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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 07 August 2025 has been entered.
Response to Amendment
Applicant’s response filed 07 August 2025 has been received and entered. Claim 17-18, 25, 34, 36 and 40-47 have been amended and claims 1-16, 19-20, 22-24, 26, 29-33, 49, 52 and 55 have been canceled. Claims 17-18, 21, 25, 27-28, 34-48, 50-51, 53-54 and 56-57 are currently pending in the instant Office action.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Any objection or rejection of record which is not expressly repeated in this action has been overcome by Applicant’s response and withdrawn.
Applicant’s arguments filed 24 February 2025 have been fully considered but are not deemed to be persuasive.
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 17-18, 21, 25, 27-28, 34-48, 50-51, 53-54 and 56-57 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 17, 18, 34 and 36 have been amended to recite “wherein, at the time the bodily fluid obtained from the subject, the subject had received diuretics as a therapy for said acute heart failure, the subject was not diagnosed as suffering from residual congestion, and the subject was suffering from residual congestion”. Claims 21, 25, 27-28, 35, 37-48, 50-51, 53-54 and 56-57 are dependent on claims which include this limitation.
The claims are internally inconsistent. In order to execute the claimed method, one would need to know if the subject was suffering from residual congestion but the claims also require that the subject not be diagnosed as suffering from residual congestion. The claims are indefinite and unclear because one or ordinary skill in the art can’t know if they are preparing a sample which reads on the instant claims or not because the subject is not diagnosed with residual congestion but they are suffering from residual congestion which one would only know if there is a diagnosis. The claims are circular and internally inconsistent and therefore, unclear and indefinite.
Response to Arguments
Applicant argues at page 9 of the response (based on comments from the Advisory action mailed 21 July 2025) that:
This issue appears to be concerned with asserting infringement more than with enablement. Enablement does not require a priori knowledge that one is infringing a claim or not. Enablement only requires that one skilled in the are is capable of performing the claimed method which in this case merely requires preparing a sample by providing bodily fluid. This is well within the capability of one skilled in the art.
While it is true that the nature of the sample prepared will ultimately determine whether or not the claim is infringed and that the person practicing the method might not have knowledge of whether they are infringing the claim or not as they begin practicing the method, this is simply not a relevant concern for enablement or patentability at all.
Applicant’s argument has been fully considered, but is not found persuasive. Applicant is referred to MPEP § 2173:
It is of utmost importance that patents issue with definite claims that clearly and precisely inform persons skilled in the art of the boundaries of protected subject matter.
The primary purpose of this requirement of definiteness of claim language is to ensure that the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent. A secondary purpose is to provide a clear measure of what the inventor or a joint inventor regards as the invention so that it can be determined whether the claimed invention meets all the criteria for patentability and whether the specification meets the criteria of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph with respect to the claimed invention.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 17, 18, 21, 25, 27-28, 34-48, 50-51, 53-54 and 56-57 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bergmann et al. (WO 2014/147153A1) in view of Ambrosy et al. (Eur. Heart J. 34: 835-843, 2013) and in light of Gheorghiade et al. (Eur. J. Heart Failure 12: 423-433, 2010) and Felker et al. (Circ. Heart Fail. 2009; 2: 56-62).
Bergmann et al. (‘153) teach a method of preparing a sample from a patient who has been diagnosed with acute heart failure (Example 8 at page 34) comprising a bodily fluid and a binder that binds to pro-adrenomedullin of at least 5 amino acids (see page 6) wherein the level of pro-adrenomedullin is above 50 pg/ml for ADM-NH2, 0.5nmol/L for MR-proADM and 85 pmol/L for CT-proADM. Because the patients have heart failure and Bergmann et al. teach that ADM levels for patients with heart failure are above the recited thresholds, the method of Bergmann et al. to prepare the samples would necessarily have the levels recited in the instant claims, absent evidence to the contrary. Newly added claims 40-47 recite that the ADM values are 70, 90 or 100 pg/ml, however, as Bergmann et al. already teach a level above 50 pg/ml, any and all levels above such threshold level would also be obvious as they would indicate a greater severity of the condition. Additionally, Bergmann et al. specifically state that the threshold for plasm ADM is 70 or 90 pg/ml (see page 12, lines 2-4). Bergmann et al. teach that the assay used in the disclosed method can be an immunoassay in any of a variety of formats (see page 9, lines 5-8) as well as specifically exemplifying a sandwhich assay (see Example 2). Bergmann et al. also teaches calibration of the ADM assay using commercially available control samples (see page 11 (lines28-29). Bergmann et al. teaches preparing the sample at admission to a hospital and monitoring to evaluate the response to therapeutic measures taken (see page 30, last paragraph). While Bergmann et al. does not explicitly state to prepare a second sample from a patient, the teaching of preparing the sample at admission to the hospital and monitoring to evaluate the response to therapeutic measures taken implicitly instructs that additional sampling and preparing samples would necessarily occur because measuring ADM levels is used to evaluate subjects with heart failure (claim 28).
