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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on November 17, 2025 has been entered.
Status of Claims
Claims 1, 2, 9, 10, 13-16, 20, 23, 24 and 30-33 were pending. Claims 1, 2, 9, 10, 13-16, 20, 24 and 30-34 are canceled. Claims 34-39 are added.
Claims 23 and 34-39 are examined herein.
Withdrawn Rejections
The rejections of claims 1, 2, 9, 10, 13-16, 20, 24 and 30-34 are withdrawn in view of claims cancellation.
The rejections of claim 23 are withdrawn in view of claim amendments.
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 23 and 34-39 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.
Claim 23 recites MR-proADM level above 1.2 nmol/l and a range of MR-proADM levels between 1.2 to 1.45 nmol/l for selection of patients for hospitalization. The specification fails to disclose evidence that it is the patients with MR-proADM levels between 1.2 to 1.45 nmol/l that need hospitalization or that there were any patients participating in the study with MR-proADM levels in the range of 1.2 to 1.45 nmol/l.
Breadth of the claim - ranges of MR-proADM levels that are indicative of patients requiring hospitalization.
The invention is directed to a method for selecting patients for hospitalization based on MR-proADM levels.
State of the prior art & level of predictability in the art.
The art of biomarkers is highly unpredictable and one of ordinary skill in the art cannot deduce a narrower range of MR-proADM levels (e.g., 1.2 to 1.45 nmol/l) from the data disclosed as one large bin with levels above 1.2 nmol/l. The prior art does not support MR-proADM levels between 1.2 to 1.45 nmol/l.
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 discloses only one set of numeric data related to the clinical study (disclosed on pg. 32-35) – the table on pg. 34-35 show summary data for this study with measured proADM levels > 1.2 nmol/l (which is counted as MR-proADM levels in line with the Declaration #4). The only proADM levels listed in the table are above 1.2 nmol/l. There are no individual data for the claimed MR-proADM levels between 1.2 to 1.45 nmol/l and there are no data for other ranges. Applicant has no evidence to support the limitation of 1.2 to 1.45 range because it is not possible to conclude from the table that it was only patients falling in this range that required hospitalization, but not for example patients with levels outside this range.
Claims 34-39 are rejected as being dependent upon rejected claim 23.
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.
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 23 and 34-39 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 23 recites an MR-proADM cut-off level of 1.2 nmol/l and comparing the determined level to the cut-off level (lines 5-7). The last step of the method recites admitting the patient to hospital based with MR-proADM values between 1.2 to 1.45 nmol/l. 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).
For the purpose of compact prosecution and applying prior art under 35 U.S.C. 102 and 103, the instant claim is interpreted as requiring MR-proADM values above 1.2 nmol/l for patient hospitalization as presented in the table on pg. 34-35 of the specification.
Claim 23 recites the patient is suspected of having a respiratory infection, but is not diagnosed with a respiratory infection. The meaning of suspected of having a respiratory infection, but not diagnosed with a respiratory infection is unclear. First, diagnostic decisions made by general practitioners have some degree of uncertainty. Second, it is unclear where to draw a decision line between an undiagnosed suspected respiratory infection and a diagnosed condition that is probably a respiratory infection.
The metes and bounds of this limitation are unclear because: (a) the specification fails to provide a distinction between a suspected respiratory infection and a more definitive (non-suspected) respiratory infection; and how a suspected respiratory infection differs from a non-infectious respiratory condition; and (b) the art does not provide clear guidance for identifying patients meeting the limitations of suspected of having a respiratory infection, but not diagnosed with a respiratory infection.
The claim limitations fail to differentiate two important groups of patients: (a) having a respiratory condition because some medical conditions (e.g., allergy, a serious immune reaction, or a lung cancer) can exhibit respiratory-like symptoms and these conditions can be mistaken for a respiratory infection/condition and (b) having an infectious condition because some respiratory conditions are not infectious.
Claim 34 recites comprising frequent monitoring and/or critical care treatment. The metes and bounds of this limitation are unclear because the frequency of the monitoring is not defined by the claim or the specification and the nature of the critical care treatment is not recited in the claim.
Claim 35 recites further comprising determining at least one clinical score. The metes and bounds of this limitation are unclear because the least one specific clinical score is not recited in the claim and the specification does not disclose numerical parameters of clinical scores other than qSOFA score already recited in parent claim 23.
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 23 and 34-39 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature or a naturally occurring correlation, i.e., a correlation between a level of MR-proADM and a prognosis of disease progression without significantly more. This judicial exception is not integrated into a practical application because a naturally occurring correlation is generically linked to a hospitalization and a treatment. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because determining the level of MR-proADM is not an inventive concept.
Claims 23 and 34-39 are directed to a process, which is one of the four statutory categories. Claim 23 recites determining a level of MR-proADM in patients 18 years or older, suspected of having a respiratory infection, having a qSOFA score of 0 or 1, showing no clinical symptoms of a blood stream infection, a sepsis, a severe sepsis, and/or septic shock, not hospitalized, and the sample is obtained prior to clinical assessment in a hospital of said suspected respiratory infection, and is not diagnosed with a respiratory infection, a blood stream infection, a sepsis, a severe sepsis and/or septic shock, and admitting the patient having a determined MR-proADM level above 1.2 nmol/l in said sample to hospital. The cut-off value is interpreted as 1.2 nmol/l (see 112(b) rejection above for details).
