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 .
Applicants are informed that further examination of the instant application will be conducted by Examiner Blumel. Contact information is provided below.
Priority
Acknowledgment is made of applicant's claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. PCT/IB2020/060314, filed on
11/03/2020.
Claims 12-20 are examined on the merits.
Specification
(Objection withdrawn in view of amendment) The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter.
Claim Objections
(Prior Objections Withdrawn) Claims 2, 3, and 10 are objected to because of the following informalities:
(New Objection Necessitated by Amendment) In claim 20, line 2, the acronym "PaO2/FiO2" is recited, but not defined in the claim. An acronym should be defined the first time it appears in the claims. For the purposes of examination, " PaO2/FiO2" is interpreted to mean enzyme-linked immunosorbent assay.
Claim Rejections - 35 USC § 112 35 USC § 112(b)
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.
(Rejections withdrawn in view of amendments) Claims 7, 9, and 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing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 35 U.S.C. 112, the applicant), regards as the invention.
(New Rejection Necessitated by Amendments) Claims 12-20 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 35 U.S.C. 112, the applicant), regards as the invention.
Claim 12 recites, “A method for generating a severity score… and …determining the severity score calculated based on a sum of the respiratory score and the PSP/reg score.” Claim 14 recites, “wherein the severity score further comprises biomarker score.” and claim 18 recites, “wherein the severity score is used for classifying patients into different severity levels”.
However, claims 12, 14 and 18 do not establish what degree or level of score would need to be reach for classification or what the classification is intended to achieve with regard to “into different severity levels”. Additionally, claim 12 indicates that it by itself can generate a severity score and therefore it is unclear if the biomarker score of claim 14 should be part of claim 12 since claim 14 also states that the biomarker score is also required as part of the severity score.
Claims 13, 15-17, 19 and 20 are also rejected because they depend from claim 12, but do not remedy this deficiency.
35 USC § 112(a)
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.
(Prior Rejection Maintained) Claims 12-20 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 claims contain 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.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a),
the Federal Circuit has developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8
USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors, to assess whether any
necessary experimentation required by the specification is "reasonable" or is "undue." The
factors considered include (A) the breadth of the claims; (B) the nature of the invention; (C) the
state of the prior art; (D) the level of one of ordinary skill in the art; (E) the level of predictability
in the art; (F) the amount of direction provided by the inventor; (G) the existence of working
examples; and (H) the quantity of experimentation needed to make or use the invention based
on the content of the disclosure.
Breadth of the claims and nature of the invention: Claims 12-20 are drawn to a method for generating a severity score for SARS in a patient, the method comprising:
“determining a level of pancreatic stone protein / regenerating protein (PSP/reg) in the body fluid sample;
determining a PSP/reg score based on the determined PSP/reg level of the patient;
determining a respiratory score based on a measured respiratory parameter of the patient; and determining the severity score calculated based on a sum of the respiratory score and the PSP/reg score.”
The severity score also comprises a biomarker score (claim 14).
Further limitations to the method include using C-Reactive Protein (CRP) as an additional biomarker score, the type of body fluid sample, how the respiratory score is obtained, how the PSP/reg level is determined.
State of the prior art and unpredictability in the art: According to the specification of the claimed invention, there are currently no known scoring systems to help clinicians sort and/or orient patients for better treatment. However, in the art, there are numerous scoring systems that can be employed by clinicians to determine the severity of a COVID-19 infection, as evidenced by Fan, Guohui, et. al., "Comparison of severity scores for COVID-19 patients with pneumonia: a retrospective study." (Published 09/10/2020; cited in Applicant's IDS submitted on 05/01/2023), hereby referred to as Fan, G., et. al.. For example, Fan, G., et. al. teaches about 7 different severity scores, including qSOFA, as a method to accurately predict the risk of death in patients presenting with COVID-19 pneumonia (paragraph 1). However, Fan, G., et. al. does not teach the individual factors, including the biomarkers, that go into the calculation of each score nor does it teach how to calculate the different scores. In summary, Fan, G., et. al. demonstrates a high level of unpredictability in the determination of severity scores for assessing the likelihood of a patient to develop severe COVID-19.
