DETAILED ACTION
Claims 114,116,118-123 and 129-142 are pending.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 06/03/2024 and 07/17/2026 have been considered by the examiner.
Claim Objections
Claims 114, 116, 118-123, and 129-142 are objected to because of the following informalities: claims 114, 116, 118-123, and 129-142 recite the abbreviation/acronym “NF-kB” which should be spelled out at their first usage followed by the abbreviation/acronym in parenthesis. Appropriate correction is required.
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.
1.Claims 114, 116, 118-123, and 136-142 are rejected under 35 U.S.C. 101 because the claimed product and method are directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Step 1
This part of the eligibility analysis evaluates whether the claim falls within any statutory
category per MPEP 2106.03.
Regarding instant claims 114, 116, 118-123, and 136-142, 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 114, 116, 118-123, and 129-142.
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).
A. Similarly, instant claims 114 and 137-139 are directed to a method of measuring naturally occurring proteins and correlating the measurements with the effectiveness of a treatment for Parkinson’s Disease (STEP 1: YES).
B. Similarly, instant claims 116 and 140-142 are directed to a method of measuring naturally occurring proteins and correlating the measurements to the effectiveness of a treatment for Parkinson’s Disease (STEP 1: YES).
C. Similarly, instant claims 118-123 and 136 are directed to a method of measuring naturally occurring proteins and correlating the measurements with the progression of Parkinson’s Disease during treatment (STEP 1: YES).
Step 2A, Prong 1: Does the claim recite a judicial exception?
This part of the eligibility analysis evaluates whether the claim recites a judicial
exception. As explained in MPEP 2106.04(II) and the October 2019 Update, a claim “recites” a
judicial exception when the judicial exception is “set forth” or “described” in the claim.
Regarding instant claims 114, 116, 118-123, and 136-142, 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 114, 116, 118-123, and 129-142.
Regarding claim 1 in 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.
A. Similarly, instant claim 114 recites measuring naturally occurring biomarkers NK-kB and/or calcineurin and correlating the measurements to the effectiveness of a treatment for Parkinson’s Disease, which is considered a law of nature. Further, instant claim 114 recites “c) (i) determining if the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of treatment decreased compared to the baseline expression level or (ii) comparing the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of treatment to the baseline expression level, wherein the comparison indicates a likelihood of therapeutic efficacy for the treatment of PD in the subject and/or indicates a degree of effectiveness at treating PD in the subject”, which is directed toward an abstract idea that falls under the mental process grouping (i.e., concepts performed in the human mind (including an observation, evaluation, judgement, opinion). Comparing collected information to a predetermined threshold, which is an act of evaluating information that can be practically performed in the human mind. Consequently, instant claim 114 recites the judicial exception of applying and using a law of nature and an abstract idea.
B. Similarly, instant claim 116 recites measuring naturally occurring biomarkers NK-kB and/or calcineurin and correlating the measurements to the effectiveness of a treatment for Parkinson’s Disease, which is considered a law of nature. Further, instant claim 116 recites “c) (i) determining if the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment decreased compared to the baseline expression level or (ii) comparing the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment compared to the baseline expression level, wherein the comparison indicates a likelihood of slowing, reversing, and/or halting the progression of PD in the subject” which is directed toward an abstract idea that falls under the mental process grouping (i.e., concepts performed in the human mind (including an observation, evaluation, judgement, opinion). Comparing collected information to a predetermined threshold, which is an act of evaluating information that can be practically performed in the human mind. Consequently, instant claim 116 recites the judicial exception of applying and using a law of nature and an abstract idea.
C. Similarly, instant claim 118 recites measuring naturally occurring biomarkers NK-kB and/or calcineurin and correlating the measurements to the efficacy of a treatment for Parkinson’s Disease, which is considered a law of nature. Further, instant claim 118 recites “d) (i) continuing treatment with the therapeutic agent if the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment decreased compared to the baseline expression level, or (ii) altering treatment if the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment did not decrease compared to the baseline expression level, wherein a decrease in the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment decreased compared to the baseline expression level indicates an increased likelihood of therapeutic efficacy in treating PD in the subject”, which is directed toward an abstract idea that falls under the mental process grouping (i.e., concepts performed in the human mind (including an observation, evaluation, judgement, opinion). Comparing collected information to a predetermined threshold, which is an act of evaluating information that can be practically performed in the human mind. Consequently, instant claim 118 recites the judicial exception of applying and using a law of nature and an abstract idea.