Claim 23 also recites preparing a sample from a patient and determining a level of MR-proADM in said sample. Said limitations do not integrate the judicial exception into a practical application, because providing a patient sample and measuring levels of critical analytes are necessary steps for decision making. The naturally occurring correlation of claim 23 is only generally linked to a prognosis of disease progression and a need for hospitalization.
These above indicated limitations of determining an analyte level in a sample obtained from a patient and comparing the result to the level claimed in the instant invention is characterized as an abstract idea. In particular, such “comparing” steps amount to mental processes, namely concepts performed in the human mind, since comparing is considered an observation, evaluation, and/or a judgement.
Similar concepts involving comparing information regarding a sample or test subject to a control or target data have been held to be an "abstract mental process", as in University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 113 USPQ2d 1241 (Fed. Cir. 2014) which involved "comparing BRCA sequences and determining the existence of alterations", the collecting and comparing of known information in Classen, the comparing information regarding a sample or test subject to a control or target data in Ambry and Myriad CAFC, as well as Mayo (which also involved specific numerical cutoff levels).
Furthermore, claim 23 as a whole does not amount to significantly more than the judicial exception of a law of nature or a naturally occurring correlation. The concept of measuring MR-proADM level in blood samples of patients with infections and sepsis as a marker of mortality risk and severity is well-understood, routine, and convention (for examples, see Cicuendez et al. (IDS; Intensive Care Medicine Experimental, 2015) and Guignant et al. (IDS; Intensive Care Med. 2009)).
Claims 37-38 additionally recite steps of admitting a patient to hospital, and initiating treatment with an anti-infective agent based on the determined level of the at least one additional biomarker. However, the recited treatment with an anti-infective agent is a mere instruction of applying “an appropriate treatment” because claim 23 recites a suspected respiratory infection. No other claim recites steps of actually identifying/diagnosing the patient condition as an infection and determining its exact nature, such as, bacterial, viral, or fungal infection – the information required for selecting appropriate anti-infective agent.
Similarly, claims 34-36 and 39, which are dependent from claim 23, are rejected as failing to recite significantly more than the judicial exception of an abstract idea since each claim specifies decision steps that do not further integrate a law of nature or a naturally occurring correlation into a practical application beyond generally linking the concept to risk level of disease progression.
Therefore, claims 23 and 34-39 are ineligible under 35 U.S.C. 101.
Response to Arguments
Applicant's arguments filed November 17, 2025 have been fully considered.
Applicant argues about the rejections of cancelled claims 1, 2, 9, 10, 13-16, 20, 24, 26, 27, and 30-33. The argument is persuasive and the rejections of claims 1, 2, 9, 10, 13-16, 20, 24, 26, 27, and 30-33 are withdrawn.
Claim 23 was rejected under 112(a) because the specification fails to provide any evidence of measured MR-proADM concentrations and the example in the specification discloses only proADM levels (pg. 35). Applicant argues that “the "proADM" marker measured in the Examples was in fact MR-proADM” (Remarks, pg. 6, last par. and the Declaration par. 4). The argument is persuasive and the rejection of claim 23 under 112(a) is withdrawn.
Claim 23 was rejected under 112(b) because it is unclear why the presence of mild symptoms of a respiratory condition is sufficient to make a determination of an infectious nature of the condition. Applicant argues that “claim 23 no longer recites "mild symptoms of a respiratory condition" and this claim does not require a step of making a determination of an infectious nature of the condition” (pg. 7, par. 3). The argument is persuasive and the rejection of claim 23 under 112(b) based on the recitation of "mild symptoms of a respiratory condition" is withdrawn.
Applicant’s arguments about claims 1, 2, 9, 10, 13, 14, 20, 24, and 32-33 rejected under 35 U.S.C. § 103 (pg. 7, section 103 – pg. 9, par. 1) are moot because the rejections have been withdrawn.
Applicant’s arguments related to amended claim 23 are moot because the rejection of claim 23 under 35 U.S.C. § 103 has been withdrawn.
The Declaration of Aline Pehla is acknowledged.
Subject Matter Free of the Prior Art
Claims 23 and 34-39 are free of the prior art.
The prior art neither teaches nor suggests a method comprising determining a level of MR-proADM in the sample and admitting the patient having a determined MR-proADM level between 1.2 and 1.45 nmol/l in said sample to hospital.
The closest prior art of Albrich et al. (BMC Infectious Diseases, 2011, 11:112) teaches a cut-off MR-proADM level of 1.5 nmol/l for admission to hospital.
Conclusion
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/ALEXANDER ALEXANDROVIC VOLKOV/
Examiner, Art Unit 1677
/REBECCA M GIERE/Primary Examiner, Art Unit 1677