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 .
Status of the Claims
Claims 1-14 are pending and examined herein.
Claim Objections
Claims 1, 4-7, and 13-14 are objected to because:
Claims 1, 5, and 13 recite “a sample of said subject”, should be “a sample from said subject”.
Claim 4 contains abbreviations SELDI, MALDI, MALDI-Q TOF, MS/MS, TOF-TOF, and ESI-Q-TOF. These should be completely spelled out.
Claims 5, 6, and 14 recite “a sample of a subject” and “a sample of the same subject”, should be “a sample from a subject” and “a sample from the same subject”.
Claim 7 recites “the sample is body fluid”, should be “the sample is a body fluid”.
Claim 14 does not end in a period (see MPEP 608.01(m)).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL. —The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4, 7-9, and 13 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. This is a written description rejection.
Claims 1 and 13 recite a method of predicting a sepsis condition in a subject, wherein an elevated biomarker level is indicative of the risk of the sepsis condition.
As recited, the invention is directed to measuring a level of biomarker of structure (I) and using the measured level for predicting a risk of a sepsis condition.
State of the prior art & level of predictability in the art.
The prior art is silent on measuring a level of biomarker of structure I (BM1) and using the measured level for predicting a risk of a sepsis condition. The art of predicting a risk of a sepsis condition is highly unpredictable.
The level of one of ordinary skill is high with an ordinary practitioner possessing a PhD and related post-doctoral research experience.
Amount of direction and example provided by the inventor.
The specification is silent with respect to predicting actual risk of a sepsis condition. Seven examples present in the specification disclose the following information:
Example 1: Materials and methods for the detection of BM1 in serum, plasma, and urine. The example discloses sample preparation, analytical equipment, separation, and statistical analysis of the results (pg. 26-31).
Example 2: Determination of BM1 Levels in healthy human or non-human animal subjects. The example discloses the biomarker levels in healthy human and non-human subjects (pg. 32).
Example 3: Comparison of BM1 Levels in healthy subjects with subjects at risk of suffering from sepsis. The example discloses the biomarker levels from “patients suffering from sepsis or septic shock, or from non-septic patients diagnosed with heart failure (=control group)” (pg. 32, lines 27-29).
The only sepsis diseases tested in this example are sepsis or septic shock. The results of this example are disclosed as “The level of BM1 in the plasma or serum of patients suffering from sepsis, or septic shock was significantly higher than in the respective samples of patients not suffering from a sepsis condition” (pg. 33, lines 4-6).
Although the heading of example 3 states “Levels in healthy subjects with subjects at risk of suffering from sepsis”, no evidence is provided for using the measured biomarker levels for predicting the actual risk of suffering from sepsis. The subjects were either already suffering from sepsis or septic shock, or were control subjects.
Example 4: Comparing performance of BM1 to PCT. The example discloses the biomarker and PCT levels determined in Example 1. No risk prediction is disclosed.
Example 5: Bioanalytical characterization of BM1 as biomarker. The example discloses: (a) the biomarker levels in plasma and urine samples from septic patients and control patients (pg. 35, line 7) and (b) plasma samples of newborns (day 1 -10) without and with sepsis (pg. 35, line 15). No risk prediction was disclosed. The newborns were either with or without sepsis.
Example 6: ELISA for the detection of BM1. The example discloses ELISA test used for determining the biomarker levels.
Example 7: Internal Standard for HPLC-MS/MS. The example discloses use of isotopically labelled BM1 as internal standard.
All seven examples fail to disclose how methods of claims 1 and 13 can be used to predict actual risk of a sepsis condition because no data for risk calculations is provided.
Additionally, regarding claim 3 reciting “wherein the sepsis condition is any one or more of sepsis diseases selected from the group consisting of systemic inflammatory response syndrome (SIRS), sepsis, septic shock and multiple organ dysfunction syndrome (MODS)”, the specification provides data for only two sepsis conditions: sepsis and septic shock (see Example 3 discussion above). No data is disclosed for subjects with systemic inflammatory response syndrome and multiple organ dysfunction syndrome.
In summary, the originally filed specification lacks direction or guidance with regard to: (a) using the methods of claims 1 and 13 for predicting a risk of a sepsis condition and (b) applying the methods to subjects suffering from sepsis conditions other than sepsis and septic shock. Therefore, based on the above findings, one of ordinary skill in the art would conclude that Applicant did not have possession of the claimed invention.
Claims 2-4 and 7-9 are rejected because they depend from rejected claim 1.
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.
Claim 1-14 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.
Claims 1 and 13 recite “a method of predicting a sepsis condition in a subject” … “wherein an elevated biomarker level is indicative of the risk of the sepsis condition”. It is unclear how a sepsis condition can be predicted when the elevated biomarker level is indicative of the risk of the sepsis condition, but not the sepsis condition itself. The claim will be interpreted as a method of predicting a risk of a sepsis condition in a subject.
Claim 1 recites “the risk of the sepsis condition”. There is insufficient antecedent basis for “the risk”.
Claim 3 recites the sepsis condition is any one or more of sepsis diseases selected from the group consisting of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Both syndromes are not the forms or varieties of sepsis diseases. These are medical conditions that can be caused or triggered by sepsis, but there can also result from a number of other, sepsis unrelated, factors. Therefore, sepsis diseases cannot be selected from the group consisting of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome.
