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 .
Election/Restrictions
Applicant's election with traverse of Group II (claims 11-14), a method of imaging cartilage by MRI, in the reply filed on May 4, 2026 is acknowledged. The traversal is on the ground that there is no undue burden on the examiner to consider all claims in the single application. This is not found persuasive because: (i) this application is a 371 of PCT/JP2021/039798 and for applications filed under 371, PCT rules for lack of unity apply, (ii) search burden is not required to show lack of unity, (iii) US 2010/0062478 A1 indicates a lack of special technical feature, indicating that the three groups of invention do not relate to a single general inventive concept (see Requirement for Restriction mailed April 13, 2026). Thus the lack of unity is deemed proper. Claims 10 and 15-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
The requirement is still deemed proper and is therefore made FINAL.
Status of Claims
Claims 10-18 are pending.
Claims 10 and 15-18 have been withdrawn from consideration.
Claims 11-14 are under examination.
Information Disclosure Statement
The information disclosure statement filed July 25, 2023 is acknowledged and has been considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 11-12 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Yoon (Yoon, H. J.; et al., Korean J. Radiol., 2014) in view of Zhu (Zhu, X. H.; et al., NMR Biomed., 2005).
Yoon teaches a method of using magnetic resonance imaging (MRI) to analyze cartilage tissue of the knee joint (pg. 123, Abstract). Yoon teaches imaging the cartilage first without a contrast agent, administering a Gd-DTPA contrast agent, and then acquiring more images (pg. 124, Image Acquisition). The images acquired and analyzed were T2-weighted images (pg. 124, T2 Measurement). Yoon teaches that the T2 values of several cartilage regions examined decreased when comparing pre-contrast and post-contrast average values (pg. 127, Table 1). Yoon teaches that using a Gd-based contrast agent in combination with pre-contrast and post-contrast T2 MRI analysis may be useful for the diagnosis of knee joint osteoarthritis (pg. 128, right column, second paragraph).
Yoon does not teach performing MRI with 17O-labeled water as a contrast agent.
Zhu teaches using 17O-labeled water for magnetic resonance imaging of brain tissue in vivo (pg. 83, Abstract). Zhu teaches that 17O is a stable isotope that can be detected by magnetic resonance instrumentation (pg. 83, right column, last paragraph). Zhu teaches that the concentration of 17O-labeled water can be quantitatively correlated to the proton T2 relaxation time in MRI and that the relaxation rate is linearly dependent on the 17O-labeled water concentration in biological solutions up to 5% enrichment (pg. 89, left column, second paragraph). Zhu uses these facts to suggest that 17O-labeled water can be used as a contrast agent by measuring the change in T2-weighted proton magnetic resonance signals (pg. 89, left column, second paragraph). Zhu teaches that 17O-labeled water can be used to effectively measure cerebral blood flow and cerebral metabolic rate of oxygen utilization in vivo through MRI (pg. 89, Figure 3; pg. 94, Figure 6).
A person of ordinary skill in the art would have recognized that both Yoon and Zhu teach methods of acquiring and analyzing MRI data using contrast agents and T2-weighted images. It would be understood that although Zhu discusses using 17O-labeled water as a contrast agent for imaging brain tissues, that this contrast agent would also be suitable for the use of imaging other tissues such as articular cartilage, as the contrast agent properties of 17O-labeled water are due to the composition of the material itself and not the body region in which it is used. It would thus be understood that 17O-labeled water and Gd-DTPA contrast agents may be substituted for one another in an MRI analysis.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of MRI analysis of knee cartilage using pre- and post-contrast T2-weighted imaged taught by Yoon with the 17O-labeled water contrast agent taught by Zhu through a simple substitution (MPEP § 2143(I)(B)). This would predictably result in an effective contrast agent-based MRI method capable of analyzing cartilage tissue.
Regarding claim 11, Yoon teaches a method of examining cartilage damage using signal values derived from MRI (pg. 123, Abstract). Yoon teaches acquiring images before and after administration of a Gd-DTPA contrast agent (pg. 124, Image Acquisition). Yoon teaches comparing the T2 signal values of different regions of interest obtained before and after administration of the contrast agent (pg. 127, Table 1). Yoon also teaches determining the difference in T2 signal values between pre- and post-contrast images (pg. 125, Statistical Analysis; and pg. 127, Table 2). Additionally, Zhu teaches 17O-labeled water is a suitable contrast agent (pg. 89, left column, second paragraph). Therefore, the combined teachings of Yoon and Zhu render claim 11 obvious.