Step 2A Prong 2: Does the claim recite additional elements that integrate the exception into a practical application?
In 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.
A. Similarly, instant claim 114 does not have additional elements that would integrate the judicial exception cited above into a practical application. In comparison to claim 1, Example 43 did not pass step 2A prong 2 with a step of general treatment. Instant claim 114 does not recite a specific treatment step. Instant claim 114 recites looking at levels of specific biomarkers in response to a treatment and thus is not considered a treatment step.
Example 43 failed with a step of a general treatment, instant claim 114 does not recite a further active step, let alone a treatment.
B. Similarly, instant claim 116 does not have additional elements that would integrate the judicial exception cited above into a practical application. In comparison to claim 1, Example 43 did not pass step 2A prong 2 with a step of general treatment. Instant claim 116 does not recite a specific treatment step. Instant claim 116 recites looking at levels of specific biomarkers in response to a treatment to monitor the progression of disease and thus is not considered a treatment step.
C. Similarly, instant claim 118 does not have additional elements that would integrate the judicial exception cited above into a practical application. In comparison to claim 1, Example 43 did not pass step 2A prong 2 with a step of general treatment. Instant claim 118 does not recite a specific treatment step. Instant claim 118 recites looking at levels of specific biomarkers in response to a treatment to determine the efficacy of a treatment and thus is not considered a treatment step.
Dependent claims 119-123 and 136-142 do not have additional elements that would integrate the judicial exception into a practical application.
Step 2B: Does the claim recite significantly more?
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.
A. Similarly, instant claim 114 recites “a) determining a baseline expression level of NF-kB and/or calcineurin in a biological sample from a subject having PD; b) determining an expression level of NF-kB and/or calcineurin in a biological sample from the subject at one or more time points following initiation of treatment with a therapeutic agent” which recite mere instructions of obtaining a judicial exception and cannot be considered an inventive concept. Further, instant claim 114 recites “c) (i) determining if the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of treatment decreased compared to the baseline expression level or (ii) comparing the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of treatment to the baseline expression level, wherein the comparison indicates a likelihood of therapeutic efficacy for the treatment of PD in the subject and/or indicates a degree of effectiveness at treating PD in the subject” which recites simply observing the naturally occurring proteins, which does not amount to significantly more. Lastly, the recitation of administering a treatment amounts to nothing more than identifying a correlation and then “applying it” since the treatment step is recited at the highest level of generality (STEP 2B: NO).
B. Similarly, instant claim 116 recites “a) determining a baseline expression level of NF-kB and/or calcineurin in a biological sample from a subject having PD prior to initiation of a treatment comprising a therapeutic agent; b) determining an expression level of NF-kB and/or calcineurin in a biological sample from the subject at one or more time points following initiation of the treatment” which recite mere instructions of obtaining a judicial exception and cannot be considered an inventive concept. Further, instant claim 116 recites “c) (i) determining if the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment decreased compared to the baseline expression level or (ii) comparing the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment compared to the baseline expression level, wherein the comparison indicates a likelihood of slowing, reversing, and/or halting the progression of PD in the subject” which recites simply observing the naturally occurring proteins, which does not amount to significantly more. Lastly, the recitation of administering a treatment amounts to nothing more than identifying a correlation and then “applying it” since the treatment step is recited at the highest level of generality (STEP 2B: NO).
