DETAILED ACTION
Status of the Application
Claims 1-13 are pending.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election with traverse of Group I, claims 2-5, drawn to a method for determining fibrinogen in a sample using thrombin as coagulation activator, with added factor XIII and defined measurement conditions in a communication filed on 01/06/2026 is acknowledged.
Applicant’s election with traverse is on the grounds that claim 1 has not been included in any of the alleged groups of inventions. Claim 1 links inventions of Group I and Group II and is not included in the groups because it is a linking claim. Additionally, applicant states that Groups I and II should be examined together as they are in the same classification and Groups III and IV should be examined together as they are in the same classification. However, class/subclass is not the only criteria to show search burden. In addition, to class/subclass search, a comprehensive search of all the groups would require different keyword searches in the patent and non-patent literature that are not necessarily coextensive. There is no evidence of record indicating that each of the species in the Markush group is obvious over the others, or that they are not patentably distinct, such that prior art that could render one of the species unpatentable could be used to reject the other species under 35 USC 103.
The requirement is deemed proper and therefore is made FINAL.
Claims 6-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 01/06/2026.
Claims 1-5 are at issue and are being examined herein.
Priority
Acknowledgment is made of a claim for foreign priority under 35 U.S.C. 119(a)-(d) to EP22216869 filed 12/28/2022. Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/21/2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings submitted on 12/18/2023 have been reviewed and are accepted by the Examiner for examination purposes.
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 2 is 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 pre-AIA the applicant regards as the invention.
Claim 2 is indefinite in the recitation of “final concentration of added factor XIII in the reaction mixture corresponds to 5% to 200% of the norm”. There is no single concentration associated with the term “norm” as it relates to the concentration of factor XIII. The term is unclear in the absence of a specific concentration associated with “the norm”. The “norm” can be variable as what is the norm for one may not be the norm for another, and the norm can be different under different circumstances. It is impossible to determine if a final concentration is encompassed by the claim because it will depend on what is the concentration used as the norm. For examination purposes, no patentable weight will be given to the term “such that the final concentration…of the norm”. Correction is required.
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.
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 (i.e., changing from AIA to pre-AIA ) 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.
Claim(s) 1-5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Clauss (Acta Haematologica, 17, 237-246, 1957; cited in the IDS) in view of Mackie et al. (British Journal of Haematology, 121(3), 396-404, 2003), Theusinger et al. (Thrombosis and Haemostasis, 385-391, 2010; cited in the IDS), and Schubert et al. (US2009/0130645 A1, 05/21/2009).
Clauss teaches a method of determining fibrinogen concentration in a sample by diluting patient plasma samples (see pg. 241, Table 1), adding a reagent containing supraphysiologic thrombin (see pg. 239), measuring the clotting time and deriving the fibrinogen concentration from a calibration curve constructed with reference plasma (see pg. 238). Clauss does not teach the addition of factor XIII into the reaction mixture.
Mackie et al. teaches the Clauss assay requires a high degree of technical expertise if performed by manual methods, as the end-point is very difficult to determine at the higher dilutions of standard plasma, in test samples with low fibrinogen content, or in samples forming friable clots. Mechanical end-point techniques depend on the tensile strength of the clot (see pg. 398, column 1, Types of Fibrinogen Assay).
Theusinger et al. teaches the addition of factor XIII at supraphysiologic levels (approximate concentrations of 150 %, 300 % and 600 % of the normal range) increases maximum clot firmness (MCF), accelerates clot formation (CT) and increases clot stability (ML) in diluted samples assayed by ROTEM™ in patients with high fibrinogen and low factor XIII levels (see Summary and Table 2 & 3). Theusinger et al. does not teach a method for determining fibrinogen concentration.
Schubert et al. teaches addition of fibrinogen to blood samples and clot firmness is compared to reference values to determine factor XIII deficiencies (see pg. 4, paragraph [0049]). Schubert et al. teaches supplementing samples with factor XIII as a fibrin polymerization enhancer (see pg. 4, paragraphs [0049] - [0052]). Schubert et al. teaches that the factor XIII can be factor XIIIa (see pg. 4, paragraph [0050]). Schubert et al. teaches that common laboratory tests such as determination of fibrin concentration lack whether the tested components work properly under physiological conditions (see pg. 1, paragraph [0005]. Schubert et al. does not teach a method for determining fibrinogen concentration.
Claims 1-5 are directed to a method for determining fibrinogen in a sample comprising providing a reaction mixture of sample, wherein thrombin is the coagulation factor, measuring fibrin formation in the reaction mixture and additionally adding factor XIII, wherein the concentration of added factor XIII can be 5 % to 200 % of the norm and wherein the factor XIII can be isolated human factor XIII, recombinant factor XIII or wherein it is activated factor XIIIa.
It would have been obvious to one of ordinary skill in the art before the effective filling date of the claimed invention to modify the method of determining the concentration of fibrinogen of Clauss by adding factor XIII or activated factor XIIIa. A person of ordinary skill in the art is motivated to add factor XIII or activated factor XIIIa for the benefit of determining the low concentration of fibrinogen in diluted samples by enhancing clot formation and clot firmness because Mackie et al. teaches that conducting the Clauss method on diluted plasma samples that have low concentration of fibrinogen takes a high degree of expertise in determining the end-point measurement and the end-point technique depends on clot strength. In diluted samples, at low levels of fibrinogen, fibrinogen concentration is so low that insufficient or undetectable clot formation may occur. This represents the use of a known technique (factor XIII supplementation to enhance clot formation) to improve a similar method (a clot-based fibrinogen assay) in the same way, and applying a known technique to a known method ready for improvements to yield predictable results, as articulated in KSR and summarized in MPEP 2143. Additionally, a source of the recombinant factor XIII is not specified and can encompass any factor XIII including human factor XIII. It would be obvious to use human factor XIII because Schubert et al. uses factor XIII on human patient samples. One of ordinary skill in the art has a reasonable expectation of success at determining the fibrinogen concentration of a diluted sample by adding factor XIII or activated factor XIIIa because it would enhance clot formation and clot firmness as taught by Theusinger et al. and Schubert et al., extending the measurement range in the lower fibrinogen concentration range. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention.
Conclusion
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DALTON EDWARD KIEFER whose telephone number is (571)272-1235. The examiner can normally be reached M-F 7:30-5 EST.
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/DALTON EDWARD KIEFER/Examiner, Art Unit 1652
/DELIA M RAMIREZ/Primary Examiner, Art Unit 1652