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 .
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 on 16 May 2024. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Specification
The Specification is objected to because the drawings are indicated by “Figure” rather than “FIG.” as required by 37 C.F.R. § 1.84 (u)(1) (see also MPEP §608.02 (V)).
The incorporation of essential material in the specification by reference to an unpublished U.S. application, foreign application or patent, or to a publication is improper.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).
The use of the term BiophytisTM BIO0101, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Drawings
The drawings are objected to because the drawings are indicated by “Figure”
rather than “FIG.” as required by 37 C.F.R § 1.84 (u)(1) (see also MPEP § 608.02 (V)).The different views must be numbered in consecutive Arabic numerals, starting with 1,independent of the numbering of the sheets and, if possible, in the order in which they appear on the drawing sheet(s). Partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter. View numbers must be preceded by the abbreviation “FIG.” Where only a single view is used in an application to illustrate the claimed invention, it must not be numbered and the abbreviation “FIG.” must not appear.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended
replacement drawing sheet should include all of the figures appearing on the immediate
prior version of the sheet, even if only one figure is being amended. The figure or figure
number of an amended drawing should not be labeled as “amended.” If a drawing figure
is to be canceled, the appropriate figure must be removed from the replacement sheet,
and where necessary, the remaining figures must be renumbered and appropriate
changes made to the brief description of the several views of the drawings for
consistency. Additional replacement sheets may be necessary to show the renumbering
of the remaining figures. Each drawing sheet submitted after the filing date of an
application must be labeled in the top margin as either “Replacement Sheet” or “New
Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner,
the applicant will be notified and informed of any required corrective action in the next
Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 2 and 16 are objected to because of the following informalities: “SARS Cov-2” should read “SARS-CoV-2”.
Claims 13 is objected to because of the following informalities: “IN01Vaccine” should read “IN01 Vaccine”.
Appropriate correction is required.
Claim Interpretation
The term “Angiotensin (1-7)” is the proper name of a vasoactive peptide of the renin-angiotensin system as evidenced by Alenina, et al. (The Protective Arm of the Renin Angiotensin System (RAS). 2015:155–9.)
Claim Rejections - 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.
Claim 2, 9-10, 12, and 14 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 term "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 2, the term “COVID-19” in parentheses in line three renders the claim indefinite. As COVID-19 is the disease caused by the SARS-CoV-2 infection, it is unclear if the limitations of the claim are including COVID-19 or not.
Regarding claims 9-10, and 12-14, the term “utilizing” renders the claims indefinite. The term is not defined by the claim or the specification. It is unclear how the drugs are being “utilized”. For the purposes of compact prosecution and applying prior art the term “utilizing” is being understood as “treating through administration of the drugs ”.
Regarding claim 10, the term “(soluble)” renders the claim indefinite because it is unclear whether the limitation(s) within the parentheses are part of the claimed invention or an example.
Claim 10 contains the trademark/trade name BiophytisTM BIO0101. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a MasR agonist and, accordingly, the identification/description is indefinite.
It is noted that any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejection and art may be readily applied in a subsequent final Office action.
Claim Rejections - 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.
Claim 10 is 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.
Claims are required to be self-contained and be able to be read without any outside information. Claim 10 references a foreign patent (EP2967049). “Essential material” may be incorporated by reference but only by way of U.S. patents or U.S. patent application publications, which patent or patent application publication does not itself incorporate such essential material by reference. See MPEP 608.01(p) and 37 CFR 1.57(d).
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 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. This judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
The instant claims are drawn to a method of predicting whether a patient infected by a viral respiratory disease is at risk of developing clinical complications, which is a statutory category of invention (STEP 1: YES).
The instant claims are directed to the natural correlation between the levels of certain proteins in their blood and their risk of developing clinical complications. The instant claims further encompasses the mental step of appreciating the natural correlation to determine whether or not a person is at risk of developing clinical complications. As such, the instant claims recite judicial exceptions (JE) in the form of a law of nature and abstract idea (STEP 2A, PRONG ONE: YES).
The crux of the claimed method is the natural correlation and appreciation thereof to determine whether or not a person will develop clinical complications. Claims 9-10 and 12-15 add the step of treating some patients, the broadest interpretation of these claims also includes not treating patients, as the claims require a patient to meet certain requirements for treatment. So, while certain embodiments of claims 9-10 and 12-15 are eligible (treating patients) others (not treating patients) are ineligible due to only requiring the appreciation of the natural correlation and the mental step of deciding to treat or not treat based on this correlation. The remaining instant claims (1-8, 11, and 16-20) do not recite, e.g. any particular treatment or prophylaxis for the levels detected; rather the remaining claims only require the appreciation of the natural correlation between the blood concertation levels and disease outcome. As such, the instant claims do not recite additional elements that integrate the JE into a particular application (STEP 2A, PRONG TWO: NO).
