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
This application claims priority to the U.S. National Stage (371) application of PCT/US20/23080 filed on 03/17/2020 which claims priority to U.S. Provisional Application No. 62/819,745 filed on 03/18/2019.
Claim Status
Claims 1, 3-11, 18, 20-26 and 33-34 and 36-38 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/25/2025.
Claims 2 and 19 are cancelled at the Applicant’s request.
Claims 12-13 and 27 are currently amended and the Applicant notes that no new matter is added. Claims 14-17 and 28-32 are original.
Claim 35 of the claim set of 03/25/2025 is removed without any notes and the numbering of claims 36-38 of claim set of 03/25/2025 is changed by the Applicant to 35-37 without any notes.
Thus, claims 12-17 and 27-32 are pending and are under examination.
Specification
The disclosure is objected to because of the following informalities: Please write out all abbreviations before using them the first time. For example, please replace CRTH2 with “chemoattractant receptor homologue expressed on Th2 cells (”CRTH2”)”. Appropriate correction is required.
Claim Objections
The amendments to claims 12-13 and 27 are not proper since they do not comply with 37 C.F.R. § 1.121(c)(2), which states, "All claims being currently amended in an amendment paper shall be presented in the claim listing, indicate a status of 'currently amended,' and be submitted with markings to indicate the changes that have been made relative to the immediate prior version of the claims. The text of any added subject matter must be shown by underlining the added text. The text of any deleted
matter must be shown by strike-through except that double brackets placed before and after the
deleted characters may be used to show deletion of five or fewer consecutive characters. The text of
any deleted subject matter must be shown by being placed within double brackets if strike-through
cannot be easily perceived." See also, 37 C.F.R. § 1.121(c)(4)(ii), which states, “Cancellation of a
claim shall be effected by an instruction to cancel a particular claim number. Identifying the status of
a claim in the claim listing as 'canceled' will constitute an instruction to cancel the claim.” In the
instance case, claims 12-13 and 27 are currently amended without stating the type of amendments (i.e., addition or deletion). Thus, the original text and deleted text has not been properly identified.
Furthermore, claim 35 of the claim set of 03/25/2025 is removed without any notes on whether the claim is cancelled or withdrawn, and the numbering of claims 35-37 of the instant application is not in accordance with 37 CFR 1.126 which requires the original numbering of the claims to be preserved throughout the prosecution. When claims are canceled, the remaining claims must not be renumbered. When new claims are presented, they must be numbered consecutively beginning with the number next following the highest numbered claims previously presented (whether entered or not).
However, in the interest of advancing prosecution, current claims of 08/20/2025 are being examined and the misnumbered claims 35-37 of the instant application have been renumbered to 36-38 as in the original disclosure.
The Applicant is further advised to correct the amendments to comply with 37 C.F.R. § 1.121(c)(2) in the reply to the instant Office action.
Claim Interpretation
The Applicant has confirmed in the reply of 08/20/2025 that the maximum heart rate is a calculated value and recites that is the largest within-visit posture-induced difference (Pages 1-2 of Remarks of 08/20/2025, “The amendment defines the calculation and locks the protocol (supine after 2:10-min rest; upright at 2/5/10-min; tilt or active-stand) and expressly states it is the largest within-visit posture-induced difference”.
Maintained and New Rejections
Claim Rejections - 35 USC § 112(a)
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 12-17 and 27-32 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 CRTH2 or DP2 expression in subsets of T cells in patients with Postural Orthostatic Tachycardia Syndrome (POTS), it does not reasonably provide enablement for treating POTS with any CRTH2 antagonists. 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 use the invention commensurate in the broad scope with these claims.
In re Vaeck, 947 F.2d 488,495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991), the Court ruled that a rejection under 35 U.S.C. 112, first paragraph for lack of enablement was appropriate given the relatively incomplete understanding in the biotechnological field involved, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims. Such is the case where there is a relatively incomplete understanding in the biotechnological field involved, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims. In the instant case, the use of CRTH2 antagonists to treat patients for POTS is not well understood and is not documented in the prior art.
