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 .
Response to Arguments
Applicant’s arguments filed 02/16/2026 with respect to claims 1-3, 13-22, 24-29, 41, 50-55 have been considered but are not persuasive.
Applicant argues on pages 3-4
“In Example 1 above, the Applicant filed a declaration under 37 C.F.R. § 1.130(a)
affirming that the named inventor is the sole inventor of the subject matter disclosed in the article and that the co-author was a graduate student working under her direction and supervision and did not contribute to the conception of the claimed invention. According to Example 1, this was sufficient to show that the declaration established that the co-author was not a joint inventor…
For at least the foregoing reasons, Applicant submits that (1) the Office erred
when it asserted that the Thakor Declaration is insufficient to overcome the rejections under § 103; (2) Razavi is not available as art against the pending claims; and (3) for reasons of record, all § 103 rejections that include reliance on Razavi should be withdrawn by the Office for being deficient.”
Examiner respectfully disagrees for the following reasons. Firstly, the example affidavit provided in the MPEP specifically recites “the named inventor is the sole inventor of the subject matter disclosed”. This statement is not present in the affidavit presented by the inventor. The recitation of “my work” as in the presented affidavit cannot be equated as sole inventor (e.g. my work only). Hence the affidavit is not similar to the example in MPEP. Secondly, applicant admits that others have contributed to the work in Razavi, but fails to identify what work was contributed. There is lot of overlapping subject matter between the application disclosure (MPEP 2138.04 defines “conception” as disclosure), and the reference Razavi. In view of applicants admission, it can be inferred that some parts of Razavi were not contributed by the inventor, and hence affidavit does not explicitly make certain what is the inventors work and what is not. Thirdly, the examiner identified only one particular claim element, i.e. ISAPA of 272 W/cm2, (subject matter X of example 1 noted by applicant) that is deficient in Burks and, the second reference Razavi is applied to cure only this deficiency. The affidavit does not expressly recite that this claim element was contributed by the inventor of the claimed invention or not. On the contrary, Razavi, expressly recites that pFUS parameters selected were previously shown in studies to be safe in animals (Razavi last page). This additionally suggests these parameters could have been possibly been discovered by someone other than the co-authors of the reference Razavi. Hence the examiner maintains that the affidavit is insufficient to overcome the reference Razavi.
Claims 1-3, 13-22, 24-29, 41, 50-55 have additionally been rejected under new grounds of rejection 35 USC § 103.
Affidavit or Declaration Under 37 CFR 1.130
The declaration under 37 CFR 1.130 filed 06/13/2025 is insufficient to overcome the rejection of claims 1-3, 13-22, 24-29, 41, 50-55 based upon 35 USC § 103, as set forth in the last Office action because:
The affidavit or declaration does not show sufficient facts, in weight and character, to establish that the subject matter disclosed was obtained directly or indirectly from the inventor or a joint inventor. The declaration on page 2, section 3 does not establish that the subject matter of the invention was fully contributed by the inventor, what parts of the works in Razavi were contributed by the inventor, or what parts of the works in Razavi were contributed by others noted in the reference Razavi. Additionally, in this case, it is not clear whether or not the limitations regarding the powers (Specifically ISAPA of 272 W/cm2) were contributed by the inventor or others. There is no affidavit from others regarding this. Further, a statement that “contribution to the conception of the subject matter”, is vague, since the scope of this statement is broad, and hence not sufficient to make a determination that the subject matter disclosed (in this case, regarding the power) was obtained directly or indirectly from the inventor or a joint inventor.
Applicant’s arguments regarding 103 rejection in view of Burks (remarks pages 8-9), are considered persuasive and is withdrawn.
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.
Claims 1, 3, 13-22, 24-27, 29, 41, 50-55 rejected under 35 U.S.C. 103 as being unpatentable over Burks [Mesenchymal stromal cell potency to treat acute kidney injury increased by ultrasound‐activated interferon‐γ/interleukin‐10 axis, J Cell Mol Med. 2018 Sep 14;22(12):6015–6025] in view of Razavi [Improving the Function and Engraftment of Transplanted Pancreatic Islets Using Pulsed Focused Ultrasound Therapy, https://doi.org/10.1038/s41598-019-49933-0, 2019].
