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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2/20/2026 has been entered.
Claim Status and formal matters
The instant action is in response to papers filed 2/20/2026.
The non-final action of 6/9/2025 provides rejection for the genus claims by providing art on a specific species encompassed by the broad claims. The response of 8/22/2025 has amended the previously generic claims to a different species of pathological state. Thus the instant amendment is considered to limit the generic claims to species of pathological state and provides new species, which are the reason for the instant species election. Any future amendment to change the pathological state will be considered a new invention.
Clams 15-16 and 18 are amended.
Claims 15-16 and 18 are being examined.
Election/Restrictions
Applicant’s election without traverse of damage to cartilage tissue and formation of cartilage tissue in the reply filed on 10/242025 is acknowledged. However, after searching this species election has been withdrawn.
Applicant’s election without traverse of 1) a therapeutic product exerting its therapeutic effect as Product D and (ii) biological samples from patients treated with a therapeutic comparator reference product, the biological samples comprising cancer cells. Claims 15-18 read on such species in the reply filed on 5/19/2025 is acknowledged.
Priority
The instant application was filed 12/05/2024 and is a divisional of 18744862 , filed 06/17/2024.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/20/2026 is being considered by the examiner. The NPL is marked through as it is not provided.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Response to Amendment
The declaration filed by Dr. Lucci under 37 CFR 1.132 filed 2/20/2026 is insufficient to overcome the rejection of pending claims based upon 112(a), 112(b), 101 and art as set forth in the last Office action because:
Written description Arguments
The declaration traverses the written description rejection by “. Example 2 of the specification describes cell-based assays representative of osteoarthritis. These protocols are also clearly described on pages 79-85 using Product A (Arté GX), a natural matrix comprising Centella asiatica leaves and Echinacea purpurea flowers coextracted in water demonstrates written description. This argument has been thoroughly reviewed but is not considered persuasive as example 2 is limited to primary human chondrocytes to Centella asiatica leaves and Echinacea purpurea flowers coextracted in water and gene expression is determined.
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Thus this example does not teach identifying hallmarks, identifying one or more modulated biological activities, prior to the contacting step. Further the example does not specifically teach human chondrocytes with an osteoarthritic and human chrondcytes with a non-osteoarthritic phenotype (and not treated with IL1B. Further the cited example is a single species of primary human chondrocytes, a single species of natural raw source material, does not specifically teaching step (b) or (c).
The declaration continues by arguing example 10 on page 111 (this appears to be page 113) the declaration asserts, “As explained, the quali-quantitative modulation values for each biological activity were calculated in terms of z-scores and the values compared and reported in Figures 1-4. A skilled artisan would understand that there is adequate description in the art as well as the specification to identify assays that measure the effects of compounds on the formation of cartilage tissue, inflammation of joints, and non-traumatic arthropathy.” This argument has been thoroughly reviewed but this appears to merely be a replication of example 2 and the cited example is a single species of primary human chondrocytes, a single species of natural raw source material, does not specifically teaching step (b) or (c).
The declaration in point 8 asserts, “:Product A regulates a state because at least 50% of the biological activities for each hallmark are modulated by each batch according to the modulation trend representative of the health state and the modulation values calculated for each of said at least 50% of the biological activities differ at least 15% from the respective modulation values calculated for the pathological state control. In fact, Figures 2-4 show that all of the biological activities identified for each hallmark are modulated according to the modulation trend that concurs to a healthy state (shown in Figure 1).” This argument has been thoroughly reviewed but is not considered persuasive as this appears to be further replication of example 2 and cited example is a single species of primary human chondrocytes, a single species of natural raw source material, does not specifically teaching step (b) or (c).
The declaration continues by providing arguments about the formation of cartilage. This argument has been thoroughly reviewed but is not considered but the claims are not limited to formation of cartilage as the biological activity. Thus the single species does not demonstrate possession of any biological activity in any human chondrocyte. Thus the claims lack adequate written description.
112(b) Arguments
The declaration begins by asserting, “First, a skilled artisan would easily understand the differences between human chondrocytes having an osteoarthritis or normal phenotype. These are not relative terms, but the specification even provides a number of hallmarks associated with osteoarthritis at pages 79-82 and 85.” This argument has been thoroughly reviewed but is not considered persuasive as the understanding of skilled artisan is opinion of the inventor who has a vested interest in the outcome the application. With respect to the arguments of claims 79-82 these appear to provide teachings obtained by Ingenuity Pathway Analysis (IPA) and provide key words to interrogate IPA and chosen biological function. However, this does not demonstrate what is required of chondrocytes have an osteoarthritic phenotype an and chondrocytes have a non-osteoarthritic phenotype. The teachings of example 2 appear to use primary human chondrocytes. Thus example 2 does not provide how to differentiate the two. The declaration also cites page 85 which is a table and does not provide a standard or definition of what is required of chondrocytes have an osteoarthritic phenotype an and chondrocytes have a non-osteoarthritic phenotype.
The declaration further alleges pages 79-85 and figures 2-4 clearly provide how calculations are done. This argument has been thoroughly reviewed but are not considered persuasive as review of the cited portions of the specification and figures as originally filed fail to provide any specific formulas or calculations. While some of the figures provide numbers the figures do not explicitly teach how the calculations were done.
101 Arguments
The declaration begins by arguing, “In my understanding, the claimed invention provides a specific technical solution of identifying an anti-osteoarthritis therapeutic product that exerts its effect to treat a disease or pathophysiological condition through a physiological mechanism of action, wherein the therapeutic product comprises at least one natural matrix derived from plant extracts. Moreover, the claims require that modulation of hallmarks from inflammatory processes, cellular proliferation, anatomical damage, and oxidative stress in human chondrocytes is determined by transcriptomic analysis and the therapeutic products are identified by applying a mathematical formula.” This argument has been thoroughly reviewed but is not considered persuasive as the argument appears to concede the method uses naturally occurring correlation of gene expression with treatment and mental step or abstract idea of mathematical formula (it is noted the claims do not explicitly provide a mathematical formula).
The declaration continues by alleging, “while the claims may be directed to a judicial exception, which I do not concede, the claims are integrated into a practical application. The recited experimental procedures are specifically applied before mathematical operations are applied to the gathered data to generate more accurate information about the object than was previously possible in the art. Moreover, the claims describe in detail the step-by-step method for accomplishing the physical process from contacting the chondrocytes with the therapeutic product, to contacting the treated cells with interleukin 1B, and then a transciptomic analysis.” This argument has been thoroughly reviewed but is not considered persuasive as the inventor has merely provide his interpretation of the claim. The declarant has failed to identify any limitation which integrates, depends from, or otherwise applies the judicial exception.