As discussed in detail below, it was well-understood, routine, and conventional (WURC) at the time of filing to measure different protein levels in the blood of patients and use the results to determine if a patent would develop clinical complications (see rejections of record under 35 U.S.C. §103 below). As such, beyond the JE, the instant claims only recite WURC data-gathering steps. These WURC data-gathering steps constitute insignificant extra-solution activities, which does not reasonably provide an inventive concept. As such, the instant claims do not recite significantly more than JE (STEP 2B: NO).
Accordingly, the instant claims do not constitute patent eligible subject matter under 35 U.S.C. §101.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 7-10, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Omland, et al. (EP 3943946 A1, hereinafter “Omland”) and further in view of Henry, et al. (Med Virol. 2021 Feb;93(2):678-680., NPL-IDS, filed, 05/28/2024, hereinafter “Henry”).
Regarding claims 1 and 16, Omland teaches a method for predicting the disease severity in a patient with COVID-19 by determining the level of GDF-15 in a patient with COVID-19 and comparing the levels to a reference and then predicting the disease severity (Abstract). The references include healthy samples, known diseased samples, and samples with known disease severity (¶0050-0053). Omland does not teach using Angiotensin (1-7) levels to determine COVID-19 disease severity. However, Henry teaches that Angiotensin (1-7) can be used to predict COVID-19 severity in patients as patients who were admitted to the ICU due to more severe symptoms had lower concentrations of Angiotensin (1-7) in their blood than patients with lesser symptoms that did not require ICU admittance (Figure 1C).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have combined the teachings of Omland for a method of determining the severity of disease in COVID-19 patients using GDF-15 with the teachings of Henry for the correlation between COVID-19 disease severity and Angiotensin (1-7). Adding a second marker for disease severity would increase the sensitivity of the diagnoses. One of skill in the art would have had a reasonable expectation of success in combining Omland and Henry because they both teach COVID-19 disease severity markers.
Regarding claims 7-8, Henry teaches measuring Angiotensin (1-7) levels via ELISA (pg. 679, column 1).
Regarding claims 9-10, Henry teaches TXA127 as a COVID-19 treatment (pg. 678, column 1).
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Omland and Henry as applied to claims 1, 7-10, and 16 above, and further in view of Martins, et al. (RJ Open Res. 2021 Aug 2;7(3):00114-2021., NPL-IDS, filed 05/28/2024, hereinafter “Martins”).
As discussed above claims 1, 7-10, and 16 were rendered prima facie obvious over Omland and Henry.
Regarding claim 2, Omland and Henry do not teach that the Angiotensin (1-7) level is higher in COVID-19 patients compared to healthy patients, but this property is, absent evidence to the contrary, inherent to the method taught by Omland and Henry. However, the method taught by Omland and Henry requires the appreciation of the higher angiotensin (1-7) levels in COVID-19 patients. Martins teaches that patients infected with SARS-CoV-2 have higher angiotensin levels than non-SARS-CoV-2 infected controls (Figure 1 d-e, 3rd panel), which allows one of skill in the art to use Martins as a baseline for predicting a patient’s outcome by measuring Angiotensin (1-7) levels.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have combined the teachings of Omland and Henry for a method of predicating disease severity in patients infected with SARS-CoV-2 using GDF-15 and Angiotensin (1-7) with the teachings of Martins for comparing the levels of Angiotensin (1-7) between infected and non-infected patients. Comparing non-infected and infected controls allows for a baseline and correlation to be established for future experiments. One of skill in the art would have had a reasonable expectation of success in combining Omland, Henry, and Martins because they all teach using biomarkers to determine disease outcomes.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Claims 3 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Omland and Henry as applied to claims 1, 7-10, and 16 above, and further in view of d’Alessandro, et al. (J Med Virol. 2020 Oct;92(10):2216-2220., hereinafter “d’Alessandro”).
As discussed above claims 1, 7-10, and 16 were rendered prima facie obvious over Omland and Henry.
Regarding claims 3 and 11, Omland and Henry do not teach measuring the biomarker KL-6 in infected patients. However, d’Alessandro teaches that patients with severe COVID-19 have significantly higher levels of KL-6 compared to both non-severe COVID-19 patients and healthy controls.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have combined the teachings of Omland and Henry for a method of determining the severity of disease in COVID-19 patients using GDF-15 and Angiotensin (1-7) with the teachings of d’Alessandro for the correlation between COVID-19 disease severity and KL-6 blood concentration. Adding additional marker for disease severity would increase the sensitivity of the diagnoses. One of skill in the art would have had a reasonable expectation of success in combining Omland, Henry, and d’Alessandro because they all teach COVID-19 disease severity markers.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Omland and Henry as applied to claims 1, 7-10, and 16 above, and further in view of Timurkaan, et al. (F.U. Med.J.Health.Sci. 2022; 36 (1): 46 - 50, hereinafter “Timurkaan”).
As discussed above claims 1, 7-10, and 16 were rendered prima facie obvious over Omland and Henry.