C. Similarly, instant claim 118 recites “a) determining a baseline expression level of NF-kB and/or calcineurin in a biological sample from a subject having PD; b) administering a therapeutic agent for the treatment of PD to the subject; c) determining an expression level of NF-kB and/or calcineurin in a biological sample from the subject at one or more time points following initiation of the treatment”, which recite mere instructions of obtaining a judicial exception and cannot be considered an inventive concept. Further, instant claim 118 recites
“ d) (i) continuing treatment with the therapeutic agent if the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment decreased compared to the baseline expression level, or (ii) altering treatment if the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment did not decrease compared to the baseline expression level, wherein a decrease in the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment decreased compared to the baseline expression level indicates an increased likelihood of therapeutic efficacy in treating PD in the subject” which recites simply observing the naturally occurring proteins, which does not amount to significantly more. Lastly, the recitation of administering a treatment amounts to nothing more than identifying a correlation and then “applying it” since the treatment step is recited at the highest level of generality (STEP 2B: NO).
Dependent claims 119-123 and 136-142 do not amount significantly more than a judicial exception. The limitations are merely data gathering steps that are directed towards the judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Accordingly, Dependent claims 119-123 and 136-142 are not eligible (STEP 2B: NO).
Thus, instant claims 114, 116, 118-123, and 136-142 are rejected under 35 USC 101.
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.
2.Claims 114, 116, 118-123, and 137-142 are rejected under 35 U.S.C. 103 as being unpatentable over Dziesietnik et al., (US 20190212344A1) (list of references cited filed on 05/19/2026), in view of Pizzi et al., (US 20170003302A1) (IDS filed on 07/17/2026).
Instant claim 114 recites “A method of determining the efficacy of a therapeutic agent for the treatment of Parkinson's Disease (PD), the method comprising: a) determining a baseline expression level of NF-kB and/or calcineurin in a biological sample from a subject having PD; b) determining an expression level of NF-kB and/or calcineurin in a biological sample from the subject at one or more time points following initiation of treatment with a therapeutic agent; and c) (i) determining if the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of treatment decreased compared to the baseline expression level or (ii) comparing the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of treatment to the baseline expression level, wherein the comparison indicates a likelihood of therapeutic efficacy for the treatment of PD in the subject and/or indicates a degree of effectiveness at treating PD in the subject.”.
Instant claim 116 recites “A method of monitoring the progression of Parkinson's Disease (PD) during treatment, the method comprising: a) determining a baseline expression level of NF-kB and/or calcineurin in a biological sample from a subject having PD prior to initiation of a treatment comprising a therapeutic agent; b) determining an expression level of NF-kB and/or calcineurin in a biological sample from [[a]]the subject at one or more time points following initiation of the treatment; and c) (i) determining if the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment decreased compared to the baseline expression level or (ii) comparing the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment compared to the baseline expression level, wherein the comparison indicates a likelihood of slowing, reversing, and/or halting the progression of PD in the subject.”
Instant claim 118 recites “A method for treating Parkinson's Disease (PD) in a subject, the method comprising: a) determining a baseline expression level of NF-kB and/or calcineurin in a biological sample from a subject having PD; b) administering a therapeutic agent for the treatment of PD to the subject; c) determining an expression level of NF-kB and/or calcineurin in a biological sample from the subject at one or more time points following initiation of the treatment; and d) (i) continuing treatment with the therapeutic agent if the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment decreased compared to the baseline expression level, or (ii) altering treatment if the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment did not decrease compared to the baseline expression level, wherein a decrease in the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment decreased compared to the baseline expression level indicates an increased likelihood of therapeutic efficacy in treating PD in the subject.”