The declaration concludes arguments with respect to 101 by asserting, “These claimed elements are provided in an ordered combination and as such provide an unconventional arrangement that yields technical improvements to the claimed methods that were not conventional in the field. While the assays were known, the Office does not provide any evidence to suggest that the particular combination of assays, along with the mathematical operations, was conventional at the time.” This argument has been thoroughly reviewed but is not considered persuasive as these appear to be opinion of the inventor as the declaration provides no evidence of provided in an ordered combination and as such provide an unconventional arrangement that yields technical improvements to the claimed methods that were not conventional in the field.
The declaration concludes the arguments by asserting, “Therefore, it is my opinion that the claims are patentable subject matter because they apply, but not claim, a natural relationship; they effect physical transformation; and they are narrow, specific, and leave the opportunity for others to practice the natural relationship through different biomarkers or detection methods without pre-empting the ability of others to practice the given natural relationship.” This argument has been thoroughly reviewed but is not considered persuasive as The response traverses the rejection asserting the claims do not preempt the use of other biomarkers. This argument has been thoroughly reviewed but is not considered persuasive as the Memo of May 4, 2016 Formulating a Subject Matter Eligibility Rejection and Evaluating the Applicant's Response to a Subject Matter Eligibility Rejection states, “If applicant argues that the claim is specific and does not preempt all applications of the exception, an appropriate response would be to explain that preemption is not a standalone test for eligibility. Questions of preemption are inherent in and resolved by the two-part framework from Alice Corp. and Mayo, as explained by the Federal Circuit in OJP and Sequenom. Moreover, while a preemptive claim may be ineligible, the absence of complete preemption does not demonstrate that a claim is eligible.” Further the sequencing does not transform anything, but merely provides data. Further In University of Utah Research v. Ambry Genetics the courts stated, “Recently in Alice the Supreme Court reiterated its two-step test to determine patent eligibility for any claims that allegedly encompass abstract ideas. First, “we determine whether the claims at issue are directed to [a] patent-ineligible concept[]. If so, we then ask, ‘what else is there in the claims before us?’” Id. at 2355 (quoting Mayo, 132 S. Ct. at 1296–97) (citations and punctuation omitted). That is, we next ask whether the remaining elements, either in isolation or combination with the other non- patent-ineligible elements, are sufficient to “‘transform the nature of the claim’ into a patent-eligible application.” Id. at 2355 (quoting Mayo, 132 S. Ct. at 1297). Put another way, there must be a further “inventive concept” to take the claim into the realm of patent eligibility.” Thus this argument is not persuasive.
Art Arguments
The declaration begins traversing the rejection in 22 by providing the inventors understanding of obviousness this is noted. The response continues by arguing, “I disagree with the Office's conclusion on the obviousness. There is nothing in the cited references that would direct a person of ordinary skill in the art to identify whether a product exeris its effect through a physiological mechanism of action. In fact, there is nothing in any of the references that teach or suggest any mechanism of action at all.” This argument has been thoroughly reviewed but is not considered persuasive as the specification provides no limiting definition of what is required of a physiological mechanism. Thus the broadest reasonable interpretation is any mechanism which occurs by any physiological standard, such as a signaling pathway.
The declaration continues by asserting, “Rasheed merely reports on the effect of EGCG on Cox-2 expression through upregulation of mIR expression. The authors suggest that these compounds could be useful to inhibit cartilage breakdown but provide no teaching that would lead a skilled artisan to the claimed method to identify a physiological mechanism of action.” This argument has been thoroughly reviewed but is not considered persuasive as the argument appears to concede EGCG regulates Cox-2 expression through the physiological mechanism of miroRNA expression.
The declaration continues by asserting, “Mu merely provides a review of how botanical drug extracts play a role in cartilage repair. Monagas discloses variability in botanical extracts. Abubakar reviews extraction techniques. Yimam merely reports on a botanical composition comprising two bioflavonoid extracts from the heartwood of A. catechu and the root bark of M. alba in monosodium-indoacetate-induced osteoarthritis as alternative remedy for management of the disease. And Soul discloses a survey of genes regulated in animal models of osteoarthritis. However, there is nothing in the combination of these teachings to arrive at the claimed method that particularly identifies physical processes that can be tied with mathematical analyses to identify products having a physiological mechanism of acting in the treatment of osteoarthritis.” This argument has been thoroughly reviewed but is not considered persuasive as The response further asserts that motivation to combine prior art references must be clear and particular. This argument has been thoroughly reviewed but is not considered persuasive as the Supreme Court in KSR INT’L CO. v. TELEFLEX INC states, “The obviousness analysis cannot be confined by a formalistic conception of the words teaching, suggestion, and motivation, or by overemphasis on the importance of published articles and the explicit content of issued patents. The diversity of inventive pursuits and of modern technology counsels against limiting the analysis in this way. In many fields it may be that there is little discussion of obvious techniques or combinations, and it often may be the case that market demand, rather than scientific literature, will drive design trends. Granting patent protection to advances that would occur in the ordinary course without real innovation retards progress and may, in the case of patents combining previously known elements, deprive prior inventions of their value or utility.” Thus the courts have held that explicit motivation need not be set forth in the prior art of record. As indicated in the rejection one of skill in the art would be motivated to examine any known physiological mechanism such as those cited in the prior art. Thus the rejection is maintained.
Priority
The instant application is filed 04/03/2025 is a Divisional of 18744862 , filed 06/17/2024. This application is filed as a divisional, as the parent application restricted between methods of assessing whether a beneficial product exerts its effect to treat disease and method of producing a therapeutic product. However, the instant claims while providing a preamble of producing a beneficial or therapeutic product, the steps are encompassed by the claims of the parent. Thus the claims do not appear to be a proper divisional. Similarly the claims of 18/970350 appear to have claims that are encompassed by the instant claims and thus does not appear to be a divisional.
Specification
The disclosure is objected to because of the following informalities:.
The clean copy of the specification filed 10/22/2025 on page 80 states: “Modulation of expressed genes were shown in different intensities of blue (signifying down-modulation) or red (signifying up-modulation). The resulting expected calculated” Thus it appears to the specification or drawings are in color, which is not allowed.
Page 79 provides a flow diagram. 37 CFR 1.58 states, “(a) The specification, including the claims, may contain chemical and mathematical formulae, but shall not contain drawings or flow diagrams.”
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required:
Claim 15 recites, “human chondrocytes having an osteoarthritic phenotype” and “human chondrocytes having a non-osteoarthritic physiological state.” Review and searching the specification did not reveal antecedent basis for these limitations.
Appropriate correction is required.
Response to Arguments
These are new grounds of objection.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 15-16 and 18 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 claim(s) contains 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.
