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 .
DETAILED ACTION
This Office Action is a response to Applicant’s Arguments/Remarks filed November 25, 2025.
Claims 21-40 are pending in the present application.
Claims 35-40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 14, 2025.
Claims 21-34 have been examined on the merits as detailed below:
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 112
In the previous Office Action mailed July 3, 2025, claims 21-34 were rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. This rejection is withdrawn in view of Applicant’s Arguments/Remarks filed November 25, 2025.
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In the previous Office Action mailed July 3, 2025, claims 21-34 were rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of stimulating sodium appetite in a subject in need thereof, the method comprising: stimulating a plurality of prodynorphin (PDYN)-positive neurons in the pre-locus coeruleus (pre-LCPDYN neurons) of the subject, wherein stimulating the plurality of pre-LCPDYN neurons of the subject comprises the optogenetic activation of pre-LCPDYN neurons by adeno-associated virus (AAV) encoding Cre-dependent channelrhodopsin (AAV-DO-ChR2) infected into the pre-LC of PDYN-Cre the subject, thereby increasing sodium ingestion of the subject, following the optogenetic stimulation of neurons in the pre-LC that express PDYN, does not reasonably provide enablement for a method of stimulating sodium appetite in a subject in need thereof, the method comprising: stimulating a plurality of prodynorphin (PDYN)-positive neurons in the pre- locus coeruleus (pre-LCPDYN neurons) of the subject, thereby increasing sodium appetite in the subject. This rejection is withdrawn in view of Applicant’s Arguments/Remarks filed November 25, 2025.
After careful reconsideration of the claims, a new grounds of rejection is made of record as detailed below:
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 21-34 are rejected under 35 U.S.C. 103 as being unpatentable over Jarvie et al. (Nature Neuroscience, 2017 Vol. 20(2):167-169) (submitted and made of record on the Information Disclosure Statement filed February 16, 2024) as evidenced by Lee et al. (Nature, April 4, 2019, Vol. 568:93-97, plus Extended Data) and Sangjun Lee, Doctor of Philosophy Thesis, CALIFORNIA INSTITUTE OF TECHNOLOGY, (Defended May 15th, 2020) (both references submitted and made of record in the previous Office Action filed July 3, 2025).
The claims are drawn to a method of stimulating sodium appetite in a subject in need thereof, the method comprising: stimulating a plurality of prodynorphin (PDYN)-positive neurons in the pre-locus coeruleus (pre-LCPDYN neurons) of the subject, thereby increasing sodium appetite in the subject.
The present Specification is explicit in disclosing:
“Stimulating the plurality of pre-LCPDYN neurons of the subject can comprise, for example, optogenetic or chemogenetic stimulation”;
“For optogenetic activation of pre-LCPDYN neurons, adeno-associated virus (AAV) encoding Cre-dependent channelrhodopsin (AAV-DIO-ChR2) was infected into the pre-LC of PDYN-Cre animals”; and
“For chemogenetic manipulation (FIGS. 8E-H), CNO (Sigma, 10 mg/kg) or vehicle (water) was administered intraperitoneal 20 min before the sodium consumption experiment”.
Jarvie is relevant and relied upon in its entirety. Regarding claims 21, 26 and 33, Jarvie taught that chemogenetic stimulation of nucleus of the solitary tract (NTS) HSD2 (NTSHSD2) neurons with CNO was found to be sufficient to drive, or stimulate, the consumption of sodium-containing solutions in male and female mice.
Jarvie do not necessarily teach stimulation of pre-LCPDYN neurons.
Both Lee et al. and the Lee Thesis evidence that the stimulation of HSD2 neurons will subsequently activate downstream pre-LCPDYN neurons. More specifically, pre-LCPDYN neurons receive monosynaptic excitatory inputs from NTSHSD2 neurons. Therefore, chemogenetic stimulation of the upstream NTSHSD2 neurons leads to the stimulation and activation of the downstream pre-LCPDYN neurons.
Jarvie taught that administration of AAV1-DIO-hM3Dq:mCherry or CNO specifically targeted and activated NTSHSD2 neurons in the hindbrain. The evidence of both Lee et al. and the Lee Thesis demonstrate that stimulation of NTSHSD2 neurons activate pre-LCPDYN neurons. Given these teachings and disclosures, the method steps of Jarvie will inherently carry out the methods as present claimed, absent some evidence to the contrary. See MPEP 2112 with respect to inherency.