Claim 17 recites that the subject from whom the bodily fluid is obtained has been treated for the diagnosed condition recited in the claim. However, the subjects from Bergmann et al. (‘153) were subjects in a hospital setting who were diagnosed for heart failure. It necessarily follows that a subject being seen in a hospital setting for heart failure were diagnosed for the condition and would be appropriately treated for that condition. The claims have been amended to recite that the subject had received diuretics as therapy for said acute heart failure. While Bergmann (‘153) does not specifically state that diuretics were administered, diuretics and specifically loop diuretics are the foundation of acute decompensated heart failure and 90% of patients hospitalized with acute heart failure in the US receive IV loop diuretics during hospitalization as evidenced by Felker et al. (Circ. Heart Fail. 2009; 2: 56-62). Therefore, it would have been obvious to prepare a sample from a subject diagnosed with acute heart failure and who had received diuretics as therapy because most (90%) of subjects with acute heart failure are treated in this manner. Additionally, it would have been obvious to make additional samples while the subjects were in the hospital setting, including after said subjects had been treated for heart failure in order to assess the health status of the subjects. Claim 17 also recites that “at the time the bodily fluid obtained from the subject, the subject is not identified as suffering from residual congestion”. The cited reference is silent as to the subjects being identified as suffering from residual congestion. However, as the methods of the cited references utilize measurement of ADM for evaluating the status of the patients, such samples would be prepared to evaluate the subjects and would necessarily include those subjects identified and not identified as suffering from residual congestion. It is reasonable to expect samples which contain levels of ADM in the range that is recited in the claims because subjects with heart failure have levels of ADM as recited in the claims.
The teachings of Bergmann et al. (‘153) are provided above. Bergmann et al. (‘153) does not teach providing a congestion score or stratifying subjects into groups of grades of congestion or selection of a subject who has been treated for congestion.
Ambrosy et al. teach that signs and symptoms of congestion are the most common cause for hospitalization for heart failure. Ambrosy et al. provide a grading scale for assessing signs and symptoms of congestion (i.e. clinical surrogates) which include orthopnoea, jugular venous distension and oedema (see Table 1 at page 837) as well as creating a composite congestion score (Figure 1) (claim 36) to evaluate patients suffering from heart failure. Ambrosy et al. also disclose stratifying subjects into groups of grades of congestion (see page 839, paragraph 2 (responders, partial-responders and non-responders) and Tables 3-4). Ambrosy et al. teach that subjects who are admitted for heart failure are administered interventions or therapy for the heart failure and congestion which drove the patients to the hospital (see page 837, column 2, final paragraph “clinical congestion improved rapidly and dramatically in response to standard therapy”). While Ambrosy et al. does not define “standard therapy”, Gheorghiade et al. teach that therapy for congestion in heart failure is directed to removing excess intravascular and extravascular fluid and includes diuretics, ultrafiltration, vasopressin antagonists, adenosine antagonists, beta-blockers, ACE inhibitors, aldosterone receptor antagonists and cardiac resynchronization therapy (see paragraph spanning pages 424-425). Ambrosy et al. suggest that assessing and grading congestion during hospitalization and pre-discharge should be employed to guide therapy and discharge decision making (see page 842, column 1, paragraph 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to include steps of providing a congestion score (claims 17-18, 36-38) and stratifying subjects into groups of grades of congestion (claim 21, 36-38) to the method of preparing a sample of Bergmann et al. (‘153) because the method is evaluating a sample from subjects with heart failure and the steps taught by Ambrosy et al. are applicable when treating/assessing an individual with heart failure. It also would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to prepare a sample from a subject who had received diuretics and was treated for congestion (claim 39) because administration of diuretics is the standard of care for acute heart failure as evidenced by Felker et al. and subjects with heart failure are usually suffering from congestion and the subjects would have been treated for congestion as it is a therapy for heart failure. One of ordinary skill in the art would be motivated to include the various additional steps taught by Ambrosy et al. because Ambrosy teach that such steps would assist in guiding therapy, such as diuretics. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent evidence to the contrary.
