DETAILED ACTION
Applicant’s amendments submitted on 12/16/2025 and 1/20/2026 are acknowledged. Please note the amendment submitted 12/16/2025 was not entered and the amendment filed 1/20/2026 appears to include the amendment of 12/16/2025.
In the amendment submitted 12/16/2025, Claims 29, 32, 37-38, 51, 54-56, and 59 were amended. Claims 1-28, 30-31, 35, 39-40, 48-50, 53, and 57-58 were canceled. Claims 54-55 remained withdrawn pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention. Claims 29, 32-34, 36-38, 41-47, 51-52, 54-56, and 59 remained pending in the instant application.
In the amendment submitted 1/20/2026, Claim 29 is currently amended. Claims 1-28, 30-31, 35, 39-40, 48-50, 53, and 57-58 remain canceled. Claims 54-55 remain withdrawn pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention. Claims 29, 32-34, 36-38, 41-47, 51-52, 54-56, and 59 remain pending in the instant application.
Claims 29, 32-34, 36-38, 41-47, 51-52, 56, and 59 are the subject of this office 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1/20/2026 has been entered.
Priority
The instant application is a U.S. National Phase of PCT/SE2020/050448, filed on 5/5/2020, and claims Domestic Benefit to U.S. Provisional Application Serial No. 62/843,652, filed on 5/6/2019.
Response to Amendment
Applicant’s amendment to the specification submitted 12/16/2025 overcomes the objection previously set forth in the Final Rejection mailed on 9/18/2025.
Applicant’s deletion of the limitation “or a fragment thereof” from the claims overcomes the 35 U.S.C. 112(a) written description rejection previously set forth in the Final Rejection mailed on 9/18/2025. Accordingly, the rejection is withdrawn.
Applicant’s cancelation of claim 53 renders moot the 35 U.S.C. 112(d) rejection previously set forth in the Final Rejection mailed on 9/18/2025. Accordingly, the rejection is withdrawn.
Applicant’s amendment to claim 29 to recite “selecting a treatment adapted for combating M. pneumoniae infections for the human subject with the respiratory infection classified as Mycoplasma pneumonia caused by M. pneumoniae, wherein the selected treatment is an antibiotic targeting the bacterial rRNA in ribosomal complexes, and administering the selected treatment to the human subject” overcomes the 35 U.S.C. 101 rejection previously set forth in the Final Rejection mailed on 9/18/2025. Accordingly, the rejection is withdrawn.
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.
Claims 29, 32-34, 36-38, 41-47, 51-52, 56, and 59 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 enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
In making a determination that a disclosure does not satisfy the enablement requirement, the factors that may be considered include: (A) the breadth of the claims, (B) the nature of the invention, (C) the state of the prior art, (D) the level of one of ordinary skill, (E) the level of predictability in the art, (F) the amount of direction provided by the inventor, (G) the existence of working examples, and (H) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. While it is not essential that every factor be examined in detail, those factors deemed most relevant should be considered.
Nature of the invention. The claims are drawn to a method of analysis in which a human subject having a respiratory infection suspected of being Mycoplasma pneumonia is classified as having a Mycoplasma pneumonia respiratory infection caused by Mycoplasma pneumoniae. In order to classify the human subject as having a Mycoplasma pneumonia respiratory infection caused by Mycoplasma pneumoniae, a concentration of thymidine kinase 1 (TK1) material is determined in a body sample from the human subject by contacting the body sample with an anti-TK1 antibody as claimed, and comparing the determined concentration of TK1 material in the body sample with a threshold value. The respiratory infection is classified as a Mycoplasma pneumonia respiratory infection caused by Mycoplasma pneumoniae if the concentration of TK1 in the body sample exceeds the threshold value and an antibiotic treatment that targets the bacterial rRNA in ribosomal complexes is administered to the human subject.
