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 .
Claim Summary
Claims 1, 2, and 7-16 have been amended. Claims 3, 17, and 19 have been canceled. Claims 21-23 have been added. Claims 1, 2, 4-16, 18, and 20-23 are pending. Claims 1, 2, 4-16, 18, and 20-23 are under examination and discussed in this Office action.
Response to Amendment
The amendment filed April 10th, 2025 is acknowledged. Regarding the Office Action mailed January 10th, 2025:
The rejection set forth under 35 U.S.C. 112(b) is withdrawn in view of the amendments.
The rejection set forth under 35 U.S.C. 102 is withdrawn in view of the amendments.
The rejection set forth under 35 U.S.C. 103 is withdrawn in view of the amendments.
New grounds of rejection are set forth below, as necessitated by the amendments.
Claim Rejections - 35 USC § 112(a) – NEW – Necessitated by Amendment
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 1, 2, 4-15, 18, and 20-23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. This is a scope of enablement rejection because the specification, while being enabling for a method for determining a subject's gene expression inflammatory age (GE iAge), comprising the steps of: (a) obtaining a sample from a subject; (b) measuring the expression of fifteen genes in a cell in the sample from the subject to obtain a mean gene expression signal consisting of a GBP5, a MMP9, a SIGLEC5, a S100P, an OLFM1, a CISH, a MT1A, a CHURC1, an IGLL1, a RPLP0, a SLC16A10, a FCER1A, a CD248, a DDX3Y, and a MAN1A1; (c) normalizing the mean gene expression signal by multiplying it by a regression coefficient for each gene; and (d) adding the resultant number to calculate the subject's GE iAge, this does not reasonably provide enablement for a method for determining a subject's gene expression inflammatory age (GE iAge), comprising the steps of: (a) obtaining a sample from a subject; (b) measuring the expression of three or more genes in a cell in the sample from the subject to obtain a mean gene expression signal wherein three or more genes are selected from a group consisting of a GBP5, a MMP9, a SIGLEC5, a S100P, an OLFM1, a CISH, a MT1A, a CHURC1, an IGLL1, a RPLP0, a SLC16A10, a FCER1A, a CD248, a DDX3Y, and a MAN1A1; (c) normalizing the mean gene expression signal by multiplying it by a regression coefficient for each gene; and (d) adding the resultant number to calculate the subject's GE iAge as embraced by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” See MPEP § 2164. These factors include, but are not limited to: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The office has analyzed the specification in direct accordance to the factors outlines in In re Wands. MPEP 2164.04 states: “[W]hile the analysis and conclusion of a lack of enablement are based on factors discussed in MPEP 2164.01(a) and the evidence as whole, it is not necessary to discuss each factor in written enablement rejection.” These factors will be analyzed, in turn, to demonstrate that one of ordinary skill in the art would have had to perform “undue experimentation” to make and/or use the invention and therefore, applicant’s claims are not enabled.
(A) With respect to the breadth of the claims: Claim 1 as currently drafted encompasses a method for determining a subject’s gene expression inflammatory age (GE iAge) comprising obtaining a sample, measuring gene expression of 3 or more genes from the 15 listed in claim 1, normalizing the mean expression by multiplying it by a regression coefficient for each gene, and adding the resultant number to calculate the subject’s GE iAge. The claim is overly broad because it requires only three of fifteen biomarkers, which results in thousands of different combinations of markers, none of which have appear to have support for determining a GE iAge. Consequently, the breadth of the claim is expansive. Claims 2, 4-15, 18, and 20-23 encompass the same breadth as claim 1 since they do not limit the measured genes to all 15 in the list of claim 1, and in fact claims 6-16 and 21 make the number of combinations increase by requiring progressively more genes.
(B) The nature of the invention: The invention is in the field of determining a gene expression inflammatory age via the expression of biomarkers.