Regarding claim 4, Omland and Henry do not teach measuring the biomarker TGFβ in infected patients. However, Timurkaan teaches that patients with severe COVID-19 symptoms that appear on a CT scan have significantly higher levels of TGFβ compared to both non-severe COVID-19 patients (CT negative) (figure 5) and healthy controls (figure 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have combined the teachings of Omland and Henry for a method of determining the severity of disease in COVID-19 patients using GDF-15 and Angiotensin (1-7) with the teachings of Timurkaan for the correlation between COVID-19 disease severity and TGFβ blood concentration. Adding additional marker for disease severity would increase the sensitivity of the diagnoses. One of skill in the art would have had a reasonable expectation of success in combining Omland, Henry, and Timurkaan because they all teach COVID-19 disease severity markers.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Omland and Henry as applied to claims 1, 7-10, and 16 above, and further in view of Henry, et al. (Am J Emerg Med. 2020 Sep;38(9):1722-1726., hereinafter “Henry2”).
As discussed above claims 1, 7-10, and 16 were rendered prima facie obvious over Omland and Henry.
Regarding claim 5, Omland and Henry do not teach measuring the biomarker LDH in infected patients. However, Henry2 teaches elevated LDH values are associated with a 6-fold increase in odds of severe COVID-19 disease (pg. 1726, column 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have combined the teachings of Omland and Henry for a method of determining the severity of disease in COVID-19 patients using GDF-15 and Angiotensin (1-7) with the teachings of Henry2 for the correlation between COVID-19 disease severity and LDH blood concentration. Adding additional marker for disease severity would increase the sensitivity of the diagnoses. One of skill in the art would have had a reasonable expectation of success in combining Omland, Henry, and Henry2 because they all teach COVID-19 disease severity markers.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Claims 6 and 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Omland and Henry as applied to claims 1, 7-10, and 16 above, and further in view of Serdar, et al. (Biochem Med (Zagreb). 2021 Feb 15;31(1):010502. hereinafter “Serdar”).
Regarding claims 6 and 17-20, Omland and Henry do not explicitly teach how many healthy patients or patients with poor and favorable outcomes are tested and used as baseline controls to predict future patient outcomes. However, Omland does teach that typically 100 well-characterized individuals from the appropriate reference population would be used to establish a baseline or reference value (¶0052) and routine optimization of the correct number of reference patients would have led to the appropriate amount of reference samples tested. Serdar teaches that sample size is directly related to the power of the results and sensitivity (Figure 2). Increasing the number of reference samples decreases the change for false positives and negatives (Figure 2). One of skill in the art would have found it obvious to optimize the number of patients that the Angiotensin (1-7) levels are tested on to ensure that enough patients are tested to decreased the probability of false positives and negatives.
As discussed above claims 1, 7-10, and 16 were rendered prima facie obvious over Omland and Henry.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Claims 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Omland and Henry as applied to claims 1, 7-10, and 16 above, and further in view of Chaudhary, et al. (Front Med (Lausanne). 2020 Sep 9;7:539. hereinafter “Chaudhary”).
As discussed above claims 1, 7-10, and 16 were rendered prima facie obvious over Omland and Henry.
Regarding claims 12-13, Omland and Henry do not teach treating severe COVID-19 disease patients with anti-fibrotics. However, Chaudhary teaches that anti-fibrotics can be used in cases of severe COVID-19 disease that causes lung fibrosis (abstract). Henry teaches that patients not admitted to the ICU have higher Angiotensin (1-7) levels than those admitted to the ICU (figure 1c).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have combined the teachings of Omland and Henry for a method of determining the severity of disease in COVID-19 patients using GDF-15 and Angiotensin (1-7) with the teachings of Chaudhary for treating severe COVID-19 disease that results in lung fibrosis with anti-fibrotics. Chaudhary provides motivation by teaching that anti-fibrotics are used to treat a severe complication of COVID-19, lung fibrosis (Abstract). One of skill in the art would have had a reasonable expectation of success in combining Omland, Henry, and Chaudhary because they all teach severe COVID-19 disease.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Claims 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Omland and Henry as applied to claims 1, 7-10, and 16 above, and further in view of Gupta, et al. (N Engl J Med. 2021 Nov 18;385(21):1941-1950., hereinafter “Gupta”).
As discussed above claims 1, 7-10, and 16 were rendered prima facie obvious over Omland and Henry.
Regarding claims 14-15, Omland and Henry do not teach treating severe COVID-19 disease patients with anti-fibrotics. However, Gupta teaches that the spike specific monoclonal antibody, sotrovimab, reduces disease progression in high-risk patients with mold-moderate COVID-19. Henry teaches that patients not admitted to the ICU have higher Angiotensin (1-7) levels than those admitted to the ICU (figure 1c).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have combined the teachings of Omland and Henry for a method of determining the severity of disease in COVID-19 patients using GDF-15 and Angiotensin (1-7) with the teachings of Gupta for treating COVID-19 disease in high-risk patients with sotrovimab. Gupta provides motivation by teaching that sotrovimab is used to treat a high-risk COVID-19 patients to prevent disease progression (Abstract). One of skill in the art would have had a reasonable expectation of success in combining Omland, Henry, and Gupta because they all teach COVID-19 disease.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Conclusion
NO CLAIMS ARE ALLOWED
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/CASSANDRA SENN GRIZER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
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