MPEP 2163 IB New or amended claims section II
With respect to newly added or amended claims, applicant should show support in the original disclosure for the new or amended claims. See, e.g., Hyatt v. Dudas, 492 F.3d 1365, 1370, n.4 (Fed. Cir. 2007) (citing MPEP § 2163.04 which provides that a "simple statement such as ‘applicant has not pointed out where the new (or amended) claim is supported, nor does there appear to be a written description of the claim limitation ‘___’ in the application as filed’ may be sufficient where the claim is a new or amended claim, the support for the limitation is not apparent, and applicant has not pointed out where the limitation is supported."); see also MPEP §§ 714.02 and 2163.06 ("Applicant should ... specifically point out the support for any amendments made to the disclosure."); and MPEP § 2163.04
Claim 15 has been amended to recites: “A method for clinically validating the physiological mechanism of action of an anti-osteoarthritic product comprising at least one natural matrix derived from plant extracts, the method comprising: (1) identifying an anti-osteoarthritic product comprising at least one natural matrix derived from plant extracts by:(a) identifying hallmarks selected from arthralgia/arthritis, arthropathy, damage of cartilage tissue, inflammation and[[/or]] pain of joints that are representative of osteoarthritis;(b) identifying one or more modulated biological activities that underlie osteoarthritis selected from formation of cartilage tissue, inflammation of joint, and non-traumatic arthropathy, thereby providing a network of biological activities that are modulated in osteoarthritis;(c) identifying a set of markers that allow for evaluation of the biological activities that are modulated by the therapeutic product;(dl) contacting at least one control group of human chondrocytes and at least two test groups of human chondrocytes having an osteoarthritic phenotype relevant to the use of the therapeutic product with one or more different batches of said anti-osteoarthritis product; or (d2) contacting at least one group of human chondrocytes having a non-osteoarthriticnon-osteoarthritic physiological state with one or more different batches of said anti-osteoarthritis product; wherein the osteoarthritis induced is treatable by said anti-osteoarthritis product;(e) contacting primary human chondrocytes that have been treated with ILlB with Z [[or]] (d2), or (e) by transcriptomic analysis and calculating the respective modulation values or pattern for each of said biological activity;(g) comparing said modulation value or modulation pattern for each biological activity function in each cell group of step (f); and(h) identifying an anti-osteoarthritis product that exerts its therapeutic activity through a physiological mechanism when at least 50% of said one or more biological activities for each hallmark is at the same level as found in a healthy state, and the modulation values determined in (f) of each at least 50% one or more biological activities for said test groups of cells of (dl) differ, respectively, from the ones of said control groups of cells of (dl) by at least 0.15, or at least 50% of said one or more biological activities for each hallmark are modulated by each product batch with the modulation trend of the network concurring to the healthy state, and the modulation values determined in (f) of each of said at least 50% of one or more biological activities for said test groups of cells of (d2) differ, respectively, from the ones of said control group of cells of (d2) by at least 15%, and functional resilience of the anti-osteoarthritis product is demonstrated when the modulation values determined in (f) for each one or more biological activities of each of said test groups of cells differ by less than 20% from the average of said modulation values; and(2) subjecting at least two groups of biological test samples to one or more biological assays selected from gene expression analysis and transcriptomic analysis, wherein the biological samples are from (i) patients treated with the anti-osteoarthritis product that exerts its effect through a physiological mechanism of action, (ii) patients treated with a reference anti-osteoarthritis product, and[[/or]] (iii) patients treated with a placebo, wherein each of the at least two groups of samples are collected at different times V1 and Vn, n being an integer >1, wherein the groups of samples from (i)-(iii) are collected at the same times, and wherein the read-out of the gene expression analysis or transcriptomic analysis is representative of the modulation of one or more biological activities underlying the desired effect, and determining from said read out: whether said anti-osteoarthritis product exert its action by regulating a network of said biological activities that underly the osteoarthritis, and wherein,said anti-osteoarthritis product is clinically confirmed to exert its action through a physiological mechanism of action when said anti-osteoarthritis product is shown to regulate a network of said biological activities that underly the osteoarthritis.
The response merely asserts the specification as originally filed provides support for the amendment. However, review and searching of the specification did not reveal antecedent basis for this claim or dependent claims. The specification does not specifically teach the combination of limitations of the claims and does not appear to provide antecedent basis for “human chondrocytes having an osteoarthritic phenotype” and “human chondrocytes having a non-osteoarthritic physiological state.” Thus the claims appear to be new matter.
As set forth in In re Alonso 88 USPQ2d 1849 (Fed. Cir. 2008), at 1851:
The written description requirement of 35 U.S.C. § 112, ¶ 1, is straightforward: “The specification shall contain a written description of the invention ….” To satisfy this requirement, the specification must describe the invention in sufficient detail so “that one skilled in the art can clearly conclude that the inventor invented the claimed invention as of the filing date sought.” Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572 [41 USPQ2d 1961] (Fed. Cir. 1997); see also LizardTech, Inc. v. Earth Res. Mapping, Inc., 424 F.3d 1336, 1345 [76 USPQ2d 1724] (Fed. Cir. 2005); Eiselstein v. Frank, 52 F.3d 1035, 1039 [34 USPQ2d 1467] (Fed. Cir. 1995).
Alonso at 1852:
A genus can be described by disclosing: (1) a representative number of species in that genus; or (2) its “relevant identifying characteristics,” such as “complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.” Enzo, 323 F.3d at 964.
In applying the test as set forth in Alonso, it is noted that applicant is claiming “A method for clinically validating the physiological mechanism of action of an anti-osteoarthritic product comprising at least one natural matrix derived from plant extracts, the method comprising: (1) identifying an anti-osteoarthritic product comprising at least one natural matrix derived from plant extracts by:(a) identifying hallmarks selected from arthralgia/arthritis, arthropathy, damage of cartilage tissue, inflammation and[[/or]] pain of joints that are representative of osteoarthritis;(b) identifying one or more modulated biological activities that underlie osteoarthritis selected from formation of cartilage tissue, inflammation of joint, and non-traumatic arthropathy, thereby providing a network of biological activities that are modulated in osteoarthritis;(c) identifying a set of markers that allow for evaluation of the biological activities that are modulated by the therapeutic product;(dl) contacting at least one control group of human chondrocytes and at least two test groups of human chondrocytes having an osteoarthritic phenotype relevant to the use of the therapeutic product with one or more different batches of said anti-osteoarthritis product; or (d2) contacting at least one group of human chondrocytes having a non-osteoarthriticchondrocytes, and at least two test groups of human chondrocytes having a non-osteoarthritic physiological state with one or more different batches of said anti-osteoarthritis product; wherein the osteoarthritis induced is treatable by said anti-osteoarthritis product;(e) contacting primary human chondrocytes that have been treated with ILlB with Z [[or]] (d2), or (e) by transcriptomic analysis and calculating the respective modulation values or pattern for each of said biological activity;(g) comparing said modulation value or modulation pattern for each biological activity function in each cell group of step (f); and(h) identifying an anti-osteoarthritis product that exerts its therapeutic activity through a physiological mechanism when at least 50% of said one or more biological activities for each hallmark is at the same level as found in a healthy state, and the modulation values determined in (f) of each at least 50% one or more biological activities for said test groups of cells of (dl) differ, respectively, from the ones of said control groups of cells of (dl) by at least 0.15, or at least 50% of said one or more biological activities for each hallmark are modulated by each product batch with the modulation trend of the network concurring to the healthy state, and the modulation values determined in (f) of each of said at least 50% of one or more biological activities for said test groups of cells of (d2) differ, respectively, from the ones of said control group of cells of (d2) by at least 15%, and functional resilience of the anti-osteoarthritis product is demonstrated when the modulation values determined in (f) for each one or more biological activities of each of said test groups of cells differ by less than 20% from the average of said modulation values; and(2) subjecting at least two groups of biological test samples to one or more biological assays selected from gene expression analysis and transcriptomic analysis, wherein the biological samples are from (i) patients treated with the anti-osteoarthritis product that exerts its effect through a physiological mechanism of action, (ii) patients treated with a reference anti-osteoarthritis product, and[[/or]] (iii) patients treated with a placebo, wherein each of the at least two groups of samples are collected at different times V1 and Vn, n being an integer >1, wherein the groups of samples from (i)-(iii) are collected at the same times, and wherein the read-out of the gene expression analysis or transcriptomic analysis is representative of the modulation of one or more biological activities underlying the desired effect, and determining from said read out: whether said anti-osteoarthritis product exert its action by regulating a network of said biological activities that underly the osteoarthritis, and wherein,said anti-osteoarthritis product is clinically confirmed to exert its action through a physiological mechanism of action when said anti-osteoarthritis product is shown to regulate a network of said biological activities that underly the osteoarthritis.