(C), (D), (E) With respect to the state of the prior art, the level of one of ordinary skill and predictability of the art: Mayeux (Biomarkers: potential uses and limitations, NeuroRX, April 2004, 2, 182-188) teaches that while biomarkers provide a dynamic and powerful approach to understanding a spectrum of diseases, variability is a major concern in biomarkers (Summary). Biomarkers are subject to critical timing regarding sample collection, storage conditions, and adequate laboratory handling (Table 2). Further, normal ranges are often difficult to establish, given interindividual variability, tissue localization, reliability of the biomarker measurements, and persistence of the biomarker (Pages 187-188). This would make comparison to establish disease or select treatment highly unpredictable.
This is especially true in inflammaging, which was only identified as a body process two decades ago (see Fulop, Immunology of Aging: the Birth of Inflammaging, Clinical Reviews in Allergy and Immunology, September 2021, 64, 109-122; see abstract). According to Fulop, there are many different definitions of aging, and none of them capture its complexity since they do not use the integration of complex systems (Page 109). Even the current definition of the hallmarks of aging seems to be a sort of catalogue of pathways without really defining the basic interactions between these hallmarks and how they interact, which would influence the whole complex process (Page 109).
According to Liu (Biomarkers of chronic inflammation in disease development and prevention: challenges and opportunities, Nature Immunology, October 2017, 18, 1175-1180), reports of inconsistent results from biomarker-discovery research have been due in part to the lack of robust biomarker validation, lack of quality control and insufficient causal evidence linking chronic inflammation biomarkers to disease development (Page 1179). Many population-based studies have provided data on the association of inflammatory markers with diseases (population studies mentioned during the workshop are in Box 2; Page 1179). However, as with biomarker identification in other research areas, such studies are hampered by the lack of reliable assays, scarce biospecimens and limited longitudinal data from the same subject (Page 1179). These challenges make the translation of biomarker discovery to the clinic difficult (Page 1179).
Given this unpredictability in the field, one of skill in the art would not be able to engage in routine experimentation to determine which biomarker combinations to use out of the thousands of possible combinations presented in the claims for determining GE iAge. In fact, it would take an enormous amount of undue experimentation to test the combinations presented by the claims. Therefore, methods for determining GE iAge comprising any combination of the claimed genes other than all 15 as described in the specification is highly unpredictable.
The invention is drawn to biological molecules, and is therefore in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). The level of skill in the art is therefore deemed to be high.
(F), (G) With respect to the amount of direction and working examples provided by the applicant: The Applicant has provided one description directed towards using all the genes of claim 1. As presented in the specification, “To derive gene expression inflammatory age (GE iAge), the mean gene expression signal can be normalized and used for multiple regression analysis, which is computed using the following regression coefficients: GBP5: 1.3452, MMP9: 0.6083, SIGLEC5: 0.5419, S100P: 0.4408, OLFM1: 0.4155, CISH: 0.2270, MT1A: 0.1978, CHURC1: -0.1308, IGLL1: -0.2250, RPLP0: -0.2861, SLC16A10: -0.4742, FCER1A: -0.6154, CD248: -0.6580, DDX3Y: -0.6937, MAN1A1: -0.7070. The gene expression signal can be multiplied by the regression coefficient for the gene, and these numbers can be all added together to give the GE iAge of the subject.” (Page 18, paragraph [074]). This implies that the expression of all 15 genes would be needed. The working example provided later in the disclosure, while titled “Gene Expression iAge”, does not appear to relate to GE iAge, but instead another metric called iAge (Page 77, paragraphs [0235]-[0236]).
The applicants have not provided direction or examples comprising using between 3 and 14 of the claimed genes to determine GE iAge, as covered in claims 1, 5-15, and 21.
