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 § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 20 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because a “use claim” does not fall within one of the four categories of patent eligible subject matter.
"Use" claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961)("one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. § 101 "). In Ex parte Dunki, 153 USPQ 678 (Bd. App. 1967), the Board held the following claim to be an improper definition of a process: "The use of a high carbon austenitic iron alloy having a proportion of free carbon as a vehicle brake part subject to stress by sliding friction." In Clinical Products Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966), the district court held the following claim was definite, but that it was not a proper process claim under 35 U.S.C. 101: "The use of a sustained release therapeutic agent in the body of ephedrine absorbed upon polystyrene sulfonic acid." See MPEP 2173.05 (q).
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 1-20 are 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 photoactivation of more than one molecule of the fluorescent dye, which are spaced apart from each other by a minimum distance d, from the protected, non-fluorescent form into the activated form by way of at least two light-induced reactions comprising at least a first photolytic cleavage reaction of a photolabile group bound to a functional group of the fluorescent dye and at least a second photolytic cleavage reaction of a photolabile group bound to another functional group of the fluorescent dye, but does not reasonably provide enablement for the general “photoactivation…” as claimed and “…such that the photoactivation comprises at least two respective light-induced reaction steps” as in independent claims 1, 18, and 20. This is likewise seen with respect to independent claim 19 with the further constitution that the specification, while being enabled for a structure as in molecules of a fluorescent dye being localized in a sample, but does not reasonably provide enablement for the recited methodology in constitution with the generalized structure being labeled with the fluorescent dye.
Further, it is noted in all of independent claims 1, 18, 19, and 20 that while the preamble speaks to the localization of single molecules of a fluorescent dye in a sample, the body of the claims is absent this positive provision to the method wherein the fluorescent dye is provided within a sample and its molecules tracked therein.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The pertinent Wands Factors are described below and related with the above discussion, which further show that the claims lack a proper scope of enablement.
1) Level of ordinary skill in the art – a PhD level in fields as in biochemistry/molecular biology, optical microscopy, and biophysics.
2) Nