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 .
Elections/Restrictions
Applicant's election without traverse of the claims of Group II, claims 8-10 & 2-3 as amended, and the species election with traverse of PD-1 inhibitors claim 9 and with traverse of breast cancer in claim 10 in the reply filed on 10/31/2025 is acknowledged. Group I, claims 1 & 4-7, Group III, claims 11 & 12, Group IV, claim 13, and Group V, claims 14 & 15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. The traversal of the species elections is on the ground(s) that to be a permissible species election requirement there must be (1) a patentable difference between the species as claimed and (2) a serious search burden on the examiner if there is no restriction. Further, the traversal is on the grounds that, for example, the Patent Office is asserting that there must be a patentable difference between the species as claimed and such that prior art that discloses a PD-L1 inhibitor does not teach or render obvious a PD-1 inhibitor and so on and if this were not accurate than there is not a patentable difference between the species as claimed and the restriction is not permissible. In addition, the traversal is on the grounds that, for example, the Patent Office is asserting that there must be a patentable difference between the species as claimed and such that prior art that discloses breast cancer does not teach or render obvious bladder cancer and so on and that if this were not accurate then there is not a patentable difference between the species as claimed and the restriction is not permissible. This is not found persuasive because this is a national stage application filed under 35 U.S.C. 371. The standard for restriction in such an application is a lack of unity determination, which was set forth in the previous office action at paragraph 5 in which it was determined that the species lack unity of invention because they lack the same or corresponding feature since they are directed to structurally and functionally different therapy modalities and mechanisms (types of immune checkpoint inhibitors) and disease pathologies (types of cancer).
The requirement is still deemed proper and is therefore made FINAL.
A first office action on the merits of claims 2, 3, & 8-10 with the species elections of PD-1 inhibitors in claim 9 and of breast cancer in claim 10 is set forth herein and claims 1, 4-7, & 11-15 are withdrawn from consideration.
Information Disclosure Statement
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.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on pages 30 & 32. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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 2, 3, & 8-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The 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.
The claims require treating cancer in a subject diagnosed not to be in an immunosuppressive state through inferring Notch cellular signaling pathway activity based on expression levels of any three or more target genes and determining absence of activated Treg cells based on the inferred Notch cellular signaling pathway activity.
The claims are broadly drawn to inferring Notch cellular signaling pathway activity based on determined expression levels of three or more genes. The specification states that a Bayesian network computational mathematical model calculates mRNA levels of a selected, usually between 20 and 30, target genes of the pathway-associated transcription factor probability score for pathway activity (pg. 11 & 32 of the specification). The specification lists a set of target genes that it states can be used to “infer” Notch cellular signaling pathways (pg. 19 of the specification). However the specification does not teach how this list of genes is to be used in inferring Notch signaling pathway activity, nor does the specification provide any guidance on a particular model or algorithm for determining Notch signaling pathway activity using those genes.
In analyzing whether the written description requirement is met for a genus, it is first determined whether a representative number of species have been described by their complete structure. The specification of the instant application provides an example for quantitatively measuring the functional activity of PI3K, NFκB, TGFβ, JAK-STAT1/2, JAK-STAT3, and Notch signal transduction pathways on Affymetrix Human Genome U133 Plus 2.0 expression mircoarrays through a Bayesian network computational mathematical model (pg. 32 of the specification). The specification of the instant application also states that the activity of the FOXO transcription factor and of the NFκB, TGFβ, JAK-STAT1/2, JAK-STAT3, and Notch signaling pathways were measured in resting and activated states in samples from patients with breast cancer (pg. 34 of the specification). Finally, the specification of the instant application asserts that Notch pathway activity was significantly increased in blood samples from breast cancer patients compared to healthy individuals (pg. 35 of the specification), however, no guidance is given regarding levels of expression or a particular model or algorithm. Without this, or a clear definition as to which genes are or are not included in the claimed genus, the skilled artisan would be unable to determine which genes are encompassed by the claimed genus and would provide the functionality of diagnosing a subject to be in an immunosuppressed state versus those that are not. Additionally, the specification does not provide any guidance as to whether the list of genes recited could be used for any type of cancer, especially as the specification only provides examples with samples from breast cancer patients. Therefore, the recited list of genes is not representative of the claimed genus.