Further in the art, Stolz, D., and Frederic, L., (WO 2011151783, Published 12/08/2011;
Cited in Applicant's IDS on 05/01/2023) teaches a method of assessing PSP/reg concentrations in
the blood as part of a method to determine the prognosis of a patient with diseases of the airways
and lungs, including lower respiratory tract infections. Stolz, D., and Frederic, L. teach that
PSP/reg is highly upregulated in the blood after trauma, especially in patients with sepsis, and is
related to the severity of inflammation (background of the invention, page 1, paragraphs 3 and
4). Stolz, D., and Frederic, L. further teach the level of PSP/reg in a body fluid sample can be used in conjunction with other biomarkers to indicate the development and severity of lower
respiratory tract infections (PSP/reg levels are predictor of outcome, page 13).
To summarize, the prior art, as of 05/01/2023, does not provide evidence for assessing
the severity of COVID-19 using a combination of PSP/reg levels and a respiratory score to yield a severity score, but does teach the combination to assess the severity of lower respiratory tract
infections.
Those with relevant skill in the art: The level of skill in the art is that of Ph.D.-level scientists and medical doctors (D.O. and/or M.D.).
Amount of direction and existence of working examples: The instant application teaches two
working examples, neither of which represent an example of the claimed method wherein the
severity score is calculated based on an exemplary patient's respiratory and PSP/reg scores. Thus,
the instant application offers no reasonable guidance or direction to use the claimed method for
assessing the severity of SARS, namely COVID-19, in a patient.
The closest working examples are in instant paragraph 0024 and instant figure 1, hereby
referred to as example 1, and instant paragraphs 0026 and 0027 and instant figures 3 and 4,
hereby referred to as example 2. Example 1 teaches the different components of the respiratory
and PSP/reg scores and general formula to determine the severity score. For example, under
broadest reasonable interpretation, example 1 teaches that a patient with no breathing problems
and a PaO₂/FiO₂ value greater than 400 mmHg would have a RESP score of 0. Additionally, instant paragraph 0026 and figure 4 teach when a patient should be sent home versus when
hospitalization should be considered based on the severity score. For example, a patient
presenting with a cSOFA score of 0 has a low probability of developing severe COVID-19 and
should be sent home.
The instant application has no examples of how difficulty of breathing is measured as part
of the respiratory score, how the PaO₂/FiO₂ is measured as part of the respiratory score, how a
patient with respiratory system (practitioner appreciation) and PaO₂/FiO₂ values that fall in
different RESP score categories would be scored, how the PSP/regvalue is determined as part of
the PSP/reg score, or how to perform the severity score calculation based on the respiratory and
PSP/reg scores. Moreover, the instant application does not teach any reference values, including
for respiratory rates, PaO₂/FiO₂, and PSP/reg, that are considered normal.
Quantity of experimentation needed: Undue experimentation would be required to practice the
claimed invention commensurate with the scope of the claims, as discussed above. Reasonable
correlation must exist between the scope of the claims and scope of enablement set forth. It
would take undue trials and errors to practice the claimed invention in view of the quantity of
experimentation necessary, the limited working examples, the unpredictability of the art, the
lack of sufficient guidance in the specification, and the breadth of the claims.
Response to arguments:
Applicant presents the following arguments in traversal of the rejection:
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., obtaining a SOFA or cSOFA score) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
In addition, claim 12 ends with the limitation of “determining the severity score calculated based on a sum of the respiratory score and the PSP/reg score”. However, once this sum is calculated, what is does this result in. What summation amount or level is important or should be ignored? The specification does not enable one of ordinary skill in the art to carry out the claimed method and obtain a severity score which can then be used to classify a patient (claim 18) or being used to support a healthcare unit (claim 19). The degree or level of the severity score is not defined in such a way that one of ordinary skill in the art can act it, which appears to be part of the intent of the method of claims 12-20. Therefore, the claimed method is interpreted to lack enablement for generating a severity score of a patient that has or might have SARS and further assigning the patient a classification or being used in a healthcare unit.
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.
(New Rejection Necessitated by Amendments) Claims 12-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite "generating a severity score for severe acute respiratory syndrome in a patient" by employing several “determining” steps. This judicial exception is not integrated into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set for below.