(H) Undue experimentation would be required to practice the invention as claimed due to the amount of experimentation necessary because of the expansive breadth of the claims, the state of the prior art and its high unpredictability, and the limited amount of guidance in the form of varied working examples in the specification. A skilled artisan recognizes that using 15 specific genes for determining a GE iAge is distinct from using any three or more genes from a selected list for determining a GE iAge. A skilled artisan would know that using any three or more genes from a selected list would require multiple experiments for each possible group of three or more, using large cohorts of all possible “subjects” as claimed, which include a variety of species (human, dog, cat, bird, etc.). Thus, applicability of the claimed method to any 3 or more genes up to 14 as embraced by the claim remains unpredictable, requiring undue experimentation.
MPEP §2164.01(a), 4th paragraph, provides that, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC), states that, “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable,” citing Brenner v. Manson, 383 U.S. 519, 536 (1966) (stating, in the context of the utility requirement, that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion”). The Genentech decision continued, “tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Id. at p. 1005.
After applying the Wands factors and analysis to claims 1, 2, 4-15, 18, and 20-23, in view of the applicant’s entire disclosure, and considering the In re Wright, In re Fisher and Genentech decisions discussed above, it is concluded that the practice of the full scope of the invention as claimed would not be enabled by the written disclosure. Therefore, claims 1, 2, 4-15, 18, and 20-23 are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to practice the claimed invention to it the full scope embraced by the claims. However, claim 16 appears to claim measuring expression of all 15 genes, is enabled based on the specification.
Written Description
Claims 1, 2, 4-15, 18, and 20-23 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.
Issues of New Matter in the claims
The content of claims 22 and 23 introduces new matter that is not adequately described in the originally filed specification, claims, drawings, or abstract. In regards to amendments to the claims, MPEP 2163.06(I) states “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981)”.
Claim 22 recites the limitation “The method of claim 1, wherein the calculated GE iAge correlates to an immunological age”. The Applicant cites paragraphs [008] and [074], as well as Table 1, for support of the added claim. However, in paragraphs [008] and [074], GE iAge is only described as a gene expression inflammatory age. There is no indication it is an immunological age, nor that it is correlated with an immunological age. Table 1 does not describe GE iAge or immunological age at all, but instead inflammatory age (iAge) ranges. iAge appears to be a different metric based on measurements of proteins that are different from genes that are claimed for determining GE iAge (Page 13, paragraph [057]). Beyond the Applicants citations, the Examiner cannot find a description in the specification that adequately supports the correlation of GE iAge to an immunological age.
Claim 23 recites the limitation “The method of claim 22, further comprising:(e) comparing the immunological age to the subject's chronological age, wherein when the subject's chronological age is equal to or less than the immunological age, the subject is classified as being capable of responding to an immunotherapy and when the subject's chronological age is greater than the immunological age, the subject is classified as a non-responder to an immunotherapy.” Like for claim 22, the Applicant cites paragraphs [008] and [074], as well as Table 1, for support of the added claim. However, in paragraphs [008] and [074], there is no description of comparisons of immunological age to chronological age. These paragraphs deal with describing GE iAge, a gene expression inflammatory age, with no indication that it is an immunological age. Table 1 does not describe immunological age or GE iAge at all, but instead iAge ranges (Page 13, paragraph [057]; Table 1). There is no indication that iAge is immunological age, since it is described as inflammatory age (Page 13, paragraph [057]), and also no indication that it is the same as GE iAge. Therefore, although Table 1 compares iAge to chronological age, this does not support comparing immunological age to a subject’s chronological age. Further description regarding this comparison can be found in paragraph [016]; however, the comparison is still using an inflammatory age, rather than an immunological age, and the comparison is made to patients of similar chronological age. There is no indication of a direct comparison between the subject’s immunological age and their chronological age. Due to the lack of description regarding the comparison, the rest of the claim regarding response to immunotherapy also lacks description.
In summary, claims 22 and 23 are rejected for introducing new matter not originally filed in the specification, claims, drawings, or abstract.