Breadth of the claims. A body sample from a human subject is recited at a high level of generality and embraces any type of sample that can be obtained from a human body. A threshold value is recited at a high level of generality and is not objectively limited to a specific, determined value in the claims. The treatment embraces administering an antibiotic targeting the bacterial rRNA in ribosomal complexes. The anti-TK1 antibody is selected from the group consisting of:
a monoclonal anti-TK1 antibody having specificity for the epitope consisting of SEQ ID NO: 1 and having a variable heavy (VH) domain complementarity determining region 1 (CDR1) comprising amino acid sequence SEQ ID NO: 5; a VH domain CDR2 comprising amino acid sequence SEQ ID NO: 6; a VH domain CDR3 comprising amino acid sequence SEQ ID NO: 7; a variable light (VL) domain CDR1 comprising amino acid sequence SEQ ID NO: 8; a VL domain CDR2 comprising amino acid sequence SEQ ID NO: 9; and a VL domain CDR3 comprising amino acid sequence SEQ ID NO: 10;
a monoclonal anti-TK1 antibody having specificity for the epitopes SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO: 4 and having a VH domain CDR1 comprising amino acid sequence SEQ ID NO: 5; a VH domain CDR2 comprising amino acid sequence SEQ ID NO: 17; a VH domain CDR3 comprising amino acid sequence SEQ ID NO: 18; a VL domain CDR1 comprising amino acid sequence SEQ ID NO: 19; a VL domain CDR2 comprising amino acid sequence SEQ ID NO: 9; and a VL domain CDR3 comprising amino acid sequence SEQ ID NO: 10; and
a monoclonal anti-TK1 antibody having specificity for a conformation dependent epitope of TK1 and having a VH domain CDR1 comprising amino acid sequence SEQ ID NO: 11; a VH domain CDR2 comprising amino acid sequence SEQ ID NO: 12; a VH domain CDR3 comprising amino acid sequence SEQ ID NO: 13; a VL domain CDR1 comprising amino acid sequence SEQ ID NO: 14; a VL domain CDR2 comprising amino acid sequence SEQ ID NO: 15; and a VL domain CDR3 comprising amino acid sequence SEQ ID NO: 16.
State of the prior art and predictability of the art. The state of the art at the time of the invention demonstrates an interest in thymidine kinase 1 as a biomarker for lung cancer. Furthermore, TK1 values were known to be significantly higher in individuals with lung diseases, including cancer.
Holdenrieder et al. (Anticancer Res., 2010, Vol. 30, pp.1855-1862) disclose that thymidine kinase indicates the proliferative characteristics of neoplastic cells and is present in most living cells (see p.1856, paragraph bridging left and right columns). Holdenrieder et al. describe that the TK1 isoform is most relevant for detection and estimation of prognosis in cancer and can be measured by radio or enzyme-immunological techniques (see p.1856, right column, 1st paragraph). TK1 has been previously been shown to be useful for the estimation of prognosis in patients with non-Hodgkin’s lymphoma and plasmocytoma. Holdenrieder et al. sought to examine the diagnostic capacity of TK1 for lung cancer versus differential diagnostically relevant lung diseases and how they compare to various non-lung diseases. A total of 294 patients were included in Holdenrieder et al.’s study—181 patients with inoperable lung cancer, 40 patients with benign lung diseases, 44 patients with non-lung diseases, and 29 healthy control patients (see p.1856, right column, 2nd passage). Patients with benign lung diseases included those with pneumonia, tuberculosis, and respiratory insufficiency, and patients with non-lung diseases included those with bacterial infections. TK1 levels were determined in blood sera samples taken from the patients (see p.1857, left column, 4th paragraph). Holdenrieder et al. report that healthy individuals had low TK1 values, while patients with lung cancer had significantly higher values (see p.1857, right column, 1st passage). However, TK1 levels of individuals suffering from benign lung diseases and benign non-lung diseases were often elevated. Moreover, there was no significant difference between the TK1 level in patients with lung cancer and patients with benign lung diseases (see p.1857, right column, last paragraph, Table 1, and Figs. 1-2). Moreover, patients with benign non-lung diseases had significantly higher TK1 levels in serum of patients with acute infections as compared to healthy controls (see p.1858, paragraph bridging left and right columns and Fig. 2). Holdenrieder et al. conclude that although TK1 levels in healthy individuals are very low, while patients with lung cancer had significantly higher values, patients with benign lung diseases also had considerably elevated TK1 levels—limiting the diagnostic value of TK1 (see p.1860, right column, 1st paragraph). Holdenrieder et al. attribute this finding to infectious, granulomatous or allergic disease being massive stimuli for the proliferation of immune cells to fight against abnormal condition, thereby resulting in TK1 being produced and released at higher frequency and amounts in these disorders, which has been previously demonstrated in the prior art. Therefore, Holdenrieder et al. demonstrate that TK1 cannot be used as a biomarker to distinguish lung diseases from each other, since all lung diseases—and even benign non-lung diseases—result in significantly elevated TK1 levels that are not significantly distinguishable from each other as compared to healthy controls.
Guidance in the specification. The guidance provided in the specification does not significantly improve the results demonstrated in the prior art. Furthermore, the results disclosed in the specification largely mirror those that were demonstrated in the prior art at the time of the invention. Specifically, Applicant only demonstrates serum samples as body samples for detecting a concentration of TK1 in (see Figs. 1-9 and Examples 1-2). Human subjects with acute infection were examined for grounds of bacterial infection or viral infection (see p.22, 3rd passage). Examination included symptoms of fevers of at least 38°C, CRP, white blood cell counts, X-ray findings, and in some cases microbiological test results (see p.22, 4th passage). Known chronic viral infections were excluded from the experiments. TK1 levels were measured in serum samples from patients with respiratory infection utilizing the AroCell TK 210 ELISA procedure, which utilizes biotinylated anti-TK1 antibodies as claimed.