With regard to claims 36-38 which recite specific congestion scores, while the prior art does not specifically identify such subjects, if the subjects who were sampled in the references were assigned congestion scores, it would be expected that they would have varying congestion scores consistent with the claims, absent evidence to the contrary.
With regard to claims 40-47 which recite specific threshold values for mature ADM-NH2, in the process of preparing a sample from a subject wherein the subject has been diagnosed with acute heart failure or chronic heart failure with worsening signs/symptoms of chronic heart failure and has been treated for the diagnosed condition, subjects will have various levels of mature ADM-NH2 as adrenomedullin is a protein that is elevated in subjects with heart failure (as evidenced by Bergmann et al). As it is obvious to measure this protein in such patients, it is obvious to prepare a sample comprising bodily fluid and an antibody (binder) to mature ADM-NH2. Because the level of the protein is elevated in such patients, it would be obvious to obtain a sample in which the level of the protein is above a given threshold because this is a natural phenomenon and therefore, preparing a sample wherein the level of mature ADM-NH2 is above a predetermined threshold is prima facie obvious.
Response to Arguments
Applicant argues at page 10 of the response the claims have been amended to recite "wherein, at the time the bodily fluid obtained from the subject,
the subject had received diuretics as a therapy for said acute heart failure, the subject was not diagnosed as suffering from residual congestion, and the subject was suffering from residual congestion."
Applicant argues that there is no teaching in any of the cited prior art that the subjects are suffering from residual congestion or any evidence or reason for one skilled in the art to reasonably think that the subjects are suffering from undiagnosed residual congestion. Applicant also asserts that the claims also require that the subject had received diuretics as a therapy for said acute heart failure and argues that there is no evidence or basis for one skilled in the art to think that the subject of the prior art has received diuretics as a therapy for said acute heart failure as the primary references fails to even mention the word diuretic in its disclosure. Applicant argues that the rejection requires upon a theory of inherency which requires a reasonable scientific basis to assume these claim requirements are present in the prior art.
Applicant’s arguments have been fully considered, but are not found persuasive. With regard to whether or not the subjects had received diuretics as a therapy for acute heart failure, the art teaches that 90% of subjects with acute heart failure are treated with diuretics, as evidenced by Felker et al. So, while Bergman may not teach that diuretics are a therapy that the subjects are receiving, it is standard of care for subjects with acute heart failure to be treated with diuretics as 90% of subjects with acute heart failure receive diuretics according to Felker et al.
The prior art of record clearly teaches a method of preparing a sample which comprises a bodily fluid and a binder as recited in the claims in a subject who has been diagnosed with the conditions recited in the claims as outlined above. The claims require the prepared sample to have a level of pro-adrenomedullin above 50 pg/ml and such a sample is obvious over the prior art of Bergmann et al. because such levels are consistent with levels of pro-adrenomedullin in subjects with the conditions recited in the claims as taught by Bergmann et al. Therefore, in the course of practicing the method of Bergmann et al., one of ordinary skill would arrive at a sample with the claimed characteristics (having a level of mature ADM-NH2 with a particular concentration) because there is motivation to sample such patients and to measure mature ADM-NH2 and because mature ADM-NH2 is elevated in the patient population being sampled, the particular values which are claimed would necessarily be achieved. With regard to whether or not the subjects are suffering from residual congestion but are not diagnosed with residual congestion, such a population of subjects are obvious over the cited references provided above. As it is obvious to practice the method as currently claimed, there will be subjects which may still suffer from residual congestion even though they are not diagnosed. There is clearly no way to select for these subjects because they are not diagnosed (note 112(b) rejection above for indefiniteness). However, it is still obvious to measure levels of mature ADM in subjects with acute heart failure who have been treated with diuretics (standard therapy for acute heart failure) and who have not been diagnosed with residual congestion but who are suffering with residual congestion. The process of measuring mature ADM is useful as taught by Bergman for monitoring and evaluating subjects being treated for acute heart failure.