The current disclosure does not satisfy the enablement requirement for treating a patient with POTS with CRTH2 antagonists that are not commonly used for treating POTS and whether any necessary experimentation is "undue as discussed In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The breadth of the claims:
Claim 12 recites “A method of treating a Postural Orthostatic Tachycardia Syndrome (POTS) patient in need thereof, comprising: measuring a first heart rate while the patient is supine after at least 10 minutes of supine rest; measuring heart rates at 2, 5, and 10 minutes after the patient assumes an upright posture during a tilt-table test or active-stand test; calculating a "maximum heart-rate gap," defined as the largest difference (bpm) between the supine heart rate and each of the upright heart rates measured at 2, 5, and 10 minutes; identifying a patient having a maximum heart-rate gap ≥ 30 bpm; and administering to the identified patient an effective amount of an antagonist of CRTH2, thereby reducing the maximum heart-rate gap or improving orthostatic symptoms. Similarly claim 27 recites “A method of treating a Postural Orthostatic Tachycardia Syndrome (POTS) patient, comprising: identifying a POTS patient having a maximum heart-rate gap ≥ 30 beats per minute as defined in claim 12; and administering to the patient an effective amount of an antagonist of prostaglandin D2 receptor 2 (CRTH2), thereby reducing the maximum heart-rate gap or improving orthostatic symptoms”.
Claims 12 and 27 recite using a CRTH2 antagonist without specifying what type of antagonist to use. CRTH2 antagonists are small molecules that get tested as noted by Singh et al. (CRTH2 antagonists in asthma: current perspectives, Clinical Pharmacology: Advances and Applications, 2017:9 165- 173, page 168, left column, third paragraph, “Small-molecule antagonists of the CRTH2 receptor designed for oral administration have been synthesized, with some showing sufficient potency in preclinical studies to warrant evaluation in asthma clinical trials”). A small molecule is a protein, a lipid or any entity that binds to its receptor with high specificity and affinity. Thus, claims 12 and 27 read on treating a POTS patient with any CRTH2 antagonist and the claims are recited at a high level of generality.
The nature of the invention:
The instant application is for treating a patient for POTS with CRTH2 antagonists. POTS is commonly treated with either nonpharmacological approaches such as increasing aerobic exercise or with pharmacological agents such as β-blocking agents as noted by Johnson et al. (Postural Orthostatic Tachycardia Syndrome: A Clinical Review, Pediatr Neurol, 2010;42:77-85.Abstract). Furthermore, the common management of POTS patients does not mention the use of CRTH2 antagonists as noted by Fedorowski et al. (Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management, Journal of Internal Medicine, 2019, 285; 352-366, Epub 2018 Nov 23, page 361, Table 5, “The most widely used empirical therapeutic options in postural orthostatic tachycardia syndrome”).
Thus, treating a POTS patient with CRTH2 antagonists is different from the common practice in treating POTS patients as cited in the prior art above.
The state of the prior art:
The prior art teaches using CRTH2 antagonist to treat patients for asthma as noted by Singh et al. (Abstract) and for allergies as noted by Jandl et al. (The therapeutic potential of CRTH2/DP2 beyond allergy and asthma, Prostaglandins and Other Lipid Mediators 133 ( 2017) 42-48Abstract). Although Jandl mentioned that there might be a potential therapeutic use of CRTH2 to numerous conditions beyond allergic diseases and asthma, it falls short of indicating any role of CRTH2 in cardiac diseases such as in POTS.
Thus, the prior art does not discuss treating POTS patients with CRTH2 antagonists.