Issues of Inadequate Description of the claims
In making a determination of whether the application complies with the written description requirement under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is claiming and what Applicant has possession of. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V, v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was “ready for patenting” such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991). See MPEP § 2163.
Claim 1 recites the limitation “A method for determining a subject's gene expression inflammatory age (GE iAge), comprising the steps of: (a) obtaining a sample from a subject; (b) measuring the expression of three or more genes in a cell in the sample from the subject to obtain a mean gene expression signal wherein three or more genes are selected from a group consisting of a GBP5, a MMP9, a SIGLEC5, a S100P, an OLFM1, a CISH, a MT1A, a CHURC1, an IGLL1, a RPLP0, a SLC16A10, a FCER1A, a CD248, a DDX3Y, and a MAN1A1; (c) normalizing the mean gene expression signal by multiplying it by a regression coefficient for each gene; and (d) adding the resultant number to calculate the subject's GE iAge.” The claim as written embraces a method wherein the gene expression signal of three or more genes is used to determine a GE iAge. However, the specification does not provide a method by which to determine this GE iAge using expression of just three of the listed genes. In fact, the specification does not appear to provide a method by which to determine GE iAge with any less than all 15 of the claimed list of genes. As presented in the specification, “To derive gene expression inflammatory age (GE iAge), the mean gene expression signal can be normalized and used for multiple regression analysis, which is computed using the following regression coefficients: GBP5: 1.3452, MMP9: 0.6083, SIGLEC5: 0.5419, S100P: 0.4408, OLFM1: 0.4155, CISH: 0.2270, MT1A: 0.1978, CHURC1: -0.1308, IGLL1: -0.2250, RPLP0: -0.2861, SLC16A10: -0.4742, FCER1A: -0.6154, CD248: -0.6580, DDX3Y: -0.6937, MAN1A1: -0.7070. The gene expression signal can be multiplied by the regression coefficient for the gene, and these numbers can be all added together to give the GE iAge of the subject.” (Page 18, paragraph [074]). This does not appear to provide support for using less than all 15 of the described genes for the claimed calculations and instead implies that the expression of all 15 genes would be needed. The working example provided later in the disclosure, while titled “Gene Expression iAge”, does not appear to relate to GE iAge, but instead another metric called iAge (Page 77, paragraphs [0235]-[0236]). Based on the specification, the Applicant does not have possession of the method as claimed. Claims 2, 4-15, 18, and 20-23 do not further present possession of the method as claimed in claim 1 and are also rejected here. It is also noted that claims 6-15 and 21 suffer from the same issue of claiming less than 15 of the claimed genes, but claim 16 appears to claim measuring expression of all 15 genes, which does have support based on the specification.
Claim Rejections - 35 USC § 101 – NEW – Necessitated by Amendment
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 1, 2, 4-16, 18, and 20-23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon and abstract ideas without significantly more. While the claim(s) is/are directed to a process, and therefore meet step 1 of the subject matter eligibility test (see MPEP 2106.03), the claim(s) recite the natural correlation between gene expression and gene expression inflammatory age, the mathematical concepts of multiplication and addition, and also the mental process of comparing. The natural correlation between gene expression and gene expression inflammatory age is a natural phenomenon because it describes a consequence of natural processes in the human body (e.g. a change in gene expression during the process of aging). The mathematical concepts are abstract ideas as set forth in MPEP 2106.04(a). The mental process is an abstract idea as set forth in MPEP 2106.04(a).
Step 2A of the subject matter eligibility test requires a two-pronged analysis. Prong One asks: does the claim recite an abstract idea, law of nature or natural phenomenon? As discussed in MPEP 2106.04(II)(A)(1), the meaning of “recites” is “set forth” or “describes”. That is, a claim recites a judicial exception when the judicial exception is “set forth” or “described” in the claim. In the instant case, the claims describe a natural phenomenon and abstract ideas: the natural correlation between gene expression and gene expression inflammatory age, mathematical concepts of multiplication and addition, and the mental process of comparing.