Dziesietnik teaches a method of assessing the efficacy of a therapeutic agent in the
treatment of Parkinson’s Disease (PD) and monitoring the progression of PD (see claims 1 and 3 of ‘344, see [0008]), the method comprising:
a) determining a baseline expression level of a peripheral biomarker in a biological sample from a subject having PD (see [0054]);
b) determining an expression level of the peripheral biomarker in a biological sample from the subject at one or more time points following initiation of treatment with a therapeutic agent (see [0014]); and
c) (i) determining if the expression level of the peripheral biomarker at the one or more time points following initiation of treatment decreased compared to the baseline expression level or (ii) comparing the expression level of the peripheral biomarker at the one or more time points following initiation of treatment to the baseline expression level, wherein the comparison indicates a likelihood of therapeutic efficacy for the treatment of PD in the subject and/or indicates a degree of effectiveness at treating PD in the subject, and where the comparison indicates a likelihood of slowing, reversing, and/or halting the progression of PD (see claim 1 of ‘344, see [0012], see [0020], see [0036]) (instant claims 114, 116, and 118). Dziesietnik teaches (i) continuing treatment with the therapeutic agent if the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment decreased compared to the baseline expression level, or (ii) altering treatment if the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment did not decrease compared to the baseline expression level, wherein a decrease in the expression level of NF-kB and/or calcineurin at the one or more time points following initiation of the treatment decreased compared to the baseline expression level indicates an increased likelihood of therapeutic efficacy in treating PD in the subject (see claims 1 and 22-24 of ‘344) (instant claim 118).
Dziesietnik teaches wherein the altering comprises administering a different therapeutic agent (see [0063]) (instant claim 119). Dziesietnik teaches one or more time points following initial treatment with the therapeutic agent comprises a time point at or about two months following treatment (see [0058]) (instant claims 121-122, 138, and 141). Dziesietnik teaches the expression level being determined mass spectrometry, ELISA, or PCR (see [0021], see [0053]) (instant claims 123, 139, and 142).
Dziesietnik teaches wherein the baseline expression level is determined before treatment (see [0060]). While Dziesietnik does not explicitly teach that the baseline expression level is determined at or at least 1 day before treatment, it would have been obvious to one of ordinary skill in the art at the time of the instant application to perform routine optimization for determining when the baseline expression level sample needs to be done. Thus, absent demonstration of unexpected results of the claimed parameter, this optimization of when the sample is taken, would have been obvious at the time of the invention (instant claims 120, 137, and 140).
As noted in In re Aller, 105 USPQ 233 at 235, More particularly, where the general
conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or
workable ranges by routine experimentation.
Routine optimization is not considered inventive, and no evidence has been presented that determining when the initial baseline expression sample will be measured was anything other than routine, and should be considered unexpected in any way as compared to the closest prior art.
While Dziesietnik teaches measuring peripheral biomarkers, and NF-kB is a peripheral biomarker, Dziesietnik does not explicitly teach measuring NF-kB.
Pizzi teaches measuring NF-kB in patients who have Parkinson’s Disease (see [0010]) (instant claims 114, 116, 118, 123, 139, and 142).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the methods of determining response to treatment of Parkinson’s Disease taught by Dziesietnik with the method of diagnosing Parkinson’s Disease in a patient taught by Pizzi. Pizzi teaches that NF-kB can be detected in peripheral blood cells (see [0010]). Pizzi teaches that NF-kB is a credible peripheral biomarker for Parkinson’s Disease (see [0039]). It would have been obvious to one of ordinary skill in the art to determine the efficacy of a Parkinson’s Disease treatment by measuring NF-kB because as Pizzi teaches, it is a credible biomarker for PD and the increase or decrease of NF-kB will help determine if the treatment is effective or not. The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed.
3.Claims 129-131 and 133-136 are rejected under 35 U.S.C. 103 as being unpatentable over Dziesietnik and Pizzi as applied to claims 114, 116, 118-123, and 137-142 above, in view of Mosley et al., “A Synthetic Agonist to Vasoactive Intestinal Peptide Receptor-2 Induces Regulatory T Cell Neuroprotective Activities in Models of Parkinson's Disease.” Frontiers in cellular neuroscience vol. 13 421. 18 Sep. 2019, doi:10.3389/fncel.2019.00421.
The teachings of Dziesietnik and Pizzi as they pertain to claims 114, 116, 118-123, and 137-142 are discussed in the 35 USC 103 rejection above.
Dziesietnik does not teach the therapeutic being VIP or VIP2R, the use of an immunogen, or the biological sample being peripheral blood lymphocytes and/or T-cells.