The results of the procedure demonstrated that TK1 levels in serum from patients with bacterial, viral, and Mycoplasma pneumoniae infection were elevated compared to healthy controls (see Fig. 1 reproduced below). However, as can be seen in the reproduced figure, TK1 levels largely overlap in the bacterial, viral and Mycoplasma subsets, with samples from the bacterial and viral subsets even showing higher levels of TK1 than the Mycoplasma subset.
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When patient groups were limited to patients with upper respiratory tract infections caused by bacteria or M. pneumoniae, a large amount of overlap in TK1 levels were still observed (see Fig. 2 reproduced below).
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Serum TK1 was also assessed in patients with lower respiratory tract infections in patients with bacterial pneumonia and Mycoplasma pneumonia. Similarly, patients with bacterial and Mycoplasma pneumonia reflected higher serum TK1 levels overall as compared to healthy controls. However, between bacterial and Mycoplasma pneumonia patients, serum TK1 levels largely overlap with several patients with bacterial pneumonia having higher levels of TK1 than patients with Mycoplasma pneumonia (see Fig. 9A reproduced below).
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Therefore, the results reflected in the disclosure examples reflect what was observed in the state of the art at the time of the invention. Namely, TK1 levels are elevated in patients with bacterial, viral, and Mycoplasma infected patients as compared to healthy controls, with great overlap in these subgroups. Moreover, there remains to be difficulty in differentiating the cause of infection from assessing serum TK1 levels alone due to the substantial overlaps in TK1 levels among bacterial, viral, and Mycoplasma infection.
Amount of experimentation necessary. In view of the foregoing analysis, one of skill in the art would not be able to practice the claimed invention without performing undue experimentation, and would have no reasonable expectation of achieving success of classifying respiratory infections as caused by Mycoplasma pneumoniae due to the significant overlap in TK1 levels across infections caused by bacteria and viruses.
Taking these factors into account, undue experimentation would be required by one of ordinary skill in the art to practice the claimed invention. Thus, the claims are not enabled by the disclosure.
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.
Claims 29, 32-34, 36-38, 41-47, 51-52, 56, and 59 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 29 recites the limitation "the bacterial rRNA in ribosomal complexes" in lines 14-15. There is insufficient antecedent basis for this limitation in the claim. Claim 29 recites and sets forth Mycoplasma pneumoniae, but it is not clear if “the bacterial rRNA” is intended to refer specifically to M. pneumoniae rRNA in the ribosomal complexes or more broadly to any bacterial rRNA in the ribosomal complex. Consequently, one of ordinary skill in the art would not be able to determine the metes and bounds of the claim limitation. Thus, claim 29 is indefinite.
Claims 32-34, 36-38, 41-47, 51-52, 56, and 59 are also rejected for being dependent on a rejected base claim and failing to remedy the issue set forth above.
Claim 38 recites “determining the concentration of TK1 material in the body sample based on the determined amount of bound anti-TK1 antibody and a standard correlation between an amount of bound anti-TK1 antibody and a predefined concentration of TK1 material” in lines 5-7. The recitation of “an amount of bound anti-TK1 antibody” renders the claim indefinite because it is not clear if this limitation is intended to refer to “the determined amount of bound anti-TK1 antibody” or to a separate and distinct amount of bound anti-TK1 antibody. The relation of the determined amount of bound anti-TK1 antibody and the standard correlation to determine the concentration of TK1 is not made clear. Thus a person of ordinary skill in the art would not be able to determine the metes and bounds of the claimed invention, and claim 38 is indefinite.
Response to Arguments
Applicant’s arguments with respect to claims 29, 32-34, 36-38, 41-47, 51-52, 56, and 59 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Upon further consideration of the claimed invention and state of the art at the time of the invention, the claimed invention fails to comply with the enablement requirement for the reasons set forth above. In summary, the state of the art observed that serum TK1 levels are broadly useful for determining a state of infection but cannot differentiate certain infections from each other (e.g., bacterial, viral, cancer, etc.). Accordingly, the 35 U.S.C. 103 rejection of claims 29, 32-34, 36-38, 41-47, 51-52, 56, and 59 has been withdrawn and the claims are rejected under 35 U.S.C. 112(a).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN PAUL SELWANES whose telephone number is (571)272-9346. The examiner can normally be reached Mon-Fri 7:30-5:00.
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/J.P.S./Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651