As per claim 1, Burks teaches a method of treating damaged kidney tissue in a subject (Burks Title), the method comprising locally administering to the damaged kidney tissue a therapeutically effective amount of pulsed focused ultrasound (pFUS) therapy Burks section 2.1 and 2.2, delivering pFUS to AKI induced mice) in combination with a therapeutically effective amount of mesenchymal stromal cells (MSCs) or MSC-derived extracellular vesicles (Examiner choses MSCs. Burks abstract “Mesenchymal stromal cell (MSC) therapies combined with renal pulsed focused ultrasound (pFUS)” section 2.3, infusing MSC post pFUS).
Burks does not expressly teach wherein the pFUS therapy is administered with a spatial average pulse average intensity (Isapa) of about 272 W/cm2.
Razavi, in a related field of pulsed focused ultrasound (pFUS) therapy, teaches wherein the pFUS therapy is administered with a spatial average pulse average intensity (Isapa) of about 272 W/cm2 (Razavi Page 10 “To treat the whole kidney, non-overlapping adjacent regions through the kidney were targeted for 30 sec per region. The time to treat one kidney with these parameters was approximately 4 min. In order to deliver pFUS therapy to the animal, the HIFU transducer was used with the following parameters: 5% DC, 5 Hz PRF, 2.9 MPa PNP, and 272 W/cm2 Isapa, which has been shown in previous studies to be safe in small animals”).
As per MPEP 2413.I.G, “Examples of rationales that may support a conclusion of obviousness include… Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention”. Razavi discloses pFUS for treating kidneys, which is closely related to the claimed invention, and discusses the required Isapa so that it is safe in small animal studies. Before the effective filing date of the claimed invention it would have been obvious to a person of ordinary skill in the art to utilize HIFU transducer parameter for kidney treatments as in Razavi so that safe levels for of pFUS for treating kidneys can be implemented.
As per claim 3, Burks in view of Razavi further teaches wherein the pFUS therapy is administered with an ultrasound frequency of about 1.1 MHz (Razavi Table 2 on page 10 discloses this frequency). Applicant specification discloses multiple parameters and frequencies and their combinations mentioned (See spec. ¶0007-¶0011, ¶0124) and this claim recites ones out of them. The specification does not provide any reason why these particular parameters would be preferred over others mentioned. The specification does not set forth evidence that such values are critical, and of both statistical and practical significance. Hence, the teaching in Razavi would be an obvious parameters to use since, it was utilized in kidney treatments.
As per claims 13, 14, Burks in view of Razavi further teaches wherein the pFUS therapy is administered to the subject for at least 30 seconds, or wherein the pFUS therapy is administered to the subject for a period ranging from about 1 minute to about 5 minutes (Razavi “To treat the whole kidney, non-overlapping adjacent regions through the kidney were targeted for 30 sec per region. The time to treat one kidney with these parameters was approximately 4 min”). .
As per claim 15, Burks in view of Razavi further teaches wherein the pFUS therapy is administered at a single location or at multiple locations in the kidney (Burks section 2.2, 100 pulses of 10 ms length implies 1 second per location. Further there are 9-12 loci are disclosed).
As per claims 16-17, Burks in view of Razavi further teaches wherein imaging the damaged kidney tissue, wherein said imaging is performed by ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), or scintigraphy (Burks section 2.2 “pFUS was delivered under ultrasound imaging guidance”).
As per claim 18, Burks in view of Razavi further teaches wherein the MSCs are from bone marrow or adipose tissue (Burks section 2.3 “Human MSCs were donated to the NIH Center for Bone Marrow Stromal Cell Transplantation under the clinical trial NCT01071577 (www.clinicaltrials.gov),” Clinical trial NCT01071577 attached with PTO 892).
As per claim 19, Burks in view of Razavi further teaches wherein the kidney tissue is damaged from an acute kidney injury or chronic kidney disease (Burks relates to AKI, for e.g. see abstract).
