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 .
Claim Rejections - 35 USC § 112
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, 1-2 and 9-10 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In this instance and regarding Claim 1, the claim iterates “A photoacoustic ion indicator for detecting ion concentration within a neuron” while also iterating that the structure at issue (see figure/depiction in claim 1) which consists of that structure with no other structures present (i.e. it does not consist of, contain, or comprise one or more acetoxymethyl esters [hereafter AM]). However, all embodiments contained within the specification, e.g. see applicant’s specification at [0008] or [0101], appear to use AM in order to access/penetrate the neuron. Likewise, while a lack of limitation cannot have a specific citation the examiner notes that he applicant explicitly provide the opposite case which can be cited directly. For instance the applicant does explain why they use AM and why it is advantageous as per [0002] the field is neuronal ion concentration detection, [0003]-[0007] explain the need to and set out to develop new means for neuronal ion concentration detection, [0008] explains that the ion indicator developed to solve these issues uses AM to allow the ion indicator to enter the neurons and e.g. states “wherein the photoacoustic ion indicator is impermeable through the membrane of the neuron when the one or more acetoxymethyl esters are cleaved from the one or more polar groups” seemingly explicitly calling the claimed form of the invention unsuitable for the purpose set forth in the preamble of the claim. Therefore, the claim contains new matter not adequately supported by the orientally filed disclosure.
For compact prosecution purposes the examiner recommends either removing that the invention is for use “within a neuron” from the preamble, or adding AM back into the body of the claim, or changing claim 1 to comprise but not consist of the currently claimed ion indicator structure; any of which would resolve the issue.
Claims 2 and 9-10 are similarly affected, at least by virtue of dependency.
Claim Rejections - 35 USC § 103
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.
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.
Claim(s) 1-2, 5-7, and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Fluorescent Indicators for Cytosolic Sodium by Minta et al. (hereafter Minta, previously of record).
Regarding claim 1, Minta teaches: 1. A photoacoustic ion indicator for detecting ion concentration within a neuron (see Minta’s title and Abstract which show that this is an ion indicator for detecting concentration of ions within body cells in general. Further noting that while Minta’s invention is directed towards fluorescent sensing that this preamble limitation specifying the intended use of the indictor which, in accordance with MPEP 2111, does not confer structures such as US detector or the like), the wherein the photoacoustic ion indicator is selected from the group consisting of:
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wherein the photoacoustic ion indicator selectively binds to an ion selected from the group consisting of sodium, calcium, and potassium (see Minta’s Figure labeled “Fluorescent Indicators for NA+” on page 19451 which includes, in salient part, the following depiction:
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which is notably identical to the ion binding motif (i.e. 1 aza 15 crown 5 ether) and manner of attachment used in the applicant’s first two claimed options and the only ion binding motif pertinent to the elected species and where the very title of the figure and/or rote same structure, renders clear that this is capable of chelating/configured to chelate sodium ions though this is also established textually in Minta’s Discussion section on pages 19454-19456 and/or Table 1).
For compact prosecution purposes the examiner also notes that Minta’s invention further includes one or more acetoxymethyl esters, but appears to do so without necessarily running afoul of the applicant’s new “consisting of” claim limitation per se (i.e. while the product/injectable form of Minta’s ion indicator would not “consist of” only the contents iterated above, the intracellular/in use form would. Specifically, see the left column of Minta’s page 19450 noting that the acetoxymethyl esters are designed to be hydrolyzed (i.e. cleaved), and see Minta’s page 19450 noting that acetoxymethyl esters are used as a protecting group to allow for membrane permeation without microinjection, and also covering the that the fact that this is a polar group which is removed by hydrolysis (i.e. via an esterase – thought that is not a structure of the invention) allowing for cellular retention of the final product, where the final product is, at least as modified below, identical to and consists only of the claimed structure and thus would still be in accordance with the claim after cleavage within the neuron)
Minta additionally teaches using a chromophore, labeled “Ar” in the excerpt from Fig 1 above, (see Minta’s Table 1 noting the absorbance maxima and noting that this column is broken down in to -Na+ and +Na+ showing the absorbance change for each of the utilized indictors. For compact prosecution purposes the examiner also notes the key of table 1 (i.e. specifically that the stated numbers are 1/ 10^3, necessary for understanding the rejection of dependent claims/specified limitations) and also the examiner notes that the chromophore is again textually described in the Discussion section on pages 19454-19456 wherein Minta uses various aryl or styryl chromophores)
In the foregoing the examiner notes that Minta does not specify the necessity of using any particular chromophore and instead generally requires only that the chromophore have a sufficiently long absorption and/or emission wavelengths (see e.g. Minta’s page 19450 last paragraph in the left column) and Minta even clarifies that they only settled on using aryl and styryl chromophores because they were commercially available already bonded to the 15-crown-5 ether that was essential for Na+ chelation (see Minta’s Discussion section noting the paragraph bridging pages 19454-19455 and noting in particular that the 15-crown-5 ether was “commercially available, it could be attached as a preformed unit to a variety of aryl chromophores, enabling a considerable number of the latter to be tested without too much effort”). Therefore, while Minta’s invention is otherwise identical in structure to the applicant’s invention, Minta fails to teach linear acene chromophores per se and thus fails to teach that the chromophore “Ar” should be tetracene or pentacene as iterated in the newly claimed figures.