Regarding claim 12, Yoon teaches a method of examining knee cartilage tissue using MRI (pg. 123, Abstract) and specifically characterizes the femoral articular cartilage (pg. 124, left column, first paragraph; and pg. 124, T2 Measurement). Therefore, the combined teachings of Yoon and Zhu render claim 12 obvious.
Regarding claim 14, Yoon teaches acquiring T2-weighted images before and after administration of a contrast agent using a 1.5 T Magnetom Avanto (Siemens Medical Solutions, Germany) instrument (pg. 124, Image Acquisition). Yoon also teaches that the T2 signal is reduced after the contrast agent has been administered (pg. 127, Table 1). Additionally, Zhu teaches that 17O-labeled water is useful for MRI analysis by proton T2 relaxation time (pg. 89, left column, second paragraph). Therefore, the combined teachings of Yoon and Zhu render claim 14 obvious.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Yoon and Zhu as applied to claims 11-12 and 14 above, and further in view of Hangaard (Hangaard, S.; et al., Acta Radiol., 2017).
As described above, Yoon teaches a method of using magnetic resonance imaging (MRI) to analyze cartilage tissue of the knee joint (pg. 123, Abstract). Yoon teaches imaging the cartilage first without a contrast agent, administering a Gd-DTPA contrast agent by intravenous injection, and then acquiring more images (pg. 124, Image Acquisition). Yoon teaches that using a Gd-based contrast agent in combination with pre-contrast and post-contrast T2 MRI analysis may be useful for the diagnosis of knee joint osteoarthritis (pg. 128, right column, second paragraph). Additionally, Zhu teaches using 17O-labeled water for magnetic resonance imaging of brain tissue in vivo (pg. 83, Abstract). Zhu teaches that 17O-labeled water can be used as a contrast agent by measuring the change in T2-weighted proton signals (pg. 89, left column, second paragraph).
The combination of Yoon and Zhu does not teach administering a contrast agent into a joint cavity of a subject.
Hangaard teaches MRI analysis of knee cartilage using a gadolinium-based contrast agent (pg. 336, Abstract). Hangaard teaches that the Gd-based contrast agent was administered via an intra-articular injection (pg. 337, MRI protocol, first paragraph). Hangaard teaches then acquiring MRI images of the cartilage (pg. 337, MRI protocol, second paragraph). Hangaard teaches that intra-articular administration of contrast media enables reducing the dose of the contrast agent given compared to that of the intravenous dose (pg. 339, left column, last paragraph).
A person of ordinary skill in the art would have recognized that Yoon, Zhu, and Hangaard all teach methods of contrast-based MRI analysis. It would also be recognized that Yoon and Hangaard both teach methods of imaging knee cartilage by gadolinium-based contrast agent-enhanced MRI analysis. It would be understood that Hangaard teaches an alternative means of administering the contrast agent, which is a simple substitution in protocol from the intravenous method taught by Yoon (MPEP § 2143(I)(B). It would also be recognized that the lower dose enabled by the intra-articular injection compared to intravenous administration reduces material used (decreasing cost) and may reduce systemic toxicities to the subject, thereby improving the method (MPEP § 2143(I)(C)). It would also be recognized that 17O-labeled water contrast agent could similarly be administered by this intraarticular injection method.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing data of the claimed invention to modify the 17O-labeled water-based MRI analysis of cartilage taught by Yoon and Zhu with the intra-articular administration of the contrast agent, as taught by Hangaard. This would predictably result in a similarly effective MRI method that reduces the amount of contrast agent administered due to administration of the contrast agent into the joint cavity of the knee. Therefore, the combined teachings of Yoon, Zhu, and Hangaard render claim 13 obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Eric P Mosher whose telephone number is (571)272-3258. The examiner can normally be reached Monday-Friday 9am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached at (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/E.P.M./Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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