The claims encompass human chondrocytes having an osteoarthritic phenotype, human chondrocytes having non-osteoarthritic physiological state, modulated biological activities that underlie osteoarthritis selected from formation of cartilage tissue, inflammation of joint, and non-traumatic arthropathy, thereby providing a network of biological activities that are modulated in osteoarthritis by osteoarthritis by any standard. The claims further encompass, anything which can be considered osteoarthritic phenotype relevant to the use of the anti-osteoarthritic product” The claims further encompass anything that can be considered ;(f) determining a modulation value or modulation pattern for each of said markers of step (c) on one or more of the cellular samples of steps (dl) or (d2) by transcriptomic analysis and calculating the respective modulation values or pattern for each of said biological activity;(g) comparing said modulation value or modulation pattern for each biological activity function in each cell group of step (f); and(h) identifying an anti-osteoarthritis product that exerts its therapeutic activity through a physiological mechanism when at least 50% of said one or more biological activities for each hallmark is at the same level as found in a healthy state, and the modulation values determined in (f) of each at least 50% one or more biological activities for said test groups of cells of (dl) differ, respectively, from the ones of said control groups of cells of (dl) by at least 0.15, or at least 50% of said one or more biological activities for each hallmark are modulated by each product batch with the modulation trend of the network concurring to the healthy state, and the modulation values determined in (f) of each of said at least 50% of one or more biological activities for said test groups of cells of (d2) differ, respectively, from the ones of said control group of cells of(d2) by at least 15%, and functional resilience of the anti-osteoarthritis product is demonstrated when the modulation values determined in (f) for each one or more biological activities of each of said test groups of cells differ by less than 20% from the average of said modulation values.”
The claim further recites, “{2) subjecting at least two groups of biological samples to one or more biological assays selected from gene expression analysis and transcriptomic analysis, wherein the biological samples are from (i) patients treated with the anti-osteoarthritis product that exerts its effect through a physiological mechanism of action, (ii) patients treated with a reference anti-osteoarthritis product, and/or (iii) patients treated with a placebo, wherein each of the at least two groups of samples are
The teachings of the specification are limited to a use of human primary chondrocytes but does not provide adequate written description for how the calculations are determining, identifying and comparing steps are down. Further the specification and claims lack support for the full the breadth of the claims.
Response to Arguments
The response begins traversing the rejection in view of the Declaration by Dr Lucci, by repeating the arguments from the declaration. This argument has been thoroughly reviewed but is not considered persuasive for the reasons of record.
It is noted the response does not specifically address the issues with respect to new matter.
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 15-16 and 18 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 15 is indefinite because it lacks a positive active step relating back to the preamble. The preamble recites method for clinically validating the physiological mechanism of action of an anti-osteoarthritic product comprising at least one natural matrix derived from plant extracts, however the last positive active step is drawn to {2) subjecting at least two groups of biological test samples to one or more biological assays selected from gene expression analysis and transcriptomic analysis. Therefore it is unclear as to whether the method for clinically validating the physiological mechanism of action of an anti-osteoarthritic product comprising at least one natural matrix derived from plant extracts or {2) subjecting at least two groups of biological test samples to one or more biological assays selected from gene expression analysis and transcriptomic analysis.
Claim 15 recites, “human chondrocytes having an osteoarthritic phenotype, human chondrocytes having non-osteoartritic physiological state.” The metes and bounds are unclear as to what the difference between human chondrocytes having an osteoarthritic phenotype and human chondrocytes having non-osteoartritic physiological state. Further it is unclear what is required by phenotype and physiological state as recited in the claim.
Claim 15 further recites, “ f) determining a modulation value or modulation pattern for each of said markers of step (c) on one or more of the cellular samples of steps (dl), (d2), or (e) by transcriptomic analysis and calculating the respective modulation values or pattern for each of said biological activity.” The claim is vague, unclear and incomplete as the claims and specification do not teach how this calculation is done.
Claim 15 recites, “) identifying an anti-osteoarthritis product that exerts its therapeutic activity through a physiological mechanism when at least 50% of said one or more biological activities for each hallmark is at the same level as found in a healthy state, and the modulation values determined in (f) of each at least 50% one or more biological activities for said test groups of cells of (dl) differ, respectively, from the ones of said control groups of cells of (dl) by at least 0.15.” The metes and bounds of “0.15” are unclear if it is a percentage, ratio, or something else as there are no units. Thus the claim is vague and unclear.
Claim 15 recites, “physiological mechanism of action.” The claim does not provide a limitation or standard of what is required. Review and searching of the specification revealed 32 recitations of “physiological mechanism of action.” Review of these recitation did not reveal a standard to differentiate “physiological mechanism of action” from “non-physiological mechanism of action.” Thus the metes and bounds are unclear what is included or excluded by the term.
Claim 15 recites, “functional resilience of the anti-osteoarthritis product is demonstrated when the modulation values determined in (f) for each one or more biological activities of each of said test groups of cells differ by less than 20% from the average of said modulation values.” The metes and bounds are unclear as this relies on modulation values which are indefinite for the reasons of record.
Claim 15 further recites, “(2)subjecting at least two groups of test biological samples to one or more biological assays selected from gene expression analysis and transcriptomic analysis, wherein the biological samples are from (i) patients treated with the anti-osteoarthritis product that exerts its effect through a physiological mechanism of action, (ii) patients treated with a reference anti-osteoarthritis product, and/or (iii) patients treated with a placebo, wherein each of the at least two groups of samples are collected at different times V1 and Vn, n being an integer >1, wherein the groups of samples from (i)-(iii) are collected at the same times. The claim is confusing and unclear as the claim recites, “and/or” between (ii) and (iii) and then latter appears to require all 3. Thus it is unclear what is required.