Next, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics, specific features, and functional attributes that would distinguish members of the claimed genus. In the instant application, the specification provides lists of target genes that is states are associated with different cellular signaling pathways. The specification of the instant application does not provide characteristics that would allow one to identify what particular genes from the lists would be used to infer Notch cellular signaling pathway activity and the functionality of diagnosing a subject to be in an immunosuppressed state in any type of cancer that would be encompassed by the breadth of the claims.
In the instant application, because of the lack of guidance regarding the particular levels of expression and particular model or algorithm required to infer Notch cellular signaling pathway activity and the lack of guidance of inferring Notch cellular signaling pathway activities in a representative number of cancer types, one of skill in the art cannot envision the detailed structure of the nucleic acids and model or algorithm encompassed by the claimed methods, regardless of the complexity or simplicity of the method of isolation or use. Adequate written description requires more than a mere statement that such nucleic acids and model or algorithm are part of the inventions and reference to a potential method of treating cancer through diagnosing a subject to not be in an immunosuppressed state.
In conclusion, the limited information provided regarding treating any cancer through diagnosing a subject to not be in an immunosuppressed state of the claimed methods is not deemed to reasonably convey to one skilled in the art that the applicant is in possession of the broadly claimed method because the claims encompass a large genus of treating cancer through inferring cellular signaling pathway activity based on expression levels of any three or more target genes which are not described in the specification.
Thus, having considered the breadth of claims and the provisions of the specification, it is concluded that the specification does not provide adequate written description for the claims.
Claims 2, 3, & 8-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
There are many factors to be considered when determining whether there is sufficient evidence to support determination that a disclosure does not satisfy the enablement requirements and whether any necessary experimentation is undue. These factors have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The nature of the invention and the breadth of the claims:
The claims are broadly drawn to a method of treating cancer in a subject diagnosed not to be in an immunosuppressive state with an immune checkpoint inhibitor in which receiving a diagnosis that the subject is not in an immunosuppressed state comprises inferring Notch cellular signaling pathway activity based on determined expression levels of three or more target genes in a blood sample obtained from a subject, determining the absence of activated Treg cells based on the inferred Notch cellular signaling pathway activity, and diagnosing the subject to not be in an immunosuppressed state based on the absence of activated Treg cells.
The amount of direction or guidance and Presence/absence of working examples:
The specification asserts quantitatively measuring functional activity of PI3K, NFκB, TGFβ, JAK-STAT1/2, JAK-STAT3, and Notch signal transduction pathways on Affymetrix Human Genome U133 Plus 2.0 expression mircoarrays through a Bayesian network computational mathematical model which calculates mRNA levels of a selected, usually between 20 and 30, target genes of the pathway-associated transcription factor probability score for pathway activity (pg. 11 & 32 of the specification). The specification also lists a set of target genes that it states can be used to “infer” Notch cellular signaling pathways (pg. 19 of the specification). Further, the specification states that depending on the value of the computational mathematical model, it can be used to relate gene expression levels to a cellular signaling pathway in which a value of 0 indicated no pathway activity and a value of 100 is theoretical maximum pathway activity (pg. 11 of the specification).
The specification does not provide any teaching or guidance as to which target genes expression levels are measured to infer the Notch cellular signaling pathway activity of a sample or what type of expression levels are measured or what the relationship is between the type of target gene expression levels that are measured and inferring an increase or decrease in Notch cellular signaling pathway activity. In addition, while the specification states that the numerical value for the pathway activity in a sample be compared to a reference sample, in which the reference sample can be from a tumor sample known not to be in an immunosuppressed state, to determine whether the pathway activity in the sample is higher or lower than the reference (pg. 11-12 of the specification), the specification does not provide any guidance to if the expression levels of the same particular three or more target genes must be used to infer the Notch cellular signaling pathway activity in the reference compared to the subjects sample. In addition, the specification does not provide any guidance on how to determine a tumor sample is known not to be in an immunosuppressed state or what values of cellular signaling pathway activity are determined to be high (as the specification states that Notch cellular signaling pathway activity was determined to be high in activated Treg cells and therefore could be set as a baseline reference value) when determining a frame of reference to compare to.