The level of one of ordinary skill:
The prior art teaches using CRTH2 to treat allergic diseases and asthma as noted by Jandl et al. (Abstract) and Pettipher et al. (Antagonism of the prostaglandin D2 receptors DP1 and CRTH2 as an approach to treat allergic diseases, Nature Reviews, Drug Discovery, Volume 6, April 2007, pages 313-325, Abstract).
Jandl teaches that blocking CRTH2 is a potential therapeutic approach to numerous conditions beyond classical allergic disease and asthma (Abstract). Jandl teaches that CRTH2 is involved in diseases of the central nervous system, kidney, intestine, lung , hair, skin , bone, cartilage and cancer (Abstract; Page 46, Fig 1. “CRTH2/DP2-mediated effects beyond allergic inflammation and asthma”). Jandl does not teach using CRTH2 antagonists to treat a patient for POTS.
Pettipher teaches the role of DP1 and CRTH2 receptors in allergic inflammation (Page 315, right column, “Role of DP1 and CRTH2 in allergic inflammation”). Pettipher teaches the recent progress in the discovery and development of selective antagonists of DP1 and CRTH2 receptors (Abstract). Pettipher teaches Identifying selective CRTH2 antagonists (Page 320, right column, “Identifying selective CRTH2 antagonists”). Pettipher teaches the presence of structural classes of CRTH2 antagonists (Page 321, right column, “Structural classes of CRTH2 antagonists”). Pettipher does not teach using CRTH2 antagonists to treat a patient for POTS.
Because the prior art does not teach using CRTH2 antagonists to treat patients for POTS, a skilled artisan would not have known how to treat POTS patients with which CRTH2 antagonist nor what dose and treatment regimen to use. Asthma and POTS are two diseases with different pathogenic pathways and outcomes, and a person of ordinary skill in the art would not have been able to know the proper treatment regimen and dose for treating a patient for POTS. Similarly, allergic diseases and POTS have different pathogenic pathways and outcomes.
Lastly, there is no common structure and mechanism of action among the different classes of CRTH2 antagonists as noted above by Pettipher (Pages 321-323, Structural classes of CRTH2 antagonists). In the instant case, the inventor proposed three classes of CRTH2 antagonist that do not share a common structure, and the skilled artisan would not have known which class to start with first to treat a patient for POTS.
The level of predictability in the art:
The prior art does not teach a person of ordinary skill in the art on how to treat a patient for POTS with any CRTH2 antagonist as shown in the management of POTS by Fedorowski et al. (Page 361, Table 5).
Federowski teaches how to diagnose a patient for POTS (Abstract; page 354, left column, second paragraph, “Diagnostic criteria of POTS”; page 358, Table 4, “Diagnostic modalities recommended in the workup of patient with suspected POTS diagnosis”). Federowski teaches that the pathophysiology of POTS is complex (Page 356, right column, second paragraph, “The aetiology of POTS”). Federowski teaches how to manage and treat a patient for POTS (Pages 359-360, “The management of POTS”). Federowski does not teach using CRTH2 antagonists to treat a patient for POTS.
Furthermore, it is not known yet how will different CRTH2 antagonists affect the treatment response in patients with POTS. In the instant application, the Applicant claimed using first any CRTH2 antagonist and then claimed three agents (Fevipiprant, setipiprant and CT133). However, it is not known how will be the response of a patient with POTS to any of the proposed agents. There are no pharmacokinetic studies to show the response of a patient with POTS to any CRTH2 antagonist.
Thus, there is a high level of unpredictability in the art because treating POTS patients with CRTH2 antagonists has not been documented as a common practice in prior art.
The amount of direction provided by the inventor:
The inventor only provided directions on how to look for the expression of CRTH2 on CD4 T cells and maximum heart rate gap which is a hallmark of POTS (Specification, Example 1). Similarly, the inventor only teaches a second example of the overall expression of CRTH2 in POTS patients (Specification, Example 2). Last the inventor only teaches two more examples for the expression of relevant surface antigens (Specification, Examples 3 and 4). None of the four examples teach how to treat a patient for POTS with any CRTH2 antagonist.