Prong Two of the analysis under step 2A asks: does the claim recite additional elements that integrate the judicial exception into a practical application of the judicial exception? As discussed in MPEP 2106.04(II)(A)(2), “Because a judicial exception is not eligible subject matter, Bilski, 561 U.S. at 601, 95 USPQ2d at 1005-06 (quoting Chakrabarty, 447 U.S. at 309, 206 USPQ at 197 (1980)), if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception, that is insufficient to integrate the judicial exception into a practical application. See, e.g., RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017) ("Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract"); Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016) (eligibility "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself."). For a claim reciting a judicial exception to be eligible, the additional elements (if any) in the claim must "transform the nature of the claim" into a patent-eligible application of the judicial exception, Alice Corp., 573 U.S. at 217, 110 USPQ2d at 1981, either at Prong Two or in Step 2B.” The considerations to be used are set forth at MPEP 2106.05(a) through (h). Turning to those sections of the MPEP:
MPEP 2106.05(a) has to do with improvements to the functioning of a computer or to any other technology or technical field. The claims at issue do not improve the functioning of a computer or other technology. While the instant claims recite steps of determining a gene expression inflammatory age (GE iAge) by samples, which can be blood or serum; measuring expression of 3 or more of a list of 15 genes, with later steps encompassing measuring from between 4 to 15 genes; normalizing the mean gene expression; measuring via a multiplex assay and PCR; measuring cholesterol, gender, or BMI; correlating the GE iAge to an immunological age; and comparing the immunological age to a subject’s chronological age to determine if a subject is capable of responding to immunotherapy, the claims do not improve upon techniques for measuring gene expression, PCR, or comparison of controls to test samples. The claims merely use existing methods for these steps. Note that MPEP 2106.05(a) indicates that “[u]sing well-known standard laboratory techniques to detect enzyme levels in a bodily sample” is an example that the courts have indicated may not be sufficient to show an improvement to technology.
MPEP 2106.05(b) has to do with whether the claims involve the use of a particular machine. In this case, the claims do not involve the use of a particular machine. While the instant claims recite steps of determining a gene expression inflammatory age (GE iAge) by samples, which can be blood or serum; measuring expression of 3 or more of a list of 15 genes, with later steps encompassing measuring from between 4 to 15 genes; normalizing the mean gene expression; measuring via a multiplex assay and PCR; measuring cholesterol, gender, or BMI; correlating the GE iAge to an immunological age; and comparing the immunological age to a subject’s chronological age to determine if a subject is capable of responding to immunotherapy, no particular machines are required by the claim. Even if some conventional machine were recited in the claims, like a specific brand of PCR machine, further considerations such as the particularity or generality of the recited machine must be taken into account, as well as whether the involvement of the machine is merely extra-solution activity. MPEP 2106.05(g) describes “extra-solution activity”, noting that “[d]etermining the level of a biomarker in blood” is an example of “mere data gathering” which the courts have found to be insignificant extra-solution activity.
MPEP 2106.05(c) has to do with whether the claims involve a particular transformation. Here, none of the limitations of the claims involve a particular transformation. For example, measurement of expression of a gene does not turn that gene into something else.
MPEP 2106.05(e) has to do with “other meaningful limitations”. The additional limitations imposed upon the natural correlation between gene expression and gene expression inflammatory age, mathematical concepts of multiplication and addition, and the mental process of comparing in the instant case have to do with specifically collecting blood or serum samples, measuring expression of progressively more genes, measuring cholesterol, gender or BMI, measuring expression via a multiplex assay or PCR, and correlating the GE iAge to an immunological age. These limitations are not considered “meaningful limitations”. MPEP 2106.05(e) states: “The phrase "meaningful limitations" has been used by the courts even before Alice and Mayo in various contexts to describe additional elements that provide an inventive concept to the claim as a whole.” However, as will be discussed below, these limitations do not arrive at an inventive concept. In addition, as has been discussed, they represent insignificant extra-solution activity, i.e. “data gathering”.