The state of the prior art and the predictability or unpredictability of the art:
The claims are directed treating cancer in a subject through diagnosing a subject not to be in an immunosuppressed state based on the determined absence of activated Treg cells based on the inferred Notch cellular signaling pathway activity based on the determined expression levels of three or more target genes. However, there is no teaching or guidance in either the specification or the art as to the methods of treating cancer in a subject as broadly claimed. For example, the prior art, Aster (Aster, Pear, & Blacklow; Annual Review of Pathology: Mechanisms of Disease, Vol. 12, pages 245-275, December 2016) teaches that there are various distinct patterns of Notch gene mutation in various human cancers, including distinct patterns observed in breast cancer, lymphomas, lung cancers, etc. (pg. 253 1st full paragraph lines 1-18; pg. 253-255 paragraph bridging pg. 253 & pg. 255 lines 1-17; pg. 255 1st full paragraph lines 1-11). Further, Aster teaches that distinct patterns of Notch gene mutation in various cancer types can lead to increased or decreased levels of target genes (pg. 253-255 paragraph bridging pg. 253 & pg. 255 lines 1-17; pg. 255-256 paragraph bridging pg. 255 & pg. 256 lines 1-7). In addition, Zhou (Zhou et al.; Signal Transduction and Targeted Therapy, Vol. 7, pages 1-33, March 2022) teaches that the pattern of Notch activation varied in different cancer types, for example through activation of Notch signaling pathway by upstream or downstream tumor-associated signaling factors such as MYC or P53, and further in which different genes are expressed in Notch signaling in different cancers (pg. 10 -11 paragraph bridging pg. 10 & pg. 11 lines 1-13. For example, Zhou teaches that MYC expression may be induced by Notch signaling in hematological cancers, JAG1 and JAG2 is correlated with Notch signaling in ovarian cancer, and expression of lncRNA and TUG1 are induced by Notch signaling in glioma (pg. 11 column 1 1st full paragraph lines 12-15; pg. 13 column 1 2nd full paragraph lines 4-10; pg. 13 column 2 2nd full paragraph lines 10-12). Finally, Yoshihara (Yoshihara & Takahashi; Frontiers in Cell and Developmental Biology, Vol. 11, pages 1-6, July 2023) teaches that Notch signaling downstream targets are induced by multiple signaling pathways leading to complexity when determining the patterning mechanisms of Notch signaling (pg. 1 1st full paragraph lines 6-7; pg. 2-3 paragraph bridging pg. 2 & pg. 3 lines 22-27; pg. 3 paragraph bridging column 1 & 2 lines 14-16; pg. 4 column 1 1st full paragraph lines 1-5; pg. 4 column 2 1st full paragraph lines 12-17).
The level of skill in the art:
The level of skill in the art is deemed to be high.
The quantity of experimentation necessary:
To practice the invention as broadly claimed, the skilled artisan would be required to perform a large study of cases and controls to determine the experimental parameters required to predictably diagnose a subject to not be in an immunosuppressed state based on the determined absence of activated Treg cells based on the inferred Notch cellular signaling pathway activity based on the determined expression levels of three or more target genes. The specification does not provide guidance as to which target genes expression levels are measured to infer the Notch cellular signaling pathway activity of a sample, what type of expression levels are measured, what the relationship is between the type of target gene expression levels that are measured and inferring an increase or decrease in Notch cellular signaling pathway activity, or what particular model or algorithm is used to determine cellular signaling pathway activity. This analysis appears to be replete with trial and error experimentation given the conflicting guidance in the art as noted above. Given the lack of guidance in specification, the skilled artisan would be required to establish the assay, conditions, and parameters requiring a large amount of inventive effort with each step.
Thus given the broad claims in an art whose nature is identified as unpredictable, the large quantity of research required to define these unpredictable variables, the lack of guidance provided in the specification, and the absence of a working example balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
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 2, 3, & 8-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 2, the recitation of “inferring Notch cellular signaling pathway activity based on determined expression levels of three of more target genes” in lines 2-3 of the claim is unclear. It is unclear what the relationship is between Notch cellular signaling pathway activity and the expression levels of three target genes. Does increased or decreased expression of the three target genes indicate a particular Notch cellular signaling pathway activity? How does the expression of target genes relate back to Notch cellular signaling pathway activity and what type of activity is inferred and how is this activity measured?