Further, the instant Specification serves as evidence of record establishing this inherency. Failure of those skilled in the art to contemporaneously recognize an inherent property (i.e. a biological mechanism of action) of a prior art reference does not preclude a finding of anticipation. Atlas Powder Co. v. IRECO, Inc., 190 F.3d 1342, 1349, 51 USPQ2d 1943, 1948 (Fed. Cir. 1999). See also Ex parte Novitski, 26 USPQ2d 1389 (Bd. Pat. App. & Inter. 1993).
Note that the Patent Office does not have the facilities and resources to provide the factual evidence needed in order to determine properties between the instantly claimed method of stimulating sodium appetite in a subject in need thereof, the method comprising: stimulating a plurality of pre-LCPDYN neurons of the subject, thereby increasing sodium appetite in the subject and the method of stimulating sodium appetite in a subject in need thereof, the method comprising: stimulating NTSHSD2 neurons of the subject, thereby increasing sodium appetite in the subject taught by the prior art. In the absence of evidence to the contrary, the burden is upon the Applicant to prove that the claimed method and associated method steps are different from the method and associated methods steps taught by the prior art, thereby establishing patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ2d 1922(PTO Bd.Pat. App. & Int. 1989).
The Examiner has provided sound basis in fact and technical reasoning that reasonably supports the determination that the allegedly inherent characteristic necessarily flows from what has been specifically disclosed within the prior art and has shifted the burden to Applicant to provide evidence, to the contrary. Again, the method steps of Jarvie will inherently carry out the methods as present claimed.
Regarding claims 22 and 23, Jarvie taught determining sodium intake before and after chemogenetic stimulation.
Regarding claims 24 and 25, Jarvie taught NTSHSD2 neurons project to specific downstream sites, including the ventral bed nucleus of the stria terminalis (vBNST). Both Lee et al. and the Lee Thesis evidence that chemogenetic stimulation of HSD2 neurons in turn propagates a signal to activate pre-LCPDYN neurons and further comprises inhibiting a plurality of GABAergic neurons in the bed nucleus of the stria terminalis (BNST); and inhibiting GABAergic neurons in the central amygdala.
Regarding claim 27, Jarvie teach sodium appetite is increased by at least 50%.
Regarding claim 28, Jarvie teach sodium appetite is increased within 15 minutes from the onset of stimulation.
Regarding claims 29-32 which recite frequency or concentration of sodium ingestion, Both Lee et al. and the Lee Thesis evidence that chemogenetic stimulation of HSD2 neurons propagates a signal to activate pre-LCPDYN neurons leading to changes in frequency or concentration of sodium ingestion in a subject as recited in the claims.
Before the effective filing date of the claimed invention, deciphering the neuronal circuits that drive salt seeking behavior by studying the effect of manipulation of neuron activity in salt appetite was highly studied in the prior art. The prior art of Jarvie taught the excitation of NTS HSD2 neurons drives sodium appetite. Jarvie also taught that HSD2 axonal neurons project to the pre-LC.
At the time of invention, a method of stimulating sodium appetite in a subject in need thereof, the method comprising: stimulating NTSHSD2 neurons of the subject, thereby increasing sodium appetite in the subject was known as taught and suggested by Jarvie. Evidence on the record demonstrates that signals/connections from NTSHSD2 neurons are transmitted to a subset of excitatory neurons characterized by the expression of prodynorphin (PDYN) in the pre-locus coeruleus (pre-LC). See Lee et al. and the Lee Thesis. That is, activation of the upstream HSD2 neurons leads to the stimulation and activation of the downstream pre-LC PDYN neurons.
A person of ordinary skill in the art would have been motivated to include a subject suffering from hyponatremia or excessive sweating in the teachings of Jarvie to more efficiently balance the amount of fluid (water) in the subject.
A person of skill in the art would have expected reasonable success to devise the method of the claimed invention using the teachings, suggestion and motivation of Jarvie.
Absent a Declaration providing a direct comparison of the claimed invention with the closest prior art of Jarvie and an explanation of why the results of the present invention would have been unexpected by one of ordinary skill in the art, the Examiner maintains that the instant claims would have been prima facie obvious over the prior art. Therefore, claims 21-34 are rejected under 35 U.S.C. 103 as being unpatentable over Jarvie as evidenced by Lee et al. and the Lee Thesis, absent evidence to the contrary.
Conclusion
No claims are allowable at this time.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635