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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is a 371 of PCT/US2020/043784 filed July 27, 2020, which claims the benefit of US Provisional Application No. 62/878,867 filed July 26, 2019. All claims have been given an effective filing date of July 26, 2019.
Election/Restriction
Applicant's election without traverse of Group I (Claims 1-11 and 20) in the reply filed on February 6, 2026 is acknowledged.
Claims 12-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 6, 2026.
Claim Status
Claim listing filed on July 5, 2022 is pending. Claims 21-25 are canceled. Claims 3-6, 14, and 16 are amended. Claims 12-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions or species. Claims 1-11 and 20 are examined upon their merits.
Information Disclosure Statement
The information disclosure statement filed on 04/06/2022 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities:
Paragraph [0004] is missing a period at the end of the last sentence.
Examiner believes there is a typographical error in the last line of paragraph [0110] that recites “nor were they on any blood.”
In paragraph [0164], “A novel quantitative” in the first sentence is incorrectly apart of the title instead of being properly recited after the paragraph number.
Appropriate correction is required. Applicant is urged to carefully review the specification for additional informalities.
Claim Objections
Claims 3, 5, and 10-11 are objected to because of the following informalities:
Claim 3 requires a comma after the preamble to recite “The method of claim 1,”
Claim 5 recites “in a cell suspension peripheral blood mononuclear cells” wherein “in a cell suspension of peripheral blood monocular cells” is correct.
Claim 10 recites “The method according to claims 9,” and in order to match the formatting of the other claims, “The method, according to Claim 9,” is correct which adds a comma after “method”; capitalizes “Claim”; and makes “Claim” singular.
Claim 11 recites “MAO B inhibitor” wherein “MAO-B inhibitor” with a hyphen is used in the art.
Appropriate correction is required.
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.
Claims 1 and 3-11 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 1 recites “at least one mediator of dopamine transmission.” Claims 3-11 are dependent on Claim 1 and do not further define the claimed mediator. This phrase is considered functional language because the feature (the mediator) is defined by what it does (mediates dopamine transmission) rather than by what it is (MPEP § 2173.05(g)). To determine if functional language is ambiguous, the following factors are considered: (1) whether there is a clear cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim. These factors are examples of points to be considered when determining whether language is ambiguous and are not intended to be all inclusive or limiting (MPEP § 2173.05(g)). The specification does not define “mediator of dopamine transmission.” In the art, multiple agents are involved in dopamine transmission directly or indirectly such as vesicular monoamine transporter 2 (VMAT2), various dopamine receptors (D1-D5), syntaxin 1A, etc. The structural metes and bounds of what is considered a mediator of dopamine transmission is unclear. For example, would psychostimulants such as methylphenidate be considered a mediator of dopamine transmission since it inhibits dopamine transporter and enhances dopamine presence? One of ordinary skill would not understand that clear structural boundaries of what is encompassed by “mediator of dopamine transmission,” and Claims 1 and 3-11 are rejected for indefiniteness.
Claim 4 encompasses the trademarked media CryoStor10® as an essential claimed element. Applicant should note that a trademark or tradename does not denote a particular and fixed element. For example, the tradename “Coca-Cola” has been used on different formulations over the years. MPEP 2173.05(u) states: “If the trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of the 35 U.S.C. 112(b). Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982)….The claim scope is uncertain since the trademark or trade name cannot be used properly to describe any particular material or product. In fact, the value of a trademark would be lost to the extent that it became the generic name of a product, rather than used as an identification of a source or origin of a product. Thus, the use of a trademark or trade name in a claim to describe a material or product would not only render a claim indefinite, but would also constitute an improper use of the trademark or trade name.” Claim 4 is rejected for indefiniteness by claiming a trademarked product. For the purpose of compact prosecution, CryoStor10® is interpreted as any cryopreservation media known in the art prior to the time of filing.