Regarding claim 3, the recitation of “the JAK-STAT3 cellular signaling pathway is inferred in the cells of the blood sample based on determined expression levels of three of more target genes” in lines 2-3 of the claim is unclear. It is unclear what the relationship is between JAK-STAT3 cellular signaling pathway and the expression levels of three target genes. Does increased or decreased expression of the three target genes indicate a JAK-STAT3 cellular signaling pathway? How does the expression of target genes relate back to JAK-STAT3 cellular signaling pathway? In addition, the claim recites the limitation “the JAK-STAT3 cellular signaling pathway” in lines 2 of the claim and there is insufficient antecedent basis for this limitation in the claim. In addition, the recitation of “three or more target genes” in lines 3 of the claim followed by the recitation of “is determined based on the combined inferred Notch and JAK-STAT3 cellular signaling pathway activities” in lines 4-5 of the claim is unclear. It is unclear is the combined inferred Notch and JAK-STAT3 cellular signaling pathway activities are based on the same three or more target genes expression or if the expression of three or more target genes are used to infer the activity of the Notch cellular signaling pathway activity and a different three or more target genes are used to infer the activity of the JAK-STAT3 cellular signaling pathway activity (i.e., at least 6 or more gene expression is used to inferred the combined cellular signaling pathway activities). If the former is true, how does the expression levels of the same three or more target genes infer a combined cellular signaling pathway activities?
Regarding claim 8, the recitation of “inferring Notch cellular signaling pathway activity based on determined expression levels of three of more target genes” in lines 7-8 of the claim is unclear. It is unclear what the relationship is between Notch cellular signaling pathway activity and the expression levels of three target genes. Does increased or decreased expression of the three target genes indicate a particular Notch cellular signaling pathway activity? How does the expression of target genes relate back to Notch cellular signaling pathway activity and what type of activity is inferred and how is this type of activity measured? In addition, the recitation of “determining the absence of activated Treg cells in the blood sample based on the inferred Notch cellular signaling pathway activity” in lines 10-11 of the claim followed by the recitation of “diagnosing the subject to not be in an immunosuppressed state based on the determined absence of activated Treg cells in the blood sample” in lines 12-13 of the claim is unclear. It is unclear what the relationship between inferring Notch cellular signaling pathway activity and diagnosing the subject to not be in an immunosuppressed state. Does the presence, increased, or decreased Notch cellular signaling pathway activity determine the absence of activated Treg cells and therefore the subject to not be in an immunosuppressed state? Finally, the claim recites the limitation “the checkpoint inhibitor” in line 14 of the claim and there is insufficient antecedent basis for this limitation in the claim and it is unclear if “the checkpoint inhibitor” is referring back to “an immune checkpoint inhibitor” in lines 3 of the claim or is referring to a different checkpoint inhibitor.
Regarding claim 9, the recitation of “LAG3 inhibitors, TIM-3 inhibitors, TIGIT inhibitors and VISTA inhibitors” in lines 3-4 of the claim is unclear if TIGIT and VISTA inhibitors are a part of the same group of immune checkpoint inhibitors, or if this is the result of a typographical error and should read “LAG3 inhibitors, TIM-3 inhibitors, TIGIT inhibitors, and VISTA inhibitors”. In addition, the recitation of “MTIG7192A (TIGIT), RG6058 (TIGIT), bms-986207(TIGIT) and JNJ-61610588 (VISTA)” in lines 8-9 of the claim is unclear if bms-986207(TIGIT) and JNJ-61610588 (VISTA) are a part of the same group of immune checkpoint inhibitors, or if this is the result of a typographical error and should read “MTIG7192A (TIGIT), RG6058 (TIGIT), bms-986207(TIGIT), and JNJ-61610588 (VISTA)”.