Mosley teaches the therapeutic being a vasoactive intestinal peptide (see abstract, see page 2) (instant claim 129), and a peptide agonist of VIP2R (see abstract teaching the use of LBT-3627, a agonist of VIPR2) (VIP2R and VIPR2 are the same) (instant claim 130-131). Mosley teaches the GM-CSF is a sargramostim (see page 15 “Underscoring the translational potential of VIPR2 agonism is suggested by the demonstration that those downstream signaling outcomes via GM-CSF have successfully been tested in clinical trials of PD wherein sargramostim-treated patients showed increased Treg numbers and function, augmented motor neuronal activity, and improved UPDRS III scores”) (instant claim 133). Mosley teaches the therapeutic is an immunogen that induces a humoral immune response against at least one abnormal protein of PD and that immunogen is nitrated alpha synuclein (see page 2 “Moreover, that co-transfer of VIP-induced Tregs with nitrated-a-Syn specificTh17 Teffs to MPTP intoxicated recipient mice provided greater levels of neuroprotection than non-induced Tregs, and that adoptive transfer of LBT-3627-induced Tregs afforded greater neuroprotection than VIP-induced Tregs, highlight the potential importance of VIPR2 agonists as a putative treatment for neurodegenerative disorders.”) (instant claims 134-135). Mosley teaches the biological sample comprising peripheral blood lymphocytes and/or T-cells (see page 6 under “Multiple doses of VIPR2 agonists increases Treg activity without expanding CD4+ T cells or Tregs”, see page 4 under “Treg function assessment”) (instant claim 136).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the methods of determining response to treatment of Parkinson’s Disease taught by Dziesietnik with the method of diagnosing Parkinson’s Disease in a patient taught by Pizzi, with the Parkinson’s treatment taught by Mosley. Mosley teaches that in Parkinson’s Disease VIP elicits significant dopaminergic neuroprotective responses (see page 2). Mosley teaches that VIP is up-regulated in neuroimmune cells after injury and VIP also affects inflammatory response cascades, including mononuclear phagocytes and T cells by inhibiting production or release of inflammatory cytokines such as tumor necrosis factor alpha and interferon-gamma (see page 2). Mosley further teachers that the neuroprotective and immunomodulatory actions of VIP support the idea for the development of VIP receptors as therapeutic targets for neurodegenerative diseases (see page 2). Mosley teaches that VIPR2 agonists protects dopaminergic neurodegeneration and attenuates neuroinflammation induced by α-syn overexpression (see page 8). The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed.
4.Claims 132 is rejected under 35 U.S.C. 103 as being unpatentable over Dziesietnik and Pizzi as applied to claims 114, 116, 118-123, and 137-142 above, in view of Martinez et al., “A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases.” International journal of molecular sciences vol. 21,1 65. 20 Dec. 2019, doi:10.3390/ijms21010065.
The teachings of Dziesietnik and Pizzi as they pertain to claims 114, 116, 118-123, and 137-142 are discussed in the 35 USC 103 rejection above.
Dziesietnik does not teach the therapeutic agent being a mimetic vasoactive intestinal peptide (VIP).
Martinez teaches wherein the therapeutic agent is a mimetic of VIP and the agent reacts with a VIP receptor (see page 21 teaching the use of Aviptadil, a known mimetic of VIP that reacts with VIP receptors) (instant claim 132).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the methods of determining response to treatment of Parkinson’s Disease taught by Dziesietnik with the method of diagnosing Parkinson’s Disease in a patient taught by Pizzi, with the Parkinson’s Disease treatment method by Martinez. Martinez teaches that VIP/receptors are a novel therapeutic for PD (see page 18). Martinez teaches that VIP (also referred to as VPAC) has been shown to lead to changes in the microenvironment of the affected brain with oxidative stress, inflammation, and defective protein folding (see page 19), further, VIP2 has been shown to increase Treg activity without altering cell numbers, reduce microglial inflammatory responses, increase survival of dopaminergic neurons, and improve striatal densities (see page 19). The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed.
Conclusion
No claim is allowed.
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/MCKENZIE A DUNN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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