As per claim 20, Burks in view of Razavi further teaches wherein the acute kidney injury is caused by chemotherapy, a chemical exposure, surgery, or a traumatic physical injury (Burks abstract “cisplatin‐induced acute kidney injury (AKI)”. Cisplatin is a chemotherapy drug).
As per claims 21-22, 24-25, Burks in view of Razavi further teaches wherein the MSC- derived extracellular vesicles are exosomes or microvesicles, wherein the MSC-derived exosomes comprise one or more surface markers selected from the group consisting of CD9, CD63, and TSG101, wherein the MSC- derived extracellular vesicles have diameters ranging from about 20 nm to 180 nm, wherein the MSC-derived extracellular vesicles have a mean diameter of 118 nm (These limitations as recited is does not limit the parent claim, since the “MSC- derived extracellular vesicles” are recited in the optional form in the parent claim. examiner did not choose this option in the parent claim).
As per claim 26, Burks in view of Razavi does not expressly teach wherein multiple cycles of treatment are administered to the subject. However, this is only directed to repeating the method of claim. There is no additional step claimed. Medical treatments and subject dependent and varies with different factors such as weight, height etc.… Medical professionals prescribe dosages /durations / repetitions according to these factors, and if necessary. It would be obvious to provide multiple cycles so that customized treatment can be provided if necessary.
As per claim 27, it has limitations similar to claim 1 and is rejected for same reasons as above. It is noted that the recitation of “ suppressing NLRP3 inflammasome-mediated inflammation in a subject” is intended use and does not result in a manipulative difference between the claimed invention and the prior art. See MPEP 2111.02.II.
As per claims 29, 41, they have limitations similar to claims 3, 15 and are rejected for same reasons as above.
As per claims 50-55, Burks in view of Razavi further teaches wherein the pFUS therapy is administered with a pulse repetition frequency (PRF) of about 100 Hz, or wherein the pFUS therapy is administered with an ultrasound duty cycle of about 20% (Razavi page 9, “For the in vitro experiments, the transducer was used with the following parameters: 1 MHz, 2000 cycle, sinusoidal pulses at a pulse repetition frequency (PRF) of 100 Hz for a 20% duty cycle (DC)”), and wherein the pFUS therapy is administered with a negative peak pressure (NPP) of about 3 MPa (See applicant spec. ¶0061 regarding term “about”. Razavi page 10 “In order to deliver pFUS therapy to the animal, the HIFU transducer was used with the following parameters: 5% DC, 5 Hz PRF, 2.9 MPa PNP”). Applicant specification discloses multiple parameters and frequencies and their combinations mentioned (See spec. ¶0007-¶0011, ¶0124) and this claim recites ones out of them. The specification does not provide any reason why these particular parameters would be preferred over others mentioned. The specification does not set forth evidence that such values are critical, and of both statistical and practical significance. Hence, the teaching in Razavi would be an obvious parameters to use since, it was utilized in kidney treatments.
Claims 2, 28 rejected under 35 U.S.C. 103 as being unpatentable over Burks in view of Razavi as applied to claims 1, 27 above and further in view of Westenfelder [US 20080241112 A1].
As per claims 2, 28, Burks wherein the MSCs or the MSC-derived extracellular vesicles are administered locally to the damaged kidney tissue intra-arterially via a renal artery.
Westenfelder teaches wherein the MSCs or the MSC-derived extracellular vesicles are administered locally to the damaged kidney tissue intra-arterially via a renal artery (Westenfelder ¶0056 “Preferably, MSC, EC, and MSC CM may be administered to the patient by injection or instillation intravenously (i.e., large central vein such vena cava) or intra-arterially (i.e., via femoral artery into supra-renal aorta).”).
Burks recites injecting MSCs through lateral tail vein. Before the effective filing date of the claimed invention it would have been obvious to a person of ordinary skill in the art to modify the method in Burks by using intravenous injection for MSCs as in Westenfelder. This modification is only directed to “Simple substitution of one known element for another to obtain predictable results” as in MPEP 2143.I.B. The predicable result is that MSC can be injected into subject for treating kidney disorders.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OOMMEN JACOB whose telephone number is (571)270-5166. The examiner can normally be reached 8:00-4:00.
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/Oommen Jacob/ Primary Examiner, Art Unit 3797
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