Claim 16 recites, “the product tested.” The metes and bounds are unclear how the as the claim does not previously recite, “product tested,” neither does the independent claim from which it depends. Thus it is unclear what product tested the limitation is referencing. .
Claim 18 recites, “comparing said modulation values for each of said one or more biological activities thereby providing an average modulation value for each of said activities for each of said groups of samples.” It is unclear how comparing provides an average modulation value. Further the claims appear to require only a single sample in each group, thus it is unclear how an average would be determined. Further the claims recites, “said one or more average biological activities or patient biological activities.” Patient biological activities is not previously recited and unclear what is required. Further the claim recites, ”the modulation trend of the network.” The claim does not previously recite modulation trend of the network, thus it is unclear what is being required. Further the claim recites V2, but the claims do not explicitly recite V2. Further the claim appears to be assuming V2 comes after V1, but that is not required of the claim.
Claim 18recites, of said at least 50% one or more average biological activities or patient biological activities differ, respectively, from the ones of V1 of at least 0.15.” The metes and bounds of “0.15” are unclear if it is a percentage, ratio, or something else as there are no units. Thus the claim is vague and unclear.
Response to Arguments
The response traverses the rejection in view of the amendment and arguments of the declaration. This argument has been thoroughly reviewed but is not considered persuasive for the reasons of record.
The response further asserts, “With respect to the Office's asserting that the metes and bounds of physiological mechanism of action is unclear, Applicant respectfully asserts that the specification at least at page 10, lines 20 - page 11, line 32 provides guidance as to the definition of physiological mechanism of action. Moreover, functional resilience is defined at page 28, line 35 of the specification. “ This argument has been thoroughly reviewed but is not considered persuasive as the cited portion teaches:
Physiological mode of action: The Medical Device (MD) EU Regulation 2017/745 (Regulation) officially published in Europe May on 5th, 2017 [REGULATION (EU) 2017/745 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC] and introduced a completely new governance into all aspects of the lifecycle of a MD. The term Medical Device, according to the Regulation, comprises products which do achieve a therapeutic effect but not with a pharmacological, immunological, or metabolic (Ph.IM) mode of action (MOA). The Ph.I.M MOA is the mode of action characterized by a key-lock model where the selected API obeys the rules of SAR and acts on its target receptor. In particular, the Regulation also indicates that a product which modifies a pathological or physiological state or process through a non-Ph-IM mechanism of action is a MD. It is noted that the MD regulation 2017/745, appears to refer to devices capable of modifying a physiological or pathological state, therefore, appears to extend the definition of medical devices to include products capable of interacting with the human body in such a way as to modify its state. The modification over time of a pathological or physiological state (e.g., an altered physiological state) results in the modification of a pathological or physiological process. It is therefore necessary to provide methods for assessing whether a therapeutic or beneficial product interacts with the human body in such a way as to modify a state as opposed as to merely modify a function, and to assess whether this state modification is ascribable to a physiological mechanism of action. Summarising, at the regulatory level it has become of great importance to establish whether a therapeutic product modifies one or few functions or a whole state and the mode of action by which the therapeutic effect is obtained. It is herein reminded that without marketing authorisation a therapeutical product cannot be produced and put into the market. In fact, although the regulations regarding medical devices vary by country or region, in many places, medical devices must undergo a regulatory approval process before they can be marketed or sold. This approval process typically involves demonstrating that the device is safe and effective for its intended use. It's essential for manufacturers to understand and comply with the regulatory requirements specific to the regions where they intend to market their medical devices to ensure legal market access and patient safety. The present evolution of the regulations (as discussed above) opens new scenarios for manufacturers that at present cannot be explored and exploited due to the absence of suitable tools for assessing and demonstrating the compliance with regulatory requirements. The present invention provides methods for assessing when a therapeutic or beneficial product consisting of one or more natural matrices, exerts its therapeutic or beneficial effect through a physiological mode of action, i.e., a non-Ph.I.M. mode of action. These methods solve a crucial practical problem that a manufacturer encounters when preparing the dossiers for the marketing authorisation of therapeutic or beneficial products as it allows to define whether said products fulfil the regulatory requirements set out e.g., by various existing Medical Device regulations and, in the affirmative, to support said fulfilment.
This argument has been thoroughly reviewed but is not considered persuasive as the cited portion may provide a preferred embodiment but does not specifically provide a definition of what is required.
The response further asserts page 28, line 35 defines functional resilience. The cited portion states:
Functional resilience according to the present description is intended as a therapeutic or beneficial (homeostasis adjuvant) resilience of a therapeutic or beneficial product comprising or consisting of one or more natural matrices; the term describes the maintenance of the therapeutic or beneficial properties of different batches of a given product comprising (or consisting of one or more natural matrices) notwithstanding the different batch to batch qualitative and quantitative composition, which is necessarily present (inherent) in products comprising or consisting of one or more natural matrices. As known by the skilled person, each time a different batch of starting raw material is used, the resulting natural matrix has a unique quali-quantitative composition at the molecular level which is typical of the individual diversity between living organisms also of the same species.
This argument has been thoroughly reviewed but is not considered persuasive as the attempt at a definition relies on resilience which as indicated in the reject is a relation term. Thus the metes and bounds are unclear.
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.