Claim 4 is further indefinite because it is unclear at what point in the method the cell suspension is cryopreserved. Is the cell suspension cryopreserved before staining, after staining, before performing flow cytometry, or after performing flow cytometry? Claim 1 is directed to a method comprising chronological steps, and it is unclear at what point in the method the cell suspension is cryopreserved as recited in Claim 4.
Claim 6 recites the limitation "the healthy subject" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 6 recites the limitation "the average level" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claims 7-11 are rejected for their dependence on indefinite Claim 6. For the purpose of compact prosecution, Claim 6 is interpreted as depending from Claim 5 wherein “a healthy subject” is defined. Further, “the average level” is interpreted as “the control level” as defined in Claim 5.
Claim 6 recites “about 12% PBMCs.” The specification recites “the term ‘about’ generally refers to a range of numbers that one of skill in the art would consider equivalent to the recited value (i.e., having the same function or result)” (paragraph [0065]). This definition is indefinite because it would be unclear to one of ordinary skill what constitutes a functional equivalent of “12% PBMCs.” Would 10%, 20%, or 25% PBMCs be considered functionally equivalent? The metes and bounds of “about 12% PBMCs” are indefinite (MPEP § 2173.05(b)III.A).
Claim 6 is indefinite because it recites the abbreviation “PBMCs” without defining the abbreviation in the claims. For the purpose of compact prosecution, “PBMCs” is interpreted as “peripheral blood mononuclear cells.” Appropriate correction is required.
Note, Claim 7 recites “comparing the level with the average level,” and “the level” is interpreted as the level of at least one mediator of dopamine transmission from a first subject as defined in Claim 1. Note, Claim 20 recites “comparing the level of TH in the biosample with a control biosample” and is interpreted as comparing the level of TH in the biosample with a level of TH in a control biosample.
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 and 3-11 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 claims contain 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.
Claim 1 recites a method for detecting at least one mediator of dopamine transmission which comprises a genus of agents that can comprise any structure as long as they affect dopamine transmission directly or indirectly. Claim 7 is directed to diagnosing any type of disease based in part on comparing the level of dopamine transmission mediator with a control level. The claims do not recite if the level of dopamine transmission mediator must be above or below the control level to diagnose the disease. Therefore, the claims broadly encompass detecting a genus of agents and diagnosing a genus of diseases if the agent is above or below a control level.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. In order to provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, or any combination thereof.
In the instant case, the specification teaches the detection of two species of dopamine transmission mediators, tyrosine hydroxylase (TH) and dopamine transporter (DAT) (paragraph [0130]). The levels of both TH and DAT in PBMCs from Parkinson’s disease patients were significantly increased as compared to healthy controls (paragraph [0075] and Fig. 9). Therefore, the specification teaches detecting the level of two species of dopamine transmission mediators to diagnose one disease. These working examples are not sufficient to describe detecting a genus of agents and diagnosing a genus of diseases.
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 AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (MPEP § 2163.05.Ib). There is substantial variation in the genus of claimed mediators and the genus of claimed diseases. In the absence of sufficient recitation of distinguishing identifying characteristics or structure-to-function attributes for the entire genus of dopamine transmission mediators, the specification does not provide adequate written description of the claimed genus. Further, without a representative number of examples diagnosing various diseases based on various levels of dopamine transmission mediators, the specification does not provide adequate written description of the claimed methods. Therefore, in view of the case law directed to an appropriate number of representative species, claims 1 and 3-11 are rejected for insufficient written description.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see page 1115).
Claims 1 and 3-11 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 detecting levels of TH and DAT (Claim 2) and DRD3 to diagnose Parkinson’s disease, does not reasonably provide enablement for detecting a genus of dopamine transmission mediators and diagnosing a genus of diseases.
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.
MPEP § 2164.01(a) states that there are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure
does not satisfy the enablement requirement and whether any necessary experimentation is
“undue”. These factors include, but are not limited to:
A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
The breadth of the claims and nature of the invention:
The nature of the invention is complex, encompassing detecting at least one mediator of dopamine transmission which comprises a genus of agents that can comprise any structure as long as they affect dopamine transmission directly or indirectly (Claim 1). Claim 7 is directed to diagnosing any type of disease based in part on comparing the level of dopamine transmission mediator with a control level. The claims do not recite if the level of dopamine transmission mediator must be above or below the control level to diagnose the disease. Therefore, the claims broadly encompass detecting a genus of agents and diagnosing a genus of diseases if the agent is above or below a control level.