MPEP 2106.05(f) raises the question as to whether the additional elements recited in the claim represent “mere instructions to apply an exception”. Here, the judicial exceptions are the natural correlation between gene expression and gene expression inflammatory age, mathematical concepts of multiplication and addition, and the mental process of comparing. The additional elements recited in the claims (i.e. specifically collecting blood or serum samples, measuring expression of progressively more genes, measuring cholesterol, gender or BMI, measuring expression via a multiplex assay or PCR, and correlating the GE iAge to an immunological age) does amount to mere instructions to apply the correlation, since the collection of particular biological samples, measuring gene expression of more genes, measuring other parameters of the subjects, and correlating values with each other serve as mere conventional steps taken for the purpose of gathering data about gene expression of the claimed genes, which any practical use of the natural correlation would require.
MPEP 2106.05(g) has to do with whether the additional elements of the claim amount to insignificant extra-solution activity. MPEP 2106.05(g) notes that “[d]etermining the level of a biomarker in blood” is an example of “mere data gathering” which the courts have found to be insignificant extra - solution activity. Likewise, MPEP 2106.05(g) notes that “[p]erforming clinical tests on individuals to obtain input for an equation” also represents insignificant extra-solution activity. This aligns closely with the instant claims, where the additional elements of the claims amount to gathering samples, measuring gene expression, and calculating a GE iAge.
MPEP 2106.05(h) has to do with whether the additional elements amount to more than generally linking the use of a judicial exception to a particular technological environment or field of use. Here, the recitation of the method being used to determine a subject’s GE iAge is considered a “field of use”. However, as MPEP 2106.05(h) indications, such limiting to a particular “field of use” does not confer patentability on otherwise ineligible subject matter.
Finally, in regards to MPEP 2106.5(d), claims that focus on the use of judicial exceptions must also include additional elements or steps to show that the inventor has practically applied, or added something significant to, the judicial exceptions themselves. See Mayo 101 USPQ2d at 1966. Adding steps to a judicial exception that only recite well-understood, routine, conventional activity previously engaged in by researchers in the field would not be sufficient. See id. At 1966, 1970. The claims identify blood cell types for testing, subjects to be tested, and assays for determining gene expression levels. The identification of sample types and subjects from which the samples are to be collected is routine in the art of medical testing. As stated in MPEP 2106.05(d), the courts have recognized certain laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity. One of these techniques is determining the level of a biomarker in blood by any means (see Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017)). Regarding the assays to detect gene expression, the assays claimed are routine in the art for measuring gene expression. Regarding the calculations, the claimed calculations are routine in the art for normalizing multiple regression data to determine a dependent variable. Regarding the mental process, it is routine in the art to compare test values and control values to determine an outcome. The claims use conventional means to observe all these judicial exceptions and therefore the steps of the claimed methods are not sufficient to transform unpatentable judicial exceptions into patentable applications of those regularities. This is also supported by the findings of in Ariosa Diagnostics, Inc. v. Sequenom, Inc., 115 USPQ2d 1152 (Fed. Cir. 2015), wherein the Federal Circuit held that claims that measure biological substances using methods that are routine and conventional do not amount to more than reliance on a correlation that is a law of nature for patentability.
In summary, claims 1, 2, 4-16, 18, and 20-23 are rejected under 35 U.S.C. 101 for being directed to judicial exceptions without significantly more. It is noted here, however, that paragraph [014] of the specification has treatment options that would be sufficient to overcome this rejection
Conclusion
All claims are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allison E Schloop whose telephone number is (703)756-4597. The examiner can normally be reached Monday-Friday 8:30-5 ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571) 272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/Robert T. Crow/Supervisory Patent Examiner Trainer, Art Unit 4100