Claims15-16 and 18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation and mental step without significantly more. The claim(s) recite(s) the abstract idea or mental step of determining. Further the claim recites, “(1) identifying an anti-osteoarthritic product comprising at least one natural matrix derived from plant extracts by: (a) identifying hallmarks selected from arthralgia/arthritis, arthropathy, damage of cartilage tissue, inflammation and/or pain of joints that are representative of osteoarthritis; (b) identifying one or more modulated biological activities that underlie osteoarthritis selected from formation of cartilage tissue, inflammation of joint, and non- traumatic arthropathy, thereby providing a network of biological activities that are modulated in osteoarthritis; (c) identifying a set of markers that allow for evaluation of the biological activities that are modulated by the therapeutic product;” and “(f) determining a modulation value or modulation pattern for each of said markers of step (c) on one or more of the cellular samples of steps (dl)Z [[or]] (d2), or (e) by transcriptomic analysis and calculating the respective modulation values or pattern for each of said biological activity;(g) comparing said modulation value or modulation pattern for each biological activity function in each cell group of step (f); and(h) identifying an anti-osteoarthritis product that exerts its therapeutic activity through a physiological mechanism when at least 50% of said one or more biological activities for each hallmark is at the same level as found in a healthy state, and the modulation values determined in (f) of each at least 50% one or more biological activities for said test groups of cells of (dl) differ, respectively, from the ones of said control groups of cells of (dl) by at least 0.15, or at least 50% of said one or more biological activities for each hallmark are modulated by each product batch with the modulation trend of the network concurring to the healthy state, and the modulation values determined in (f) of each of said at least 50% of one or more biological activities for said test groups of cells of (d2) differ, respectively, from the ones of said control group of cells of (d2) by at least 15%, and functional resilience of the anti-osteoarthritis product is demonstrated when the modulation values determined in (f) for each one or more biological activities of each of said test groups of cells differ by less than 20% from the average of said modulation values; and(2) subjecting at least two groups of biological test samples to one or more biological assays selected from gene expression analysis and transcriptomic analysis, wherein the biological samples are from (i) patients treated with the anti-osteoarthritis product that exerts its effect through a physiological mechanism of action, (ii) patients treated with a reference anti-osteoarthritis product, and (iii) patients treated with a placebo, wherein each of the at least two groups of samples are collected at different times V1 and Vn, n being an integer >1, wherein the groups of samples from (i)-(iii) are collected at the same times, and wherein the read-out of the gene expression analysis or transcriptomic analysis is representative of the modulation of one or more biological activities underlying the desired effect, and determining from said read out: whether said anti-osteoarthritis product exert its action by regulating a network of said biological activities that underly the osteoarthritis, and wherein, said anti-osteoarthritis product is clinically confirmed to exert its action through a physiological mechanism of action when said anti-osteoarthritis product is shown to regulate a network of said biological activities that underly the osteoarthritis “ which are a natural laws or correlations and/or mental step/ abstract step. This judicial exception is not integrated into a practical application because if there is no step which depends from or otherwise integrates the judicial exception. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims provide no specific reagents or steps which provide for significantly.
Claim analysis
The instant claim 15 is directed towards A method for clinically validating the physiological mechanism of action of an anti-osteoarthritic product comprising at least one natural matrix derived from plant extracts, the method comprising: (1) identifying an anti-osteoarthritic product comprising at least one natural matrix derived from plant extracts by:(a) identifying hallmarks selected from arthralgia/arthritis, arthropathy, damage of cartilage tissue, inflammation and[[/or]] pain of joints that are representative of osteoarthritis;(b) identifying one or more modulated biological activities that underlie osteoarthritis selected from formation of cartilage tissue, inflammation of joint, and non-traumatic arthropathy, thereby providing a network of biological activities that are modulated in osteoarthritis;(c) identifying a set of markers that allow for evaluation of the biological activities that are modulated by the therapeutic product;(dl) contacting at least one control group of human chondrocytes and at least two test groups of human chondrocytes having an osteoarthritic phenotype relevant to the use of the therapeutic product with one or more different batches of said anti-osteoarthritis product; or (d2) contacting at least one group of human chondrocytes having a non-osteoarthriticnon-osteoarthritic physiological state with one or more different batches of said anti-osteoarthritis product; wherein the osteoarthritis induced is treatable by said anti-osteoarthritis product;(e) contacting primary human chondrocytes that have been treated with ILlB with said therapeutic product;(f) determining a modulation value or modulation pattern for each of said markers of step (c) on one or more of the cellular samples of steps (dl)Z (d2), or (e) by transcriptomic analysis and calculating the respective modulation values or pattern for each of said biological activity;(g) comparing said modulation value or modulation pattern for each biological activity function in each cell group of step (f); and(h) identifying an anti-osteoarthritis product that exerts its therapeutic activity through a physiological mechanism when at least 50% of said one or more biological activities for each hallmark is at the same level as found in a healthy state, and the modulation values determined in (f) of each at least 50% one or more biological activities for said test groups of cells of (dl) differ, respectively, from the ones of said control groups of cells of (dl) by at least 0.15, or at least 50% of said one or more biological activities for each hallmark are modulated by each product batch with the modulation trend of the network concurring to the healthy state, and the modulation values determined in (f) of each of said at least 50% of one or more biological activities for said test groups of cells of (d2) differ, respectively, from the ones of said control group of cells of (d2) by at least 15%, and functional resilience of the anti-osteoarthritis product is demonstrated when the modulation values determined in (f) for each one or more biological activities of each of said test groups of cells differ by less than 20% from the average of said modulation values; and(2) subjecting at least two groups of biological test samples to one or more biological assays selected from gene expression analysis and transcriptomic analysis, wherein the biological samples are from (i) patients treated with the anti-osteoarthritis product that exerts its effect through a physiological mechanism of action, (ii) patients treated with a reference anti-osteoarthritis product, and (iii) patients treated with a placebo, wherein each of the at least two groups of samples are collected at different times V1 and Vn, n being an integer >1, wherein the groups of samples from (i)-(iii) are collected at the same times, and wherein the read-out of the gene expression analysis or transcriptomic analysis is representative of the modulation of one or more biological activities underlying the desired effect, and determining from said read out: whether said anti-osteoarthritis product exert its action by regulating a network of said biological activities that underly the osteoarthritis, and wherein, said anti-osteoarthritis product is clinically confirmed to exert its action through a physiological mechanism of action when said anti-osteoarthritis product is shown to regulate a network of said biological activities that underly the osteoarthritis..
The identifying steps, determining, comparing, identifying are mental steps.
The wherein the readout clause and determining step are natural correlations or phenomenas and/or mental steps.
The subjecting to one or more biological assays of a nucleic acid is considered to be an active step requiring the analysis of a sample.
Dependent claims set forth further limitations to analysis of data and intended outcome of analysis and thus are also mental steps or abstract ideas and judicial exceptions.
According to the 2019 Patent Eligibility Guidance an initial two step analysis is required for determining statutory eligibility.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? In the instant case the Step 1 requirement is satisfied as the claims are directed towards a process.
Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, abstract idea and law of nature or natural phenomena and/or mental step.