Furthermore, the method of treating POTS using any antagonist is not specified i.e., route of administration of antagonist, dose of antagonist and treatment regimen for the antagonist. Also, it is not clear by what is meant by “effective amount” in the claims. While CRTH2 has been found to be expressed in different cell types and in different tissues, its role is still being investigated as noted by Jandl et al. (Abstract, “we propose that blocking CRTH2 might be a potential therapeutic approach to numerous conditions beyond classical allergic diseases and asthma.”; page 43, left column, “CRTH2 has been found to be expressed on several additional cell types and in different tissues suggesting that the PGD2/ CRTH2 axis might be of potential relevance beyond allergy and asthma”).
Thus, the inventor provided no examples or guidelines for an artisan on how to treat a patient for POTS with any CRTH2 antagonist.
The existence of working examples:
The working examples that the inventor has provided in the specification are for the expression of CRTH2 on subsets of T cells but not for treating a POTS patient with any CRTH2 antagonist (Specification, Examples 1-4).
None of the four examples that are cited above teach treating a POTS patient with any CRTH2 antagonist. Example 1 of the specification of the instant application only teaches the expression of CRTH2 on CD4 T cells and maximum heart rate gap which is a hallmark of POTS (Pages 5-6, Example 1). Example 2 of the instant application only teaches the overall expression of CRTH2 in POTS patients (Page 6, Example 2). Examples 3 and 4 teach the expression of relevant surface antigens (Pages 6-7, Examples 3 and 4). Thus, the inventor does not provide any working examples for treating a POTS patient with any CRTH2 antagonist.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
As noted above, the inventor provided no examples or guidelines for an artisan on how to treat a patient for POTS with any CRTH2 antagonist. The inventor only provided examples for the expression of CRTH2 on a subset of T cells and correlated the expression with POTS (Specification, Examples 1-4). Examples 1-4 of the instant case do not teach how to treat a POTS patient with any CRTH2 antagonist. Furthermore, the prior art falls short of teaching how to use CRTH2 for treating POTS patients.
Thus, there will be an undue amount of experimentation to be done by the skilled artisan based on the state of prior art and inventor’s guidelines of the instant case.
The specification fails to disclose at least one method for using the claimed invention that bears a reasonable correlation to the entire scope of the claim, and thus the enablement requirement of 35 U.S.C. 112 is not satisfied. In the instant case, the specification teaches detecting CRTH2 on the surface of cells in POTS patients, however, it does not disclose any methods for treating patients for POTS with any CRTH2 antagonists.
Claim Rejections - 35 USC § 112(b)
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 12-17 and 27-32 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.
Regarding claims 12 and 27, the phrase "effective amount" renders the claim indefinite because it is unclear what amount is considered to be effective.
Per MPEP 2173.05(c), the common phrase “an effective amount” may or may not be indefinite. The proper test is whether or not one skilled in the art could determine specific values for the amount based on the disclosure. The phrase “an effective amount” has been held to be indefinite when the claim fails to state the function which is to be achieved and more than one effect can be implied from the specification or the relevant art. See In re Halleck, 422 F.2d 911, 164 USPQ 647 (CCPA 1970). In the instant case, the claims do not state a specific value of the CRTH2 antagonist as an effective amount to achieve a specific function. Furthermore, the specification does not list any effects that are implied from using a specific value of the CTRH2 antagonist as an effective amount. Last, the prior art does not teach what specific values of CRTH2 antagonist are considered to be an “effective amount” to treat a POTS patient as noted above.
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 12-14 and 27-29 are rejected under 35 U.S.C. 101 because the claimed invention is for a process or a method that is directed to at least one judicial exception without significantly more. The claims recite a mere collection of information in the form of data that is compared to a cutoff value from which the applicant or doctor will be able to predict the possibility of treating a patient for POTS with a CRTH2 antagonist. Such an inference is not sufficient to transform the abstract idea of a mathematical calculation of a maximum heart rate gap, the abstract idea of a mental process of a comparison with assessment and a conditional treatment step into a patentable application.