Regarding claim 10, the recitation of “skin cancer, stomach cancer, rectal cancer or a solid tumor” in line 5 of the claim is unclear if rectal cancer and a solid tumor are a part of the same group of cancers, or if this is the result of a typographical error and should read “skin cancer, stomach cancer, rectal cancer, or a solid tumor”.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 2, 3, 8, & 10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation/law of nature and an abstract idea without significantly more. This 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 for the reasons set forth below.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106. The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, 561 U.S. 593, 601 (June 28, 2010) and Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014). See also Myriad v Ambry, CAFC 2014-1361, -1366, December 17, 2014. The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 71 (2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Dia-mond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. at 601 (2010).
Claims Analysis:
As set forth in MPEP 2106, the claims have been analyzed to determine whether they are directed to one of the four statutory categories (STEP 1).
The instant claims are directed to methods and therefore are directed to one of the four statutory categories of invention.
The claims are then analyzed to determine if they recite a judicial exception (JE) (STEP 2A, prong 1) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)].
The claimed invention recites a method of treating cancer in a subject diagnosed to not be in an immunosuppressed state through receiving a diagnosis that the subject is not in an immunosuppressed state through inferring Notch cellular signaling pathway activity based on determined expression levels of three or more target genes, determining the absence of activated Treg cells, diagnosing the subject to not be in an immunosuppressed state based on the determined absence of activated Treg cells, and administering a checkpoint inhibitor. This recitation is a natural correlation between diagnosed to not be in an immunosuppressed state and expression levels of three or more target genes. With regard to the natural correlation, as in Mayo, the relationship is itself a natural process that exists apart from any human action. The claimed invention also recites receiving, inferring, and determining which are a recitation of an abstract ideas because it encompasses conclusions and determinations which can occur entirely within the mind. It is therefore determined that the claims are directed to judicial exceptions.
The claims are then analyzed to determine whether they recite an element or step that integrates the JE into a practical application (STEP 2A, prong 2) [Vanda Pharmaceuticals Inc., v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018)].
The claims recite steps of receiving a diagnosis that the subject is not in an immunosuppressed state through inferring Notch cellular signaling pathway activity based on determined expression levels of three or more target genes, determining the absence of activated Treg cells based on the inferred Notch cellular signaling pathway activity, diagnosing the subject to not be in an immunosuppressed state based on the determined absence of activated Treg cells, and administering a checkpoint inhibitor, however this does not integrate the JE into a practical application because it is a mere data gathering step to use the correlation and does not add a meaningful limitation to the method.
Although the claims recite “administering the checkpoint inhibitor” to the patient, this step is conditional as it is “based on” determining an absence of activated Treg cells in a blood sample based on inferred Notch cellular signaling pathway activity which is based on the expression levels of three or more target genes in the blood sample. Accordingly, these generally recited elements are considered nothing more than instructions to apply the law of nature because no particular conditions are required by the step of detecting gene expression or inferring Notch cellular signaling pathway activity and the absence of activated Treg cells. As such, the “administering” step is merely a generalized “treat” limitation with no particularity that integrates the judicial exception into a practical application. The Supreme Court does acknowledge that it is possible to transform an unpatentable law of nature, but one must do more than simply state the law of nature while adding the words "apply it.” CLS BankInt’l, 134 S.Ct. at 2358; Prometheus, 132 S. Cl, at 1294.
In the absence of steps or elements that integrate the JE into a practical application, the additional elements/steps are considered to determine whether they add significantly more to the JE either individually or as an ordered combination, to “’transform the nature of the claim’ into a patent eligible application” [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)] (STEP 2B).
In the instant situation, the steps of receiving a diagnosis that the subject is not in an immunosuppressed state are generally recited and do not provide any particular reagents that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. This step is not only a mere data gathering step, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)). Applicant is reminded that in Mayo, the Court found that “[i]f a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Further "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law”. Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at ___ (slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ . . . adding ‘insignificant post-solution activity’” (quoting Diehr, supra, at 191–192)). The Court also summarized their holding by stating “[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.” Therefore these limitations/steps do not “‘transform the nature of the claim’ into a patent-eligible application.’” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
When viewed as an ordered combination, the claimed limitations are directed to nothing more than the determination that a natural correlation/phenomena exists. Any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.
Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 2, 3, & 8-10 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Van Doorn (WO 2019/068623 A1, published April 2019), as cited in the IDS dated 03/23/2023.
Regarding claim 2, Van Doorn teaches determining the functional status of at least one immune cell type, including in Treg cells (T cells) characterized as a resting status (absence of activated Treg cells) by a lower Notch pathway (inferring Notch cellular signaling pathway activity) than a suppressive status in a blood sample from the subject (pg. 6 lines 9-19; pg. 10 lines 5-7; pg. 11 lines 8-17; pg. 69-70 claim 8 lines 1-4 & 32-34; pg. 70 claim 9 lines 1-12; pg. 70-71 claim 10 lines 1-12). Van Doorn also teaches that the activity of a signaling pathway, including Notch cellular signaling pathway activity, can be assessed through expression in target genes and preferably by receiving the expression levels of three or more target genes of the signaling pathway (inferring Notch cellular signaling pathway activity based on determined expression levels of three or more target genes in a blood sample) (pg. 8 lines 1-9; pg. 18 lines 1-3 & 24-31).
Regarding claim 3, Van Doorn teaches that the Treg cells can be also characterized by determining the pathway activity of two or more signaling pathways, including Notch signaling pathway and JAK-STAT3 signaling pathway, to determine activated supportive state (presence of Treg cells is determined based on the combination of inferred Notch and JAK-STAT3 cellular signaling pathway activities) in a blood sample from the subject (pg. 6 lines 3-9; pg. 10 lines 5-7; pg. 14 lines 1-5). Van Doorn also teaches that the activity of a signaling pathway, including Notch cellular signaling pathway activity and JAK-STAT3 cellular signaling pathway activity, can be assessed through expression in target genes and preferably by receiving the expression levels of three or more target genes of the signaling pathway (inferring JAK-STAT3 cellular signaling pathway activity based on determined expression levels of three or more target genes in a blood sample) (pg. 8 lines 1-9; pg. 17 lines 20-24; pg. 18 lines 1-3 & 24-31).
Regarding claim 8, Van Doorn teaches a method for determining immune system activity of a subject through determining the functional status of at least one immune cell type including in Treg cells characterized as a resting status (absence of activated Treg cells) by a lower Notch pathway (inferring Notch cellular signaling pathway activity) than a suppressive status (diagnosing the subject to be in an immunosuppressive state based on the determined absence of Treg cells in a sample based on the inferred Notch cellular signaling pathway activity) (pg. 6 lines 9-19; pg. 11 lines 8-17; pg. 69-70 claim 8 lines 1-4 & 32-34; pg. 70 claim 9 lines 1-12; pg. 70-71 claim 10 lines 1-12). Van Doorn also teaches that the activity of a signaling pathway, including Notch cellular signaling pathway activity, can be assessed through expression in target genes and preferably by receiving the expression levels of three or more target genes of the signaling pathway (inferring Notch cellular signaling pathway activity based on determined expression levels of three or more target genes in a sample) (pg. 8 lines 1-9; pg. 18 lines 1-3 & 24-31). Van Doorn also teaches that measuring the pathway activity in immune cell types, including Treg cells, and assessing the activity or immune suppressed status (diagnosing as in an immunosuppressed state) can be used to assess therapy response, adjust/optimize dosage of therapy, and monitor immune response state in any disease, including cancer (treating cancer in a subject) including treatment with checkpoint inhibitor drugs (administering the checkpoint inhibitor) (pg. 3 lines 4-16 & 20-31; pg. 10 lines 11-24). In addition, Van Doorn teaches that the sample can be a blood sample taken from the subject (pg. 10 lines 5-7).
Regarding claim 9, Van Doorn teaches the immune checkpoint inhibitor drug can be PD1 inhibitors (pg. 3 lines 27-31).
Regarding claim 10, Van Doorn teaches measuring an immunosuppressive state in breast cancer samples (pg. 39 lines 22-32; pg. 40 line 1).
Conclusion
Claims 2, 3, & 8-10 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY C BUCHANAN whose telephone number is (703)756-1315. The examiner can normally be reached Monday-Friday 8:00am-5:00pm ET.
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/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/ Primary Examiner, Art Unit 1682