Applicant argues at pages 10-11 of the response that Rubio-Gracia (cited exhibit) teach that about 75% of patients who are treated in a hospital setting for acute heart failure with diuretics still had mild or significant congestion after 7 days of treatment and that residual congestion is described in the introduction of the reference. Applicant asserts that congestion and residual congestion are “two separate and distinct things” and a teaching related to acute heart failure patients having congestion should not be conflated with an acute heart failure patient having residual congestion as these are not the same thing.
Applicant’s argument has been fully considered but are not found persuasive. Congestion and residual congestion are not so different as Applicant is asserting. Residual congestion is a term of the art that refers to congestion that remains after a subject has been treated for congestion. It is not a different condition or disorder from congestion but rather, it merely refers to the presence of congestion after a subject has been treated for congestion. The teachings of Rubio-Garcia et al. support the assertion that method of Bergman et al. which prepares a sample from a patient who has been diagnosed with acute heart failure at admission to a hospital and monitoring to evaluate the response to therapeutic measures taken would inherently include subjects who would be suffering from residual congestion even after treatment with diuretics. As pointed out above, 90% of subjects with acute heart failure receive diuretics in the hospital (Felker et al.) and 75% of subjects with acute heart failure who have been treated with diuretics have residual congestion (Rubio Grazia et al.). Therefore, it is reasonable to presume that the alleged missing portion of the prima facie case inherently/always/necessarily is present, contrary to Applicant’s assertion.
Applicant argues at page 11 of the response that the patients in the Bergman reference do not appear to have received any diuretic therapy. Applicant’s argument has been fully considered, but is not found persuasive. The subjects from Bergmann et al. (‘153) were subjects in a hospital setting who were diagnosed for heart failure. It necessarily follows that a subject being seen in a hospital setting for heart failure were diagnosed for the condition and would be appropriately treated for that condition. The claims have been amended to recite that the subject had received diuretics as therapy for said acute heart failure. While Bergman (‘153) does not specifically state that diuretics were administered, diuretics and specifically loop diuretics are the foundation of acute decompensated heart failure and 90% of patients hospitalized with acute heart failure in the US receive IV loop diuretics during hospitalization as evidenced by Felker et al. (Circ. Heart Fail. 2009; 2: 56-62). Therefore, even if Bergman does not specifically recite that the patients received diuretics, since 90% of patients with acute heart failure are treated with diuretics in a hospital setting as it is the standard of care for such a condition, one of ordinary skill in the art would conclude that the patients of Bergman et al. were so treated.
Applicant asserts at page 11 that there is an enormous unmet need for a more accurate and reliable marker for congestion that allows the physician to make objective and optimal decisions regarding adequate decongestion and the timing of the patients discharge from the hospital and that the claims of the current application meet this unmet need. Applicant’s argument has been fully considered, but is not found persuasive. The instant claims are not directed to a marker for congestion or a method of diagnosing congestion. The methods are directed to preparation of a sample by combining bodily fluid from a subject with acute heart failure who has been treated for the condition, which includes diuretics and wherein the subject has not been diagnosed with residual congestion but was suffering from residual congestion and wherein the level of mature ADM is above 50 pg/ml. The claims are obvious over the cited prior art for the reasons provided above. The source of the bodily fluid, patients with acute heart failure, who have received treatment (diuretics) and have mature ADM levels above 50 pg/ml are taught by Bergman et al. The claim requires that the patients are diagnosed with residual congestion but also be suffering from residual congestion at the time the bodily fluid is obtained. As pointed out above, this claim limitation is internally inconsistent because one cannot determine if they are suffering from residual congestion if they haven’t been diagnosed and the skilled artisan would not know the metes and bounds of the claim because they would not be able to identify the subject from whom to take the bodily sample in order to arrive practice the claimed method. However, in the course of practicing the method of Bergman et al., one of ordinary skill in the art would reasonably conclude that bodily fluid would have been obtained from subjects who were suffering from residual congestion whether or not they were diagnosed because Rubio-Gracia et al. state that 75% of patients who are treated for acute heart failure with diuretics still have residual congestion after 7 days of hospitalization and treatment. Therefore, the method of Bergman et al. would inherently prepare a sample from such subjects.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christine J Saoud whose telephone number is (571)272-0891. The examiner can normally be reached M-F, 6am-2:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dan Kolker, can be reached on 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Christine J Saoud/Primary Examiner, Art Unit 1647