To that end the examiner notes that the applicant should take official notice that numerous linear acenes (including tetracene and pentacene per se, with references previously/already of record for these two now claimed linear acenes in specific, and with tetracene already specifically addressed below, and with new art in the conclusion section that addresses the suitability of tetracene and pentacene for use as chromophores when bonded to aza crown ethers of the sort used by Minta and by the applicant) are old and well known in the art as are the optical properties thereof including possessing optical absorption and emission wavelengths which are suitable long and including the ability to be used in fluorescent applications; wherein the absorption and/or emission wavelengths of many of these linear acenes, e.g. with anthracene being a common fluorescent dye with emission peaks longer than any of Minta’s dyes and tetracene being a dye commonly used as a gain medium in dye lasers, are actually longer than the aryl and styryl chromophores employed by Minta which were found acceptable as per Minta’s Table 1. See MPEP 2144.03 and MPEP 2144.07.
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the date of invention to improve the indicator of Minta with the use of linear acene chromophores because they are well understood to have suitable optical properties for Minta’s needs.
Regarding claim 2, Minta further teaches: 2. The photoacoustic ion indicator of claim 1, wherein the ion is a sodium ion (as iterated above in claim 1, see Minta’s Fig. 1 and note that not only does Minta teach many different variants of chelating agents but that this specifically covers 15-crown-5 ethers per se, and many derivatives thereof. While it is self-evident that these preferentially bind Na+ see also Table 1 which establishes that this is for Na+ chelation per se and/or see the Discussion section on pages 19454-19456 which textually describes the various chelating agents used by Minta).
Regarding claim 9, Minta further teaches: 9. The photoacoustic ion indicator of claim 1,wherein the photoacoustic ion indicator exhibits a shift of at least one light absorption characteristic upon binding to the ion wherein the at least one light absorption characteristic comprises one or more of an absorption wavelength range, a peak absorption wavelength, a total absorption value, and an absorption coefficient (the examiner notes that it is inherent that these each change due to Na+ binding, but for compact prosecution purposes see Minta’s Table 1 which shows this clearly, e.g. the absorbance maxima (aka peak absorption wavelength)).
Regarding claim 10, Minta further teaches: 10. The photoacoustic ion indicator of claim 9, wherein the photoacoustic ion indicator has a peak absorption wavelength greater than about 350 nm after the shift (see Minta’s Table 1 noting that multiple indicators have a peak absorption over 350 nm after Na+ binding).
Response to Arguments
Applicant’s arguments, see page 8, filed 05/23/2025, with respect to 112(b) have been fully considered and are persuasive. The associated rejection of the previous office action has been withdrawn.
Applicant's arguments filed 05/23/2025 with respect to the prior art rejection have been fully considered but they are not persuasive as follows:
As an initial note, the rejection is moot with respect to the cancelled claims.
Regarding the remaining claims, the applicant argues on pages 8-9 that the KSR principles must be applied and thus the search a comparison of all limitations of the invention. While the examiner notes the emphasis, the examiner also notes that the argument does not point out any limitation not included. Thus, this argument must be treated as mere allegation and therefore this is not convincing.
The applicant then opines that in order to advance prosecution that they have amended the claim. The claim amendment is extensive and does cause the examiner to fundamentally redraft their rejection; however, the same art is applied in substantially the same way to reject this new claim formatting such that the argument is not convincing for the reasons iterated above in the examiner’s amended claim rejection which is incorporated herein to rebut the applicant’s allegation that the amendment renders the claims patentable.
Lastly the applicant concludes by requesting patentability by dependency and withdrawal of the species restriction. While the examiner notes that when claim 1 becomes patentable the argument would be convincing, the examiner believes this assertion to be premature given the foregoing rebuttal of the argument for patentability of claim 1.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure is as follows:
SYNTHESIS AND SPECTROSCOPIC CHARACTERISATION OF Y-SHAPED FLUOROPHORES WITH AN IMIDAZOLE CORE CONTAINING N-ARYL-AZA-CROWN ETHER by Dilek Bayramin is an NPL reference that is pertinent because it discusses the optical properties of various chromophores including tetracene or pentacene when these are bound to aza crown ether moieties. In this specific instance the indicator is bound to other indicators via branches off of an imidazole core, so as to likely not be ideal for in neuron imaging / entering neurons via AM chemistry, but since this limitation has been removed from the body of claim 1 a modification as simple as merely providing a portion of Bayramin’s fluorophore/omission may cause it to read on the claim. This is still not an ideal reference versus the applicant’s specification, but as the claims diverge therefrom the myriad references like Bayramin become more and more pertinent. Additionally, this also further supports the examiner’s previously taken and already supported position that linear acenes and in particular tetracene and pentacene per se are viable and well-known chromophores as Bayramin also discusses them as viable, see e.g. pages 5-6, when bonding them in a similar context and also provides further citations to the fact that optical properties of these chromophores are known.
Light-activated Rare Earth Cation interphase transport by Tianrui Li is another NPL reference which the examiner notes to be pertinent to the new scope of claim 1. Specifically, while the examiner notes that a species teaches a genus and has utilized the species of crown ether suitable for the elected species of Na binding, that other references such as Li teach how and why to choose crown ethers for ion binding. See e.g. Li’s Fig. 3 11, Tables 2-3 on pages 13-14, and text of page which explains how the size and chemistry of certain crown ethers are suitable for chelating various ions. As with the foregoing reference there is no indication that Li’s teachings are intended to be combined with neuron imaging / AM chemistry but, as this limitation has been removed from the body of the claim, Li now appears relevant.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 Michael S Kellogg whose telephone number is (571)270-7278. The examiner can normally be reached M-F 9am-1pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Pascal Bui Pho can be reached at (571)272-2714. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL S KELLOGG/Examiner, Art Unit 3798
/PASCAL M BUI PHO/Supervisory Patent Examiner, Art Unit 3798