The claims are ineligible because the claims recite at least one judicial exception, i.e., abstract idea of a mathematical calculation (maximum heart rate gap in the POTS patient) and an abstract idea of a mental process (assessing the maximum heart rate gap a patient and comparing it to a cutoff value to identify a patient of having POTS). Moreover, the claims as a whole do not integrate the judicial exceptions into a practical application nor do they provide an inventive concept. The proposed treatment is too broad and general to require a doctor do something appropriate for the cancer patient because a particular treatment is not required, i.e., the treatment can be one of CRTH2-antagonists (fevipiprant, setipiprant or CT-133). Furthermore, the treatment step in the claims is still conditional because a POTS patient is not treated with a CRTH2 antagonist unless the patient has been identified to qualify for such treatment based on the cutoff value of maximum heart rate gap.
Step 1: Is the claim to a process, machine, manufacture or composition of matter?)
This part of the eligibility analysis evaluates whether the claim falls within any statutory category per MPEP 2106.03.
Example 43 of “2019 PEG” is particularly enlightening because the fact pattern of claim 1 of example 43 is most similar to the instant application claims.
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 1, the claim is directed to a process, which is one of the statutory categories of invention as the claim recites “A treatment method comprising: (a) calculating a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder phenotype; (b) administering a treatment to the patient having a non-responder phenotype.” (Step 1: YES).
Similarly, claims 12 and 27 of the instant application are also directed to a statutory class of a method of treating a Postural Orthostatic Tachycardia Syndrome (POTS) patient “A method of treating a Postural Orthostatic Tachycardia Syndrome (POTS) patient … measuring a first heart rate … measuring heart rates … calculating a "maximum heart-rate gap,", identifying a patient having a maximum heart-rate gap … administering to the identified patient an effective amount of an antagonist of CRTH2” (Step 1: YES).
(Step 2A, Prong 1: Does the claim recite an abstract idea, law of nature or natural phenomenon?)
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 2A, prong 1, the claim recites the judicial exception of “calculating a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder phenotype,” and according to broadest reasonable interpretation (BRI), an arithmetic calculation of a division is required to obtain the ratio of C11 to C13 that can be used to identify whether the patient has the non-respondent phenotype.
Specifically, limitation (a) in claim 1 of Example 43 of the “2019 PEG” recites “calculating a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder phenotype,” which has a BRI that requires performing an arithmetic calculation (division) in order to obtain the ratio of C11 to C13 levels, and then using this ratio to identify whether the patient has the non-responder phenotype (i.e., the patient has a calculated ratio of 3:1 or greater and thus is not responding, or will not respond, to glucocorticoids). This limitation therefore recites a mathematical calculation. The grouping of “mathematical concepts” in the 2019 PEG includes “mathematical calculations” as an exemplar of an abstract idea. 2019 PEG Section I, 84 Fed. Reg. at 52. Thus, limitation (a) falls into the “mathematical concept” grouping of abstract ideas. In addition, this type of simple arithmetic calculation (division) can be practically performed in the human mind, and is in fact performed in the human mind on a daily basis, for instance by school-aged children studying mathematics. Note that even if most humans would use a physical aid (e.g., pen and paper, a slide rule, or a calculator) to help them complete the recited calculation, the use of such physical aid does not negate the mental nature of this limitation. Thus, limitation (a) also falls into the “mental process” groupings of abstract ideas.
In addition, limitation (a) describes a naturally occurring relationship between the ratio of C11 to C13 and the non-responder phenotype, and thus may also be considered to recite a law of nature. Accordingly, limitation (a) recites a judicial exception (an abstract idea that falls within the mathematical concept and mental process groupings in the “2019 PEG”, and a law of nature), and the analysis must therefore proceed to Step 2A Prong Two.
