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 .
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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.
The incorporation of essential material in the specification by reference to an unpublished U.S. application, foreign application or patent, or to a publication is improper. Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g).
Claim Rejections - 35 USC § 112
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 10, 16, and 17 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.
Claim 10 recites a temperature limitation of “>40 to 54oC.” The scope of this limitation is unclear because the language can reasonably be interpreted to encompass either (a) any temperature greater than 40oC or (b) a temperature within a bounded range of 40oC to 54oC. As a result, the metes and bound of the claim are not certain. For the purposes of compact prosecution, the examiner has interpreted the limitation to mean a temperature between 40 and 54oC.”
Claims 16 and 17 are indefinite in that it is unclear which biomarkers are being required. It appears as if applicant is splitting the biomarkers into four sets:
HSPA1A, HSPA1B, HSPA6, HSPA4L
HSPB1
DNAJA4, DNAJB1, DNAJB4
FKBP4
Therefore, claim 16 reads as “the at least two biomarkers…comprising at least one of Set 1, Set 2, at least one of Set 3, and Set 4.” This language is ambiguous as to whether (a) only two biomarkers are required, (b) one biomarker from each identified set is required, or (3) if one biomarker must be selected from at least the specific identified sets (Set 1 and 3). Similarly, claim 17 reads as “the at least two biomarkers…comprising Set 1, Set 2, Set 3, and Set 4” which is ambiguous as to whether the claim requires all the biomarkers from each listed set, or merely the recited minimum of “at least two biomarkers.” For the purposes of prior art, examiner has determined the broadest reasonable interpretation of the claims requires only the recited minimum number of biomarkers, without requiring inclusion of specific sets or members thereof.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 16 and 17 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
As discussed previously, under the broadest reasonable interpretation, the claims require only the recited minimum number of biomarkers, without requiring inclusion of specific sets or members thereof. Accordingly, claims 16 and 17 do not impose any additional limitation beyond those already required by claim 1 and therefore do not further limit the claim from which they depend.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim 1-17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more.
Subject Matter Eligibility Test (see MPEP § 2106):
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter?
Yes, the claims are directed towards “a method for diagnosing a heatstroke in a heatstroke subject” (a process).
Step 2A: Are the claims directed to a judicial exception?
Prong 1: Do the claims recite an abstract idea, law of nature, or a natural phenomenon?
Yes, the claims describe a consequence of a natural phenomenon, e.g. the naturally-occurring relationship between the presence of altered RNA biomarker expression and the manifestation of heatstroke. See MPEP 2106.04(b)I.(iv-v).
Prong 2: Do the claims recite additional elements that integrate the judicial exception into a practical application?
Claim 1 indicates the method is to be used for “diagnosing a heatstroke.” Simply diagnosing based on test results is considered insignificant extra-solution activity (i.e. data gathering) because it merely interprets the detected natural correlation and does not impose meaningful limits that apply the judicial exception in a concrete technical or physical manner. As described by MPEP 2106.05(g), the term "extra-solution activity" can be understood as activities incidental to the primary process or product that are merely a nominal or tangential addition to the claim. Extra-solution activity includes both pre-solution and post-solution activity.
The additional limitations of claims 2-17 include, but are not limited to, symptoms, sample type, detection method, and subject characteristics. These can also be considered to be insignificant extra-solution activity.
Therefore, the addition of these additional elements do not integrate the recited exception into a practical application.
Claims 18 and 19 add limitations for the treatment of an individual suffering from heatstroke. According to MPEP 2106.04(d)(2), one way to demonstrate integration of the judicial exception into a practical application is when the additional limitations “effect a particular treatment or prophylaxis for a disease or medical condition. The application or use of the judicial exception in this manner meaningfully limits the claim by going beyond generally linking the use of the judicial exception to a particular technological environment, and thus transforms a claim into patent-eligible subject matter.” Therefore, claims 18 and 19 contain eligible subject matter.
Step 2B: Do the claims recite additional elements that amount to significantly more than the judicial exception?
The additional limitations of claims 1-17 are considered insignificant extra-solution activity and do not amount to significantly more than the judicial exception either individually or when taken together.
In summary, claims 1-17 do not contain 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.
Claims 1, 3, 5-7, 9, 10, and 12-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sonna (Sonna LA et al. 2004 May;96(5):1943-53) as evidenced by Wikipedia (Climate of South Carolina. Wikipedia. 2006) and the National Oceanic and Atmospheric Administration (NOAA) (Heat Index Chart. NOAA. 2022).