With regards to claim 15, the claim recites, “(“(1) identifying an anti-osteoarthritic product comprising at least one natural matrix derived from plant extracts by: (a) identifying hallmarks selected from arthralgia/arthritis, arthropathy, damage of cartilage tissue, inflammation and/or pain of joints that are representative of osteoarthritis; (b) identifying one or more modulated biological activities that underlie osteoarthritis selected from formation of cartilage tissue, inflammation of joint, and non- traumatic arthropathy, thereby providing a network of biological activities that are modulated in osteoarthritis; (c) identifying a set of markers that allow for evaluation of the biological activities that are modulated by the therapeutic product;” and “(f) determining a modulation value or modulation pattern for each of said markers of step (c) on one or more of the cellular samples of steps (dl)Z [[or]] (d2), or (e) by transcriptomic analysis and calculating the respective modulation values or pattern for each of said biological activity;(g) comparing said modulation value or modulation pattern for each biological activity function in each cell group of step (f); and(h) identifying an anti-osteoarthritis product that exerts its therapeutic activity through a physiological mechanism when at least 50% of said one or more biological activities for each hallmark is at the same level as found in a healthy state, and the modulation values determined in (f) of each at least 50% one or more biological activities for said test groups of cells of (dl) differ, respectively, from the ones of said control groups of cells of (dl) by at least 0.15, or at least 50% of said one or more biological activities for each hallmark are modulated by each product batch with the modulation trend of the network concurring to the healthy state, and the modulation values determined in (f) of each of said at least 50% of one or more biological activities for said test groups of cells of (d2) differ, respectively, from the ones of said control group of cells of (d2) by at least 15%, and functional resilience of the anti-osteoarthritis product is demonstrated when the modulation values determined in (f) for each one or more biological activities of each of said test groups of cells differ by less than 20% from the average of said modulation values; and(2) subjecting at least two groups of biological test samples to one or more biological assays selected from gene expression analysis and transcriptomic analysis, wherein the biological samples are from (i) patients treated with the anti-osteoarthritis product that exerts its effect through a physiological mechanism of action, (ii) patients treated with a reference anti-osteoarthritis product, and (iii) patients treated with a placebo, wherein each of the at least two groups of samples are collected at different times V1 and Vn, n being an integer >1, wherein the groups of samples from (i)-(iii) are collected at the same times, and wherein the read-out of the gene expression analysis or transcriptomic analysis is representative of the modulation of one or more biological activities underlying the desired effect, and determining from said read out: whether said anti-osteoarthritis product exert its action by regulating a network of said biological activities that underly the osteoarthritis, and wherein, said anti-osteoarthritis product is clinically confirmed to exert its action through a physiological mechanism of action when said anti-osteoarthritis product is shown to regulate a network of said biological activities that underly the osteoarthritis.” These are an abstract ideas or mental steps and/or natural correlations.
Claim 18 recites, “comparing said modulation values for each of said one or more biological activities thereby providing an average modulation value for each of said activities for each of said groups of samples,effect through a physiological mechanism of action when at least 50% of said one or more average biological activities or patient biological activities for each hallmark are modulated in V2 with the modulation trend of the network concurring to the healthy state, and each of said modulation values of V2 determined of said at least 50% one or more average biological activities or patient biological activities differ, respectively, from the ones of V1 of at least 0.15.” This is a mental step and/or abstract idea and a natural phenomenon or natural correlation.
Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? The answer is no as there are no steps which depend from or otherwise integrate the judicial exception..
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No as the claim provides no steps which require any specific reagents or assay conditions.
With regards to claim 2 the claim requires a single active step of measuring the amounts of nucleic acids. The specification teaches:
the in vitro cell-based assay is an assay whose read out is associated to the pathological condition or altered physiological condition treated by the product under examination. In vitro cell-based assays are well-known laboratory techniques that involve the use of isolated cells to study biological processes or test the
effects of drugs, chemicals, or other substances. In the present invention, the in vitro cell-based assay used, is designed to simulate conditions related to the pathology or pathophysiological condition or to simulate conditions related to the altered physiological state. According to the invention, cell culture models such as monolayer cultures, or three-dimensional (3D) systems can be used. When appropriate, disease- specific cell lines can be used, depending on the disease of interest (e.g., cancer) also
proliferation assays can be used. (page 40)
.
Thus the claim does not provide additional steps which are significantly more.
Rasheed (J. Cell. Mol. Med. Vol 20, No 12, 2016 pp. 2241-2248) Mu ( Frontiers in Pharmacology (2022) pages 1-23), Monagas Frontiers in Pharmacoloty (2022) pages 1-10), Abubakar (. J Pharm Bioall Sci 2020;12:1-10), Yimam (JOURNAL OF MEDICINAL FOOD J Med Food 20 (6) 2017, 568–576), Soul (l. Ann Rheum Dis 2021;80:376–383)) demonstrate the active steps of the claims is routine and conventional.
Response to Arguments
The response traverses the rejection asserting, “Applicant respectfully disagrees that the claims recite limitations with respect to calculating and determining whjch appear to be vague, unclear, and incomplete. As explained by Dr. Lucci, the claimed invention provides a specific technical solution of producing an anti-osteoarthritis therapeutic product that exerts its effect to treat a disease or pathophysiological condition through a physiological mechanism of action, wherein the therapeutic product comprises at least one natural matrix derived from plant extracts. Moreover, the claims require that modulation of hallmarks from formation of cartilage tissue, inflammation of joint, and non-traumatic arthropathy in human chondrocytes is determined by transcriptomic analysis and the therapeutic products are identified by applying a mathematical formula.. “ This argument has been thoroughly reviewed but is not considered persuasive as the claim provides no specific mathematical formula, Further the claim provides no steps which integrate the judicial exception.
The response continues by asserting, “While the claims may be directed to a judicial exception, the claims are integrated into a practical application. The recited experimental procedures are specifically applied before mathematical operations are applied to the gathered data to generate more accurate information about the object than was previously possible in the art. Moreover, the claims describe in detail the step-by-step method for accomplishing the physical process from contacting the chondrocytes with the therapeutic product, to contacting the treated cells with interleukin 1B, and then a transciptomic analysis. These claimed elements are provided in an ordered combination and as such provide an unconventional arrangement that yields technical improvements to the claimed methods that were not conventional in the field. While the assays were known, the Office does not provide any evidence to suggest that the particular combination of assays, along with the mathematical operations, was conventional at the time.” This argument has been thoroughly reviewed but is not considered persuasive as the response concedes, “experimental procedures are specifically applied before mathematical operations are applied to the gathered data to generate more accurate information about the object than was previously possible in the art.” Thus suggesting the experimental steps are routine and conventional. The arguments with respect to stepwise nature of the claims is not persuasive as MPEP 2111.01 II states:
The problem is to interpret claims ‘in view of the specification’ without unnecessarily importing limitations from the specification into the claims."); Altiris Inc. v. Symantec Corp., 318 F.3d 1363, 1371, 65 USPQ2d 1865, 1869-70 (Fed. Cir. 2003) (Although the specification discussed only a single embodiment, the court held that it was improper to read a specific order of steps into method claims where, as a matter of logic or grammar, the language of the method claims did not impose a specific order on the performance of the method steps, and the specification did not directly or implicitly require a particular order).
Thus the broadest reasonable interpretation of the claims is the steps can be any order, except where the steps do not require impose a specific order by being dependent on the previous step.
Thus the rejection is maintained.
And 18
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.
Claim(s) 15-16 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rasheed (J. Cell. Mol. Med. Vol 20, No 12, 2016 pp. 2241-2248) Mu ( Frontiers in Pharmacology (2022) pages 1-23), Monagas Frontiers in Pharmacoloty (2022) pages 1-10), Abubakar (. J Pharm Bioall Sci 2020;12:1-10), Yimam (JOURNAL OF MEDICINAL FOOD J Med Food 20 (6) 2017, 568–576), Soul (l. Ann Rheum Dis 2021;80:376–383)
This rejection is presented in view of the numerous 112 (b) issues set forth above.