Similarly, claims 12 and 27 of the instant application recites a judicial exception of calculating a “maximum heart rate gap” after measuring the heart rate and according to the broadest reasonable interpretation, an arithmetic calculation of a subtraction is also required to obtain the maximum heart rate gap which is used in claims 12 and 27 to qualify a POTS patient for treatment with a CRTH2 antagonist.
This limitation therefore recites a mathematical calculation which falls under an abstract idea as noted above in “2019 PEG”.
Furthermore, claims 12 and 27 are also reciting an abstract idea of a mental process of assessing the maximum heart rate gap of a patient and comparing it to a cutoff value to qualify a POTS patient for treatment with a CRTH2 antagonist “identifying a patient having a maximum heart-rate gap ≥ 30 bpm, and a law of nature of correlating largest difference in heart rate at different postures to treatment of POTS patients with CRTH2 antagonist “measuring a first heart rate while the patient is supine after at least 10 minutes of supine rest; measuring heart rates at 2, 5, and 10 minutes after the patient assumes an upright posture during a tilt-table test or active-stand test; calculating a "maximum heart-rate gap," defined as the largest difference (bpm) between the supine heart rate and each of the upright heart rates measured at 2, 5, and 10 minutes; identifying a patient having a maximum heart-rate gap ≥ 30 bpm; and administering to the identified patient an effective amount of an antagonist of CRTH2”
Last, similar to example 43 of the “2019 PEG” which is drawn to the calculation of a ratio of C11 to C13 levels in limitation (a), claims 12 and 27 of the instant application are also calculating the largest difference in heart rate at different postures to qualify a POTs patient for treatment with a CTRH2 antagonist. Thus, claims 12 and 27 of the instant application also describes a naturally occurring relationship between the largest difference in heart rate at different postures and qualifying a POTs patient for treatment with a CTRH2 agent, and thus are considered to recite a law of nature.
Accordingly, claims 12 and 27 of the instant application recite three judicial exceptions of an abstract idea that falls within the mathematical concept, a mental process and a law of nature, and the analysis must therefore proceed to Step 2A Prong Two.
(Step 2A, Prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application?)
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 2A, prong 2, the claim as a whole does not integrate the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. Besides the abstract idea, the claim 1 of example 43 of the “2019 PEG” recites the additional element of “(b) administering a treatment to the patient having a non-responder phenotype”. Although this limitation indicates that a treatment is to be administered, it does not provide any information as to how the patient is to be treated, or what the treatment is, but instead covers any possible treatment that a doctor decides to administer to the patient. In fact, this limitation is recited at such a high level of generality that it does not even require a doctor to take the calculation step’s outcome (the patient’s
phenotype) into account when deciding which treatment to administer, making the limitation’s inclusion in this claim at best nominal. Thus, limitation (b) of example 43 of the “2019 PEG” fails to meaningfully limit the claim because it does not require any particular application of the recited calculation, and is at best the equivalent of merely adding the words “apply it” to the judicial exception. Accordingly, limitation (b) of example 43 of the “2019 PEG” does not integrate the recited judicial exception into a practical application and the claim is therefore directed to the judicial exception.