The claims are drawn to a method to assess the severity of SARS in a patient by
determining the level of PSP/reg in a body fluid sample that is correlated with a respiratory
system score. As such, the claimed method, which is drawn to a process, falls into one of the four
categories of patent eligible subject matter (i.e., process, machine, manufacture, or composition
of matter) (Step 1: YES).
The claims are drawn to a judicial exception of an abstract idea, specifically mental processes and mathematical concepts (Step 2A, Prong One: YES). For example, starting at line 3 of claim 12, it is recited:
“determining a level of pancreatic stone protein / regenerating protein (PSP/reg) in the body fluid sample;
determining a PSP/reg score based on the determined PSP/reg level of the patient;
determining a respiratory score based on a measured respiratory parameter of the patient; and determining the severity score calculated based on a sum of the respiratory score and the PSP/reg score.”
The severity score also comprises a biomarker score (claim 14).
These scores use a mathematical formula to convert tangible biomarkers, such as increased PSP/reg in the blood, into an objective value and thus are considered an abstract idea in the mathematical concept grouping. Since these scores could be practically calculated in the human mind, they are also considered an abstract idea in the mental process grouping.
These acts of evaluating information can practically be performed in the human mind and thus are considered an abstract idea in the mental process grouping. For example, a person having ordinary skill in the art could count in their mind how many breaths a patient is taking per minute to deduce if they are having difficulty breathing.
Although the claims recite specific body fluid samples, particular thresholds for the
severity score, and methods of determining the PSP/reg value and the use of assays to determine the level of PSP/reg, the claims as a whole are not limited to a particular method and constitutes a generic instruction to assess the severity of SARS.
Further, generally linking the use of the judicial exception to a particular technological
environment or field of use is not indicative of integration into a practical application. There are
thus no additional elements recited in the claims that integrate the judicial exception into a
practical application (Step 2A, Prong Two: NO). The claimed invention does not use or apply the
judicial exception in a meaningful way to contribute to an inventive concept or amount to
significantly more than the judicial exception (Step 2B: NO). Thus, the claims fail the subject
matter eligibility test (Steps 1 and 2A, Prong One: YES; Steps 2A, Prong Two and 2B: NO) and are not eligible subject matter. See MPEP § 2106 and 2173.05(q).
Response to arguments:
Applicant’s arguments have been considered, however, they are not persuasive. Similar to claims 1-10 previously presented, the instant method involves providing a body fluid sample from a patient and determining a level of PSP/reg and a score of PSP/reg, a respiratory score based on a measured respiratory parameter of the patient and determining the severity score calculated based on a sum of the respiratory score and the PSP/reg score. The severity score further comprises a biomarker score.
However, the presently claimed method does not integrate the judicial exception into a practical application. The determining steps are recited at a high level of generality and it would appear that the active steps are “providing a body fluid” and using ELISA (claim 17), for example, to determine the level of PSP/reg.
(Rejection withdrawn in view of amendments) Claim 11 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
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.
(Prior Rejection Maintained) Claims 12-20 are rejected under 35 U.S.C. 103 as being unpatentable over Stolz, D., and Frederic, L., (WO 2011151783, Published 12/08/2011; Cited in Applicant's IDS on 05/01/2023) in further view of Fan, Guohui, et. al., (Published 09/10/2020; Cited in Applicant's IDS on 05/01/2023).
The claimed invention is interpreted as being drawn to analyzing PSP/reg levels, respiratory scores and biomarker (CRP) levels in a patient suspected of having SARS, caused by SARS-CoV-2.