When analyzing the scope of enablement, the claims are analyzed with respect to the teachings of the specification and are to be "given their broadest reasonable interpretation consistent with the specification." See MPEP 2111 [R-5]; Phillips v. AWH Corp., 415 F.3d 1303, 75 USPQ2d 1321 (Fed. Cir. 2005); and In re Hyatt, 211 F.3d 1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000). Applicant always has the opportunity to amend the claims during prosecution, and broad interpretation by the examiner reduces the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550- 51 (CCPA 1969).
The state of the prior art and level of predictability in the art:
The level of predictability in the art depends, most importantly, on whether the claimed invention can be practiced by one of ordinary skill in the art. Elgueta et al. Front Immunol. May 2019 (of record) teaches the detection of dopamine receptor D3 (DRD3) expression in PBMCs from Parkinson’s disease patients (page 3, paragraph 3) and that DRD3 is significantly reduced in Parkinson’s disease patients as compared to healthy controls (Discussion paragraphs 1-2). The art prior to the time of filing teaches the detection of one species of dopamine transmission mediator to diagnose one disease. The state of the art does not provide enablement for detecting any type of dopamine transmission mediator to diagnose Parkinson’s disease or any other type of disease. The art shows a lack of predictability in the claimed method, and there is no support in the Applicant’s disclosure leading one of ordinary skill to overcome the lack of predictability in detecting any type of dopamine transmission mediator to diagnose any type of disease.
Level of skill in the art:
The level of skill would be high encompassing neurology, oncology, virology, molecular biology, protein detection, etc.
Amount of direction provided by inventor and the existence of working examples:
The specification teaches the detection of two species of dopamine transmission mediators, tyrosine hydroxylase (TH) and dopamine transporter (DAT) (paragraph [0130]). The levels of both TH and DAT in PBMCs from Parkinson’s disease patients were significantly increased as compared to healthy controls (paragraph [0075] and Fig. 9). Therefore, the specification teaches detecting the level of two species of dopamine transmission mediators to diagnose one disease. These working examples are not sufficient to describe detecting a genus of agents and diagnosing a genus of diseases. A person having ordinary skill in the art would have to make a substantial inventive contribution in order to detect any type of dopamine transport mediator and diagnose any type of disease, since there is no guidance within the disclosure as filed pertaining to these embodiments.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
In light of the unpredictability surrounding the claimed subject matter, the breadth of the claimed invention’s intended use, and the lack of adequate guidance, one wishing to practice the presently claimed invention would be unable to do so without engaging in an unknown quantity of experimentation. Specifically, one of ordinary skill would be required to develop protocols to detect a representative number of dopamine transport mediators and measure the levels in a representative number of diseases as compared to healthy controls. This level of experimentation in order to practice the invention commensurate with the scope of the claims is considered undue. The instant specification does not enable the method of detecting any type of dopamine transmission mediator and diagnosing any type of disease (Claims 1 and 3-11).
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 5-10 and 20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to an abstract idea and/or law of nature without significantly more.
Claim 5 is directed to the abstract idea of “comparing” in comparing the level of at least one mediator of dopamine transmission with a control level. Claim 6 is interpreted as dependent on Claim 5 (see 112(b) section above). Claims 7-9 are directed to the abstract ideas of “diagnosing” and “comparing” in diagnosing a disease based at least in part on comparing the level with the control level. Claims 7-9 are also directed to a law of nature by describing a correlation or relationship between the level of dopamine transmission mediator in a subject’s blood and the presence of a disease in the subject, specifically Parkinson’s disease. This type of correlation is a consequence of nature. Claim 10 recites administering a Parkinson’s therapy to the diagnosed subject, but the treatment step is claimed at a high level of generality without listing any specific drug types. Claim 20 is directed to the abstract idea of “comparing” in comparing the level of TH in a biosample with a control biosample.