Claim 4 recites "such as" (in (i), (ii), and (iv)). This phrase renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 4 recites NMR spectroscopy. It is unclear how Applicant intends to use NMR for determining biomarker levels because NMR is not designed for quantitation purposes.
Claims 5, 6, and 14 recite “determining the level of” (in step a.). There is insufficient antecedent basis for “the level”.
Claim 7 recites the sample is body fluid selected from the group consisting of blood, plasma, serum, urine, faeces, sputum, synovial fluid, and saliva. Faeces is not a body fluid.
Claims 8 and 9 recite “preferably”. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 8 recites the biomarker comprising an isotopic label, which is the narrower statement of the internal standard compound. Claim 9 recites heavy isotopes C13, D, N15, O17 and O18, which further limit the atoms C, H, N, or O.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
For examination purposes, the claims will be interpreted as not requiring any of the features introduced by the term "preferably": an isotopic label (claim 8) and heavy isotopes C13, D, N15, O17 and O18 (claim 9).
Claim 10 recites “use of a diagnostic preparation in a method of determining a sepsis
condition”, claim 11 recites “use of an immunoagent specifically recognizing a biomarker”, and claim 12 recites “use of a compound of structure (I)” without setting forth any steps involved in the processes. Therefore, claims 10-12 are indefinite because they merely recite a use without any active, positive steps delimiting how this use is actually practiced (MPEP 2173.05(q)).
Claim 2 is rejected because it depends from rejected claim 1.
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 1-9 and 13-14 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring correlation, without significantly more.
Claims 1, 5, 6, and 13-14 recite methods of predicting or monitoring a sepsis condition in a subject. A method is a process, which is a statutory category of invention.
The claims recite methods of establishing a relationship between biomarker of structure (I) and a sepsis condition in a subject. This relationship is categorized as a naturally occurring correlation, and therefore it is a judicial exception.
The claims also recite steps of determining a level of a biomarker and comparing the determined level to a predetermined reference value of the biomarker. These additional steps of “determining” and “comparing” are an insignificant extra-solution activity that amounts to mere data gathering necessary to apply the judicial exception.
The claims do not recite any additional steps that would make the claims as a whole to integrate the recited judicial exception into a practical application of the exception. There are no additional elements recited in the claims adding to inventive concepts of the claims.
Claims 1, 5, 6, and 13-14 are not eligible under 35 U.S.C. 101.
Claims dependent from claim 1:
Claim 2 defines the reference level of the biomarker;
Claim 3 defines the sepsis condition and lists a group of sepsis-related diseases;
Claim 7 defines body fluids used for sampling.
Claims 2-3 and 7 do not recite any additional steps that would make the claims as a whole to amount to significantly more than the recited exception. There are no additional elements recited in the claims adding to inventive concept of the claims.
Claim 4 recites analytical methods for determining the biomarker level. These methods are recited at a high level of generality, as no method was specifically tailored to the biomarker of instant invention. Additionally, the recited methods are recognized as routine laboratory techniques and are considered insignificant extra-solution activities of data gathering. Therefore, the analytical methods individually or in combination with the judicial exception do not provide an inventive concept; so, the claim as a whole does not amount to significantly more than the judicial exception.
Claim 8 recites spiking an internal standard compound and claim 9 recites a detectable label. Spiking an internal standard compound and using a detectable label is part of determining a level of a biomarker and therefore, is an insignificant extra-solution activity that amounts to mere data gathering necessary to apply the judicial exception.
Claims 10-12 are rejected under 35 U.S.C. 101 because the claimed inventions are directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because a “use” is not a process, a machine, a manufacture, or a composition of matter. A “use” is not one of the statutory categories of invention.
For all these reasons, claims 1-14 are ineligible under 35 U.S.C. 101.
Subject Matter Free of the Prior Art
Claims 1-14 are free of the prior art.
The prior art neither teaches nor suggests a method of predicting a sepsis condition in a subject using the biomarker of structure (I) of instant invention.
The closest prior art:
Ivey et al. (WO 2004044554) teach diagnosis of sepsis or SIRS using biomarker profiles (see Table 14 for the list of biomarkers on pg. 67-71), but fail to teach the biomarker of structure (I) of instant invention;
Kellum et al. (U.S. Patent No. 10,533,989) teach N6-carbamoylthreonyl-adenosine as a significant metabolite between non-survivors and survivors of pneumonia and sepsis at 90 days (Table 3), but fail to teach predicting s sepsis condition in a subject;
Vold et al. (Cancer Res. 1982 Dec;42(12):5265-9) teach determining the biomarker level in urine samples of patients with lymphomas or solid tumors (Abstract), but fail to teach using the biomarker for predicting sepsis;
Zurita et al. (Molecules. 2018 May 8;23(5):1111) teach N6-focused structural modifications of adenosine-containing nucleosides as antiproliferative agents (Title and Abstract), but fail to teach using the biomarker of instant invention for predicting sepsis;
Singer (Curr Opin Pulm Med. 2013 May;19(3):305-9) teaches the following prognostic biomarkers of sepsis: IL-6, IL-10, NGAL, protein C, IL-1 receptor antagonist, and lactate (pg. 308, col. 1, Section “Prognostic biomarkers”), but fails to teach the biomarker of instant invention.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander Volkov whose telephone number is (571) 272-1899. The examiner can normally be reached M-F 9:00AM-5:00PM (EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached on (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEXANDER ALEXANDROVIC VOLKOV/Examiner, Art Unit 1677
/REBECCA M GIERE/Primary Examiner, Art Unit 1677