Similarly, claims 12 and 27 of the instant application do not have additional elements that would integrate the judicial exceptions cited above into a practical application. The claims added step of administering treatment with a CRTH2 antagonist, and this step does not integrate the judicial exception into a practical application because they are data gathering steps to use in the calculation and comparison, which do not add a meaningful limitation to the method as they are insignificant extra-solution activity. These steps do not integrate the judicial exceptions into a practical application because they do not amount to more than the judicial exceptions themselves, analogous to Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 80, 84, 101 USPQ2d 1961, 1968-69, 1970 (2012). Furthermore, the claims do not act on or use the judicial exceptions in any further steps as required by MPEP 2106.04(d). Furthermore, similar to the conditionality of treatment of claim 1 of example 43 of the “2019 PEG”, claims 12 and 27 of the instant application have a treatment step that is conditional. In the instant case, claims 12 and 27 of the instant application have a conditional treatment step based on the value of the maximum heart-rate gap that does not provide any information as to how the patient is to be treated, or what the treatment regimen is, but instead covers any possible CRTH2 antagonist that a doctor decides to administer to the patient. In fact, this limitation is recited at such a high level of generality and conditionality that it does not even require a doctor to take action if the maximum heart rate gap is not greater than or equal to the cutoff value.
Therefore, claims 12 and 27 does not integrate the judicial exception into a practical application.
(Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?)
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 2B, this part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05. As explained with respect to Step 2A Prong Two, the claim recites a single additional element in limitation (b), which does not require any particular application of the recited calculation and is at best the equivalent of merely adding the words “apply it” to the judicial exception. Mere instructions to apply an exception cannot provide an inventive concept (Step 2B: NO). The claim is not eligible.
Similarly, claims 12 and 27 of the instant application also recite a conditional general treatment step with any CRTH2 antagonist to the judicial exception which does not amount to more than the judicial exception itself. Furthermore, the claim itself is recited at a high level of generality in which any CRTH2 antagonist can be used as the treatment method for claims 12 and 27.
Thus, claims 12 and 27 are not eligible and is rejected under 35 USC 101.
Regarding claim 13, the claim specifies the age of the POTS patient, provides a conditional treatment “treated when” and an additional judicial exception of an abstract idea of a comparison “when the maximum heart rate gap is greater than or equal to 40 beats per minute” which do not integrate the judicial exception into a practical application, nor do they amount to significantly more.
Regarding claims 14 and 29, the claim specifies the condition of the POTS patient which does not integrate the judicial exception into a practical application, nor does it amount to significantly more.
Similar to claim 13, claim 28 specifies the age of the POTS patient and the maximal heart rate gap which do not integrate the judicial exception into a practical application, nor do they amount to significantly more.
Response to Arguments
Applicant's arguments filed on 08/20/2025 have been fully considered but they are not persuasive.
Objection to Specification:
The Applicant alleged that the first uses of CRTH2/DP2 are expanded to resolve the abbreviation objection in the Remarks of 08/20/2025. However, the Applicant did not provide a new copy of the specification with such amendments to the Office. Furthermore, the Applicant is expected to provide for examination a disclosure that is free of any minor typographical or punctuation errors.
The Applicant authorized the Examiner in the Remarks of 08/20/2025 to amend the specification for any minor typographical or punctuation errors. However, to preserve the intended invention of the instant application and to prevent any alteration to the inventive concept of the original disclosure, any amendments to the original disclosure are to be made by the Applicant of the instant application.
Thus, the previous objection to the specification is still maintained and is made final.
Rejection of claims 12-17 and 27-32 under 35 U.S.C. 112(a)
The Applicant alleged that “the specification enables the full scope of the elected claims under Wands without requiring undue experimentation”.
This argument is not persuasive because the specification, while being enabling for detecting CRTH2 or DP2 expression in subsets of T cells in patients with Postural Orthostatic Tachycardia Syndrome (POTS), it does not reasonably provide enablement for treating POTS with CRTH2 antagonists such as with fevipiprant, setipiprant or with CT133. The specification admits that CRTH2 antagonists are used to treat allergies and asthma (Page 4, [17]). However, the specification states that CRTH2 antagonist can be used to treat POTS without providing a rationale for such a use nor a treatment regimens and dose (Page 4, [17]). 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 use the invention commensurate in scope with these claims.