These judicial exceptions are not integrated into a practical application because the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. Nothing beyond use of routine and conventional methods are encompassed by the claims in addition to the judicial exceptions. Therefore, claims 5-10 and 20 do not include additional elements that are sufficient to amount to significantly more than the judicial exceptions.
The rationale for this determination is explained below:
The unpatentability of laws of nature/natural phenomenon was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 101 USPQ2d 1961 (March 20, 2012), and Association for Molecular Pathology v. Myriad Genetics, Inc. 106 USPQ2d 1972 (2013).
Accordingly, the issues are:
a) The claims are directed to a method (Step 1: YES). The claims are directed to a method of observing a natural law/natural phenomenon (i.e., the correlation of dopamine transmission mediator levels and the presence of a disease) (MPEP § 2106.04(b).I), wherein the method uses the abstract/mental concepts of “comparing” and “diagnosing” (MPEP § 2106.04(a)(2).III.A). Therefore, the claims do not overcome Prong One (Step 2A- Prong One: YES).
b) The claims fail to recite a practical application of additional elements that integrate the judicial exception into a practical application. Besides the judicial exceptions, the claims recite additional steps of obtaining biosamples and detecting the level of a dopamine transmission mediator by any means known in the art (Claim 20) or flow cytometry (Claims 5-10). Obtaining a blood sample in order to perform tests is well-understood, routine, and conventional activity for those in the field of diagnostics. Similarly, detecting a level of a dopamine transmission mediator when recited at this high level of generality does not impart a meaningful limitation or unconventional procedure that distinguishes it from well-understood, routine, and conventional techniques of protein detection in the art prior to filing. See USPTO Subject Matter Eligibility Examples: Life Sciences, May 2016, Example 29.
One way to integrate a judicial exception into a practical application is to affect a particular treatment for a disease. The treatment must be “particular” and generically claiming “administering a suitable medication to a patient” is not sufficient for a practical application (MPEP § 2106.04(d)(2)). Claim 10 recites a treatment that is not particular by reciting “administering a Parkinson’s therapy.” Claimed at this high level of generality, treating a patient diagnosed with Parkinson’s disease with a Parkinson’s therapy merely instructs to “apply” the judicial exception in a generic way (Step 2A- Prong Two: NO). Note, Claim 11 does integrate the judicial exception into a practical application by providing a particular treatment comprising a specific drug type (levodopa, COMT inhibitor, amantadine, etc.).
c) Nothing significantly more than the judicial exceptions is recited within the claims. The courts have defined that simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to a judicial exception is not “significantly more” (MPEP § 2106.05.I.A). The courts have recognized that (1) determining the level of a biomarker in blood by any means and (2) detecting DNA or enzymes in a sample are routine activities in the life sciences when claimed at a high level of generality (MPEP § 2106.05(d).II; emphasis added) (Step 2B: NO).
In Mayo Collaborative Services it was held that:
"Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work." Gottschalk v. Benson, 409 U. S. 63, 67 (1972). And monopolization of those tools through the grant of a patent might tend to impede innovation more than it would tend to promote it. [emphasis added].
The Court has made clear that to transform an unpatentable law of nature into a patent-eligible application of such a law, one must do more than simply observe and restate a law of nature while adding the words "apply it." As set forth in the decision,
"[i]f a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself," further, "[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately. [emphasis added]"
The discovery of a naturally-occurring correlation between the level of dopamine transmission mediator and presence of a disease is merely the observation of a law of nature. Accordingly, the current claims simply rely on the recognition of a natural relationship between a patient’s protein levels and disease phenotype.
In summary, merely “comparing” the level of a dopamine transmission mediator and “diagnosing” a disease encompasses both abstract ideas and laws of nature. Applying the judicial exceptions to generically administer Parkinson’s therapy to patients diagnosed with Parkinson’s disease does not result in significantly more than the judicial exceptions.
For these reasons, claims 5-10 and 20 are rejected under section 101 as being directed to non-statutory subject matter.
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.
Claims 1 and 5-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Elgueta et al. Front Immunol. May 2019 (of record).
In regard to Claim 1, Elgueta teaches that human peripheral blood mononuclear cells (PBMCs) were obtained from Parkinson’s disease patients and analyzed for dopamine receptor D3 (DRD3) expression by immunostaining with fluorescent markers and passing the cells through a flow cytometer (page 3, paragraph 3). DRD3 reads on at least one mediator of dopamine transmission.
In regard to Claims 5-6, Elgueta teaches that the level of DRD3 was also detected in PBMCs from age-matched healthy controls (HC) (page 3, paragraphs 2-3). The DRD3 expression levels were compared between the healthy controls and the Parkinson’s disease patients (page 7, last paragraph). The DRD3 expression levels in HC ranged from 2-12% PBMCs depending on immune cell type (Fig. 1A) which reads on “about 12% PBMCs” in Claim 6.
In regard to Claims 7-9, Elgueta teaches that DRD3 expression was significantly reduced in Parkinson’s disease patients as compared to healthy controls, and DRD3 expression could represent a useful marker for diagnostic analysis (Discussion paragraphs 1-2).
Therefore, Claims 1 and 5-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Elgueta.
Claim 20 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Caronti et al. NeuroReport 10, 2907-2910 (1999) as evidenced by StemCell Technologies 2026.
In regard to Claim 20, Caronti teaches measuring tyrosine hydroxylase (TH) in peripheral blood lymphocytes (PBL) obtained from Parkinson’s disease patients and healthy controls (introduction paragraphs 1-3). The level of TH was detected by immunohistochemistry utilizing biotinylation and diaminobenzidine staining and compared between Parkinson’s disease patients and the healthy controls (page 2908 paragraph 2 and page 2909 paragraph 1). Note, Caronti teaches that the PBL samples were prepared by Ficoll gradient centrifugation of blood samples (page 2908 paragraph 1). StemCell Technologies 2026 teaches that PBMCs comprise both lymphocytes and monocytes, and PBMCs are isolated from blood via Ficoll gradient centrifugation (‘Composition of Human Peripheral Blood Mononuclear Cells’). Therefore, wherein Caronti references “PBL,” the cell samples prepared by Ficoll gradient centrifugation were more generally PBMCs that comprise both lymphocytes and monocytes.
Therefore, Claim 20 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Caronti as evidenced by StemCell Technologies.
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.
Claims 1-2, 5, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Caronti et al. NeuroReport 10, 2907-2910 (1999) as evidenced by StemCell Technologies 2026, and in view of Wolf et al. J Neurochem. 1989.
The teachings of Caronti as they apply to Claim 20 are outlined above and comprise a method of detecting TH in PBMCs in Parkinson’s disease patients and healthy controls and comparing the TH levels.
Caronti fails to teach wherein the TH is stained with a fluorescent marker and the cells are passed through a flow cytometer (Claim 1).
However, Wolf teaches a method of detecting TH by binding primary anti-TH antibodies and secondary fluorescent antibodies prior to performing flow cytometric analysis to quantify the level of TH (page 880 paragraphs 4-5). Wolf teaches that flow cytometry is a high-throughput analysis wherein 20,000 events were typically collected for analysis (page 880 paragraphs 5).
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to modify the method of detecting TH in PBMCs taught by Caronti to specifically use anti-TH fluorescent markers and flow cytometry as taught by Wolf. Caronti teaches that about 100 cells were measured for each patient sample (page 2908 paragraph 1), and Wolf teaches that flow cytometry is high-throughput and can analyze 20,000 events per sample. It would have been obvious to one of ordinary skill that the high-throughput method of flow cytometry is preferable to evaluate more cells in a sample to yield more precise results. Therefore, there is motivation to apply the known anti-TH flow cytometry method of Wolf to the Parkinson’s disease PBMCs of Caronti to quantify TH levels in samples with high precision.