With regards to claim 15and 18, Rasheed teaches, “green tea, has gained significant attention among scientists and has now become one of the leading naturally derived polyphenols studied for its potential health benefits [12, 13]. A cup of green tea typically provides 60–125 mg catechins, including EGCG. EGCG has been shown to be 25–100 times more effective than vitamins C and E in terms of antioxidant activity [13]. Haqqi et al. performed extensive studies in the past decade and have verified the cartilage-preserving and chondro-protective action of EGCG [14–17]. We also have earlier shown that EGCG was non-toxic to human chondrocytes and inhibited the expression of inflammatory mediator’s in vitro [18]. Recently, several studies have revealed that dietary polyphenols including EGCG have the potential to modulate miRNAs expression in various cancer cells [19–23]. However, the effects of EGCG on miRNA expression in chondrocytes are unknown. Here, we have addressed the question for the first time of a possible regulatory effect of EGCG on miRNAs regulation in human chondrocytes. In this study, we determined that EGCG inhibits the IL-1b-induced COX-2 mRNA/protein expression via up-regulating the expression of microRNA hsa-miR-199a-3p in primary human OA chondrocytes. Our results thus identify a unique mechanism of action of a dietary constituent of green tea and suggest that use of EGCG or compounds derived from it may have cartilage sparing effect by miRNAs regulation in arthritis..” (page 2242, 1st column). Rasheed teaches the use of primary chondrocytes (Patients cartilage and preparation of chondrocytes. Rashee teaches the use of mutlipel batches of cells and/or EGCG by the use of error bars representing replication of samples.
Mu teaches, “In recent years, certain advancements have been made in the
treatment of OA with botanical drug remedies. In relevant meta-analyses, it has been found that botanical drug can relieve pain and improve the range of motion in patients with KOA (Cameron and Chrubasik, 2014), and the incidence of adverse reactions is low (Chen et al., 2016a). We searched in the PubMed database for “osteoarthritis,” “arthritis,” “tissue engineering,” “cartilage tissue engineering,” “biomaterials, Chinese herbal medicine,” “scaffolds,” “nanoparticles,” and “hydrogels.” Reviews, conference papers, and studies (those did not include both BDEs and carriers) were excluded. Finally, 31 related articles were selected through reading headlines, abstracts, and full texts. We then classified the BDEs in the literature (including flavonoids, polyphenols, alkaloids, saponins, and others). By summarizing the effect of plant drug extract combined with biomaterial carrier on the repair of OA cartilage injury, its mechanism, and current research status, we provide a theoretical basis for ideas and directions of future research” (page 4)
Monagas teaches, “The composition of botanical extracts from the same plant may vary significantly depending on the extraction solvent(s) used, the temperature and duration of extraction, and the processes used to dry the extracts. Other sources of variation include the steps taken to concentrate or remove targeted constituents or classes of constituents, and the compounds formed during extraction or further processing. Additional variation in the composition of botanical extracts made using the same plant species and plant part as starting materials may occur due to genetic factors, environmental conditions, and agricultural practices.”
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to screen multiple batches of botanical extracts by use of human primary chondrocytes to examine known hallmarks implicated in osteoarthritis including IL-1beta response. The artisan would be motivated as the art recognizes the variability within a botanical as well as the extraction method. The artisan would further be motivated to identify batches which mitigate hallmarks or pathways associated with osteoarthritis. The artisan would be motivated as the artisan is merely using known methods.
Abubakar teaches a review of preparation of medicinal plants: basic extraction and fractionation procedures for experimental purposes. (tile). Abubakar teaches methods include separation by chromatography (page 7, 2nd column-page 8). Abubakar teaches the use of filter paper made from cellulose including porous filter paper(page 8, (1) PC), glass wool filter (3)CC).
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to screen additional cells with other diseases phenotypes with plant or marine extracts using filtration or resins. The artisan would be motivated as Shoemaker specifically teaches the use of plant extracts to screen for cancer including the use of microarrays to identify new plants or compounds within a plant that provide for a physiological mechanism of action. The artisan would be motivated to use the preparation methods including filtration as Abubakar teaches these were known methods of preparing medicinal plant samples. The artisan would have a reasonable expectation of success as the artisan is merely using known methods and samples to screen for cellular responses including transcription.
Soul teaches, “use of animal models overcomes some of the limitations of human ex vivo OA culture models, potentially allowing more translatable research not only with modelling of pathology of the whole joint but also clinically-relevant pain outcomes.” (page 376, 1st column, bottom) Soul teaches, “This study has provided a resource for researchers to contextualise new data or explore existing publications. The OA genes can be used in tools to combine new differential expression datasets with the prior knowledge of OA joint damage-associated genes. This database provides researchers with means mine new targets for evidence of interactions with known OA genes and examine cross-species and cross-model gene expression dysregulation. Ultimately, we hope ongoing addition to and use of the database will improve understanding of the molecular pathophysiology of OA joint damage and lead to the development of disease modifying therapies for this currently intractable condition.”(page 382, bottom)
Yiman teaches, “The MIA-induced OA disease model in rats is a standardized model most frequently used to mimic the human OA.14 The model involves inoculation of MIA into a femorotibial joint pocket that induces pain responses in the ipsilateral limb accompanied by progressive cartilage degradation. Intraarticular injection of MIA disrupts chondrocyte glycolysis by inhibiting glyceraldehyde-3-phosphatase dehydrogenase and results in chondrocyte death, neovascularization, subchondral bone necrosis and collapse, as well as inflammation.”
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to test botanicals or natural extracts identified by the methods of Mu, Rasheed, Monagas in subjects with osteoarthritis including the use of controls such as placebos and/or reference treatments. The artisan would be motivated to determine if the botanical or extract produce the same effect in vivo as in vitro. The artisan would have a reasonable expectation of success as the art demonstrates in vivo and in vitro assays for gene expression with osteoarthritis supplements or botanicals were known.
With regards to claim 16, Soul teaches, “use of animal models overcomes some of the limitations of human ex vivo OA culture models, potentially allowing more translatable research not only with modelling of pathology of the whole joint but also clinically-relevant pain outcomes.” (page 376, 1st column, bottom) Soul teaches, “This study has provided a resource for researchers to contextualise new data or explore existing publications. The OA genes can be used in tools to combine new differential expression datasets with the prior knowledge of OA joint damage-associated genes. This database provides researchers with means mine new targets for evidence of interactions with known OA genes and examine cross-species and cross-model gene expression dysregulation. Ultimately, we hope ongoing addition to and use of the database will improve understanding of the molecular pathophysiology of OA joint damage and lead to the development of disease modifying therapies for this currently intractable condition.”(page 382, bottom
Response to Arguments
The response traverses the rejection in view of the amendment and declaration. This argument has been thoroughly reviewed but is not considered persuasive for the reasons of record with respect to declaration.
Summary
No claims are allowed.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Cope (Osteoarthritis and Cartilage 27 (2019) 230e239)
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/Steven Pohnert/Primary Examiner, Art Unit 1683
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