Regarding claims 1 and 12-17, Sonna compared the gene expression of individuals suffering from a heatstroke to control individuals in order to identify gene which are differentially expressed as a result of the heatstroke [abstract]. From this data, Sonna identified many differentially expressed genes including: HSPA70 (HSPA1A, HSPA1B, HSPA6), HSP27 (HSPB1), HSP40 (DNAJB1) and HSP56 (FKBP4) [Table 7].
Regarding claim 3, the individuals in Sonna’s study were specifically suffering from exertional heat injury (EHI) [abstract].
Regarding claim 5, peripheral blood mononuclear cell (PBMC) RNA samples were collected from each participant [abstract].
Regarding claims 6 and 7, the EHI individuals were identified by presenting symptoms such as having a core temperature ranging from 39.3 to 42.5oC [abstract], collapse during exertion, malaise, disorientation, ataxia, laboratory evidence of organ dysfunction [p1944 C1] and confusion [Table 2].
Regarding claims 9 and 10, the study’s subjects were marines participating in boot camp at Parris Island, South Carolina during the months of July, August, and September 2020. While no historic weather data is available for that area specifically, the mean heat index for Charleston Airport (the closest area with historical data available) in those months is 41oC, 39oC, and 35oC (respectively), as calculated from temperature and dew point data from Wikipedia using the NOAA head index chart.
Regarding claims 17 and 18, each heatstroke subject received treatment via active cooling, first on the field and then in the clinic through the use of ice blankets, showering, and intravenous hydration [p1944 C1]. In all cases, the internal temperature of the subject was reduced post-treatment as compared to pre-treatment [Table 2].
Claim Rejections - 35 USC § 103
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.
Claims 1, 2, 4-6, 8, and 11-14 are rejected under 35 U.S.C. 103 as being unpatentable over Bouchama (Bouchama A et al. Scientific reports. 2017 Aug 25;7(1):9429).
Regarding claims 1, 4, and 12-14, Bouchama compared the gene expression of individuals before and after being exposed to extreme environmental heat [abstract]. From this data, Bouchama identified many differentially expressed genes including: HSPA1A, HSPA1B, and DNAJB1 (Supplemental Tables 2 and 5).
Bouchama did not teach that these individuals were suffering from heatstroke.
However, the purpose of the study was not to mimic the long duration of heat exposure experience during heat waves (page 10) and thus induce heatstroke in the participants. Instead, the goal was to identify potential metabolic and signaling pathways that are modified upon exposure to extreme environmental heat (page 10). A skilled artisan looking to develop a method for detecting heat stroke in a patient would understand that the modified pathways would be expressed in a similar manner in individuals suffering from heat stroke, and thus the identified markers would be relevant to such a goal. In support of this rationale, Bouchama teaches that their findings suggest that exposure to heat alone could predict symptoms observed among victims of heatstroke, “thereby validating…the pertinence of [their] experimental model (page 10).”
Regarding claim 2, Bouchama validated the microarray data by performing multiplexed quantitative RT-PCR of randomly selected genes which showed differential expression. This demonstrates that RT-PCR is a practical method of analyzing differential expression of a selection of already identified genes (page 12).
Regarding claim 5, PBMC samples were collected from each participant (page 2).
Regarding claims 6 and 8, participants reported experiencing headache, dizziness, and nausea as a result of heat exposure, with one participant’s core temperature reaching 39oC (page 2).
Regarding claim 11, the participants were subjected to a temperature of ~76oC for 15 minutes (page 2). While Bouchama does not explicitly teach that their participants were amateur/profession athletes or laborers, they were rigorously selected based upon age, ethnicity, fitness, and health status in order to minimize discrepancies caused by genetic factors (page 10) and were, broadly speaking, 20-23 years old with METs of 10-12.6 (Table 1). With this in mind, it would be obvious to the skilled artisan that the results of Bouchama would apply to the claimed individuals as there is significant overlap between the two groups.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kara N Kovach whose telephone number is (571)272-8134. The examiner can normally be reached Monday - Friday, 9am - 3pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at (571) 272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N.K./ Examiner, Art Unit 1681
/SAMUEL C WOOLWINE/ Primary Examiner, Art Unit 1681