Claims 1 and 3-9 are rejected under 35 U.S.C. 103 as being unpatentable over Elgueta et al. Front Immunol. May 2019 (of record) in view of Barcelo et al. Curr Protoc Cytom 2018 (of record in IDS).
The teachings of Elgueta as they apply to Claims 1 and 5-9 are outlined above. Elgueta fails to teach wherein the cell suspension is cryopreserved prior to detecting the level of the at least one mediator of dopamine transmission (Claim 3) and wherein the cell suspension is cryopreserved with known media (Claim 4).
However, Barcelo teaches that the collection and cryopreservation of viable cells from blood samples is becoming increasingly common in large patient cohorts, and these cells are a valuable resource for immunophenotyping and functional studies (abstract). Barcelo teaches protocols for the cryopreservation of PBMCs, thawing, and immunophenotyping via flow cytometry (abstract and introduction paragraph 2). The cryopreservation media comprises 20% FCS in supplemented RPMI with HEPES and 20% DMSO (page 5 steps 15-16).
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to modify the method of detecting DRD3 expression in PBMCs by flow cytometry as taught by Elgueta to include cryopreservation of the PBMCs prior to flow cytometry as taught by Barcelo. Barcelo teaches that cryopreservation of PBMCs prior to flow cytometry is a standard protocol known in the art prior to filing, and one of ordinary skill would be motivated to cryopreserve samples to provide long-term storage prior to analysis especially in samples obtained from large patient cohorts. Specifically, Barcelo applies the protocol to 9,938 samples (abstract) which demonstrates the benefit of cryopreservation in large population-based cohort studies.
Claims 1 and 5-11 are rejected under 35 U.S.C. 103 as being unpatentable over Elgueta et al. Front Immunol. May 2019 (of record) in view of Oertel et al. J. Neurochem. 2016.
The teachings of Elgueta as they apply to Claims 1 and 5-9 are outlined above. Elgueta teaches that DRD3 expression was significantly reduced in Parkinson’s disease patients as compared to healthy controls which can be a useful marker for diagnostic analysis, but Elgueta fails to teach wherein the diagnosed subject is administered a Parkinson’s therapy (Claim 10) such as a dopamine agonist, a MAO-B inhibitor, a COMT inhibitor, or amantadine (Claim 11).
However, Oertel teaches that standard treatments for Parkinson’s disease comprise administering a dopamine agonist, a MAO-B inhibitor, a COMT inhibitor, or amantadine (abstract).
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to modify the method of detecting DRD3 expression in PBMCs to diagnose Parkinson’s disease as taught by Elgueta to further include treating the diagnosed patients with known Parkinson’s disease therapies as taught by Oertel. One of ordinary skill would understand that if a patient is diagnosed with Parkinson’s disease, the standard course of action is to administer therapies known to treat Parkinson’s disease. The motivation to administer therapies known to treat Parkinson’s disease is to ameliorate the disease or symptoms thereof in the diagnosed patients.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
1. Claims 1-2 and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 12 of copending U.S. App. No. 18/580,710.
The instant claims are directed to a method of detecting a level of tyrosine hydroxylase (TH) in a biosample from a subject wherein the biosample comprises PBMCs (Claims 1-2) or a homogenate of peripheral monocytes (Claim 20). The method of detection can be any technique known in the art (Claim 20) or specifically flow cytometry (Claims 1-2).
The copending claims are directed to a method for detecting a level of tyrosine hydroxylase (TH) in a biosample from a subject wherein the biosample comprises a homogenate of peripheral monocytes (Claims 1 and 12). The method of detection can be any technique known in the art (Claim 12) or specifically an ELISA assay (Claim 1). Note, it is understood that PBMCs comprise peripheral monocytes.
Because the copending claims recite the same elements of the instant claims, the methods of the instant claims are either anticipated and/or rendered obvious by the copending claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/SARAH COOPER PATTERSON/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675