Stolz, D., and Frederic, L. teach a method to determine the level of PSP/reg in body fluid
samples of a patient and sorting patients according to risk (page 1, lines 6 - 9; claim 1), as recited in instant claim 12. It is further taught that the body fluid sample from said patient (page 5, line 20; claim 2) include samples of whole blood, serum, plasma, urine, sputum, cerebrospinal fluid, tear fluid, sweat, milk, and extracts from solid tissue or from fecal matter (page 4, lines 20 - 22),
as mentioned in instant claim 16. Stolz, D., and Frederic, L. go on to teach the level of
PSP/reg in said sample is determined (page 5, line 21; claim 12) using ELISA, RIA, EIA, mass
spectrometry, or microarray analysis (page 7, lines 3 – 6; claim 3 and 6), as mentioned in instant claims 16-17. Page 5, lines 22 - 25 continue to teach that the determined level of PSP/reg is compared with a reference value, wherein a PSP/reg level below or equal to 24 ng/mL is predictive of a good chance of health (page 9, lines 20 - 22), but a level of 200 ng/mL or higher is indicative of a severe infection and predictive of mortality (page 9, lines 24 - 25; claim 10). It is further taught that other inflammatory biomarkers, including C-reactive protein (CRP), were measured alongside PSP/reg as an indicative for short and long-term outcomes (page 14, lines 15 - 19), as mentioned in instant claims 14-15. Stolz, D., and Frederic, L. go on to teach that additional information, including body temperature, heartrate, PaO₂/FiO₂, oxygen saturation, mechanical ventilation status (page 12, lines 15 - 19), were also collected to yield a respiratory score known as sequential organ failure assessment (SOFA) scores (page 10, lines 19 - 21), wherein the SOFA scores were correlated with PSP/reg levels to determine survival likelihoods (PSP/reg correlated with SOFA; page 13, lines 10 - 14; Figure 1), as recited in instant claim 12 and 18-20.
Stolz, D., and Frederic, L. fail to teach employing their method of analyzing PSP/reg levels, respiratory scores and biomarker (CRP) levels in a patient suspected of having SARS, caused by SARS-CoV-2, as required in instant claims 12 and 13. However, Fan, G., et. al. teaches that current score rules, including quick SOFA (qSOFA), have sensitivity and specificity for identifying COVID-19 patients at risk of death (page 2, paragraphs 2-5).
Stolz, D., and Frederic, L. and Fan, G., et. al. are considered to be analogous to the claimed invention because both are in the same field of utilizing biomarkers to indicate the severity of an infection. Stolz, D., and Frederic, L. teach that their method is for the diagnosis and prognosis of lower respiratory tract infections that can be caused by bacteria, viruses, fungi, or parasites (page 3, lines 17 - 21). A person having ordinary skill in the art would know that infection with SARS-CoV-2, a virus, results in COVID-19, which is a respiratory disease. Additionally, one with skill in the art would know that SARS results from infection of the lower respiratory tract. Thus, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have combined the determination of PSP/reg levels with the additional scores mentioned in Fan, G., et. al. to speed up and improve the assessment of the severity of SARS (instant application - page 4, paragraph 0016). The Supreme Court has decided that a claim can be proved obvious merely by showing that the combination of known elements was obvious to try. In this regard, the Supreme Court explained that, "[W]hen there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill in the art has a good reason to pursue the known options within his or her technical grasp." An obviousness determination is not the result of a rigid formula disassociated from the consideration of the facts of the case. Indeed, the common sense of those skilled in the art demonstrates why some combinations would have been obvious where others would not. Therefore, choosing from a finite number of identified, predictable solutions, with a reasonable expectation for success, is likely to be obvious to a person if ordinary skill in the art. See KSR International Co. V. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) and MPEP § 2143E and 2143.02.
Response to arguments:
Applicant’s arguments have been considered, however, they are not persuasive::
Stolz, D., and Frederic, L. teach analyzing a biological sample for PSP/reg and obtaining score. They also go on to teach that additional information, including body temperature, heartrate, PaO₂/FiO₂, oxygen saturation, mechanical ventilation status (page 12, lines 15 - 19), were also collected to yield a respiratory score known as sequential organ failure assessment (SOFA) scores (page 10, lines 19 - 21), wherein the SOFA scores were correlated with PSP/reg levels to determine survival likelihoods (PSP/reg correlated with SOFA; page 13, lines 10 - 14; Figure 1). Therefore, it would appear that Stolz and Frederic carrying out the determining steps presently claimed. While they do not mention SARS or SARS-CoV-2 specifically, these deficiencies are remedy by the teachings of Fan, G., et. al. Fan, G., et. al. teach that current score rules, including quick SOFA (qSOFA), have sensitivity and specificity for identifying COVID-19 patients at risk of death. Therefore, the teachings of the cited prior art render obvious the instant invention as claimed.
Conclusion
Claims 12-20 are rejected. No claims are allowed.
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 BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached at (571) 270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
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