limit on the judicial exceptions.
ELIGIBILITY OF STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN “INVENTIVE CONCEPT”
Further, the additional elements of the claims (the active method steps/limitations recited in addition to the judicial exceptions themselves) do not add significantly more to the judicial exception(s); the additional recited claim elements are recited at a high level of generality, and are not, for example, limited to any particular testing technique or platform as claimed.
Nakane et al., “Clinical Features of Autoimmune Autonomic Ganglionopathy and the Detection of Subunit-Specific Autoantibodies to the Ganglionic Acetylcholine Receptor in Japanese Patients” PLoS One (published 03/19/2015, referred to herein as Nakane) supports that the detection of anti-α3 antibodies for the diagnosis of AAG was a known, art accepted method for AAG diagnosis. At the same time, Kuryatov et al., “Chemical Chaperones Exceed the Chaperone Effects of RIC-3 in Promoting Assembly of Functional α7 AchRs” PLoS One (published 04/24/2013, referred to herein as Kuryatov) supports that cell-based assays, with engineered cells to express specific nAChR subunits and chaperones, was a known, art-recognized method for the detection of anti-nAChR subunit-specific antibodies.
The claimed limitations as currently presented fail to recite limitations that add a feature that is more than well-understood, conventional or routine in the field of anti-nAChR subunit-specific antibody detection.
For all of these reasons, the claims fail to include additional elements that are sufficient to either integrate the judicial exception(s) into practical application(s) thereof, or amount to significantly more than the judicial exception(s).
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 40 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nakane et al., “Clinical Features of Autoimmune Autonomic Ganglionopathy and the Detection of Subunit-Specific Autoantibodies to the Ganglionic Acetylcholine Receptor in Japanese Patients” PLoS One (published 03/19/2015, referred to herein as Nakane).
Regarding claim 40, Nakane teaches a cell carrying an expression vector for expressing the α3 subunit of the nicotinic acetylcholine receptor (p. 4, para. 2, lines 4-6).
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 25-34 and 41-42 are rejected under 35 U.S.C. 103 as being unpatentable over Nakane et al., “Clinical Features of Autoimmune Autonomic Ganglionopathy and the Detection of Subunit-Specific Autoantibodies to the Ganglionic Acetylcholine Receptor in Japanese Patients” PLoS One (published 03/19/2015, referred to herein as Nakane) in view of Kuryatov et al., “Chemical Chaperones Exceed the Chaperone Effects of RIC-3 in Promoting Assembly of Functional α7 AchRs” PLoS One (published 04/24/2013, referred to herein as Kuryatov).
Regarding claim 25, Nakane teaches a method for detecting antibodies against α3 subunits of the neuronal nicotinic acetylcholine receptors in a subject (Abstract, lines 5-8) comprising engineering cells to express the α3 or β4 subunits (p. 4, para. 2, lines 1-6), culturing said cells in media for two days (p. 4, para. 2, line 7) which could contain at least one substance. Nakane teaches contacting the subunits with serum from subjects (p. 4, para. 2, lines 8-10) and detecting a reaction between the subunits and antibodies in the serum (p. 4, para. 2, lines 10-16). Nakane teaches detecting the antibodies is used to diagnose a patient with AAG (p. 10, para. 3, lines 5-9).
However, Nakane does not teach a method comprising engineering cells to express the α3 and β4 subunits together.
Nakane does teach that it is possible that a pentamer-specific antibody exists in AAG patient serum (p. 13, para. 3, lines 16-18) which would require the presence of all 5 subunits, including α3 and β4 subunits.
It would have been obvious to one of skill in the art before the effective filing date of the claimed invention to modify the method taught by Nakane by expressing the α3 and β4 subunits, among others, in the cells. Doing so would enable the detection of pentamer-specific antibodies which could be present in AAG patient serum, as taught by Nakane. An artisan would have a reasonable expectation of success in making this change because expression of these subunits is well-known in the art and would be used to form a naturally occurring pentameric complex in cells, which could be used to detect antibodies using the method taught by Nakane.
Regarding claim 26, Nakane teaches detecting IgG antibodies (Abstract, lines 5-6).