The current disclosure does not satisfy the enablement requirement for treating a patient with POTS with CRTH2 antagonists that are not commonly used for treating POTS and whether any necessary experimentation is "undue as discussed In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The method of treatment in claims 12 and 27 is not specified i.e., route of administration, dose and treatment regimen. Also, it is not clear by what is meant by “effective amount” in the language of claims 12 and 27. While CRTH2 has been found to be expressed in different cell types and in different tissues, its role is still being investigated as noted by Jandl et al. (Abstract, “we propose that blocking CRTH2 might be a potential therapeutic approach to numerous conditions beyond classical allergic diseases and asthma.”; page 43, left column, “CRTH2 has been found to be expressed on several additional cell types and in different tissues suggesting that the PGD2/ CRTH2 axis might be of potential relevance beyond allergy and asthma”). Thus, treating a POTS patient with CRTH2 antagonists is different from the common practice in treating POTS patients as cited in the prior art above.
In re Vaeck, 947 F.2d 488,495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991), the Court ruled that a rejection under 35 U.S.C. 112, first paragraph for lack of enablement was appropriate given the relatively incomplete understanding in the biotechnological field involved, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims. Such is the case where there is a relatively incomplete understanding in the biotechnological field involved, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims. In the instant case, the use of CRTH2 antagonists to treat patients for POTS is not well understood and is not documented in the prior art.
The prior art teaches using CRTH2 to treat allergic diseases and asthma as noted by Jandl et al. (Abstract) and Pettipher et al. (Abstract).
Because the prior art does not teach using CRTH2 to treat patients for POTS, a skilled artisan would not have known how to treat POTS patients with a CRTH2 antagonist nor what dose and treatment regimen to use. Asthma and POTS are two diseases with different pathogenic pathways and outcomes, and a person of ordinary skill in the art would not have been able to know the proper treatment regimen and dose for treating a patient for POTS. Similarly allergic diseases and POTS have different pathogenic pathways and outcomes.
Thus, the previous rejection of claims 12-17 and 27-32 under 35 U.S.C. 112(a) for enablement is maintained and is made final.
Rejection of claims 12-14 under 35 U.S.C. 101:
The Applicant alleged that the claims do not stop at measuring/calculating and a conditional "maybe treat". The Applicant further alleged that the claims require: (i) clinically obtaining specific physiologic measurements by a defined protocol; (ii) identifying a patient having the defined threshold; and (iii) administering a particular class of drugs (CRTH2 antagonists) to produce a clinical improvement ("thereby reducing . . . "). The Applicant further alleged that the "conditional" wording is removed by reciting administration to a patient having the threshold.
This argument is not persuasive because the recited steps of measuring the heart rate of a POTS patient in different positions and calculating maximum heart rate gap to compare to a cutoff value to qualify a POTS patient for treatment with a CRTH2 antagonist do not integrate the judicial exception into a practical application because they are data gathering steps to use in the calculation and comparison, which do not add a meaningful limitation to the method as they are insignificant extra-solution activity. These steps do not integrate the judicial exceptions into a practical application because they do not amount to more than the judicial exceptions themselves, analogous to Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 80, 84, 101 USPQ2d 1961, 1968-69, 1970 (2012). Furthermore, the claims do not act on or use the judicial exceptions in any further steps as required by MPEP 2106.04(d). Last, similar to claim 1 of example 43 of the “2019 PEG”, claims 12 and 27 of the instant application have a treatment step that is conditional. Claims 12 and 27 of the instant application still have a conditional treatment step “identifying a patient having a maximum heart-rate gap ≥ 30 bpm” that does not provide any information as to how the patient is to be treated, or what the treatment regimen is, but instead covers any possible CRTH2 antagonist that a doctor decides to administer to the patient. In fact, this limitation is recited at such a high level of generality and conditionality that it does not even require a doctor to take action if the maximum heart rate gap is not greater than or equal to the cutoff value.
Thus, the previous rejection of claims 12-14 under 35 U.S.C. 101 is maintained and is made final.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/OMAR RAMADAN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678