Regarding claim 27, Nakane teaches detecting the antibodies in a subject who suffers from AAG, which is a neurological disorder (Abstract, lines 16-17).
Regarding claim 29, Nakane teaches that the cells are engineered using molecular biology and genetic engineering (p. 4, para. 2, lines 1-6).
Regarding claim 30, Nakane teaches using human cells (p. 4, para. 2, lines 4-6).
Regarding claim 33, Nakane teaches using patient serum (p. 4, para. 2, lines 8-10).
Regarding claim 34, Nakane teaches detecting the antibodies using luminescence (p. 4, para. 2, line 1).
However, Nakane does not teach a cell-based method comprising engineering cells to express at least one chaperon and exposing said cells to body fluid (claim 25), wherein the chaperon is RIC-3 or NACHO (claim 28). Nakane does not teach culturing the cells with a specific substance configured to affect expression levels of the α3 subunit (claims 31 and 32).
Regarding claims 25, 28, 31-32, and 41-42, Kuryatov teaches a cell-based method for detection nAChR antibodies comprising engineering cells to express nAChR subunits and the chaperon, RIC-3, (p. 2, col. 2, para. 1, lines 6-7) and culturing the cells with nicotine (Figure 3 legend, lines 8-10) to increase assembly of the nAChR complex on the cell surface of fixed cells (p. 9, col. 2, para. 3, lines 6-9).
It would have been obvious to one of skill in the art before the effective filing date of the claimed invention to modify the method taught by Nakane by expressing the RIC-3 chaperon and culturing the cells with nicotine. An artisan would have been motivated to make this change in order to increase expression and assembly of nAChR complexes on the cells, which are the binding targets for the antibodies of interest. An artisan would have had a reasonable expectation of success in making this change because, as taught by Kuryatov, this is a successful strategy for increasing nAChR complex expression and assembly in HEK cells, which are the cells used by Nakane.
Further, it would have been obvious to one of skill in the art before the effective filing date of the claimed invention to modify the method taught by Nakane by detecting complexes on live or fixed cells, as taught by Kuryatov. An artisan would have been motivated to make this change in order to detect antibodies by providing nAChR complexes in their surface-bound confirmation, which is the natural state of the complex. An artisan would have had a reasonable expectation of success because, as taught by Kuryatov, this is a successful method for the detection of anti-nAChR complex antibodies, such as those detected by Nakane.
Claims 35-39 are rejected under 35 U.S.C. 103 as being unpatentable over Nakane in view of Kuryatov as applied to claims 25-34 and 41-42 above, and further in view of US 4,208,479 (published 06/17/1980, referred to herein as Zuk).
The teachings of Nakane in view of Kuryatov, as applied to claims 25-34 and 41-42 above, is incorporated herein.
Regarding claim 35, Kuryatov teaches growing cells in medium and washing with buffer (p. 4, col. 2, para. 2, lines 1-5).
Regarding claim 36, Nakane teaches using human cells (p. 4, para. 2, lines 4-6).
Regarding claim 37, Nakane teaches engineering cells to express the α3 or β4 subunits (p. 4, para. 2, lines 1-6)
Regarding claim 38, Kuryatov culturing the cells with nicotine (Figure 3 legend, lines 8-10)
Regarding claim 39, Kuryatov teaches using cells fixed with formalin (p. 4, col. 2, para. 2, lines 3-5).
However, Nakane in view of Kuryatov does not specifically teach the components of the assay in a kit.
However, Zuk teaches that in performing assays, it is convenient and to combine the necessary reagents together in a kit (column 22, lines 20-68 in particular). Zuk further teaches that this may improve assay accuracy.
Therefore, it would have been obvious to one of ordinary skill in the art to provide the components of the assay taught by Nakane in view of Kuryatov together in kit form for convenience and accuracy as taught by Zuk.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTOPHER EVANS whose telephone number is (571)272-4897. The examiner can normally be reached Mon - Fri 8:30am to 4:30pm EST.
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, Bao-Thuy Nguyen can be reached at (517) 272-0824. 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.
/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 June 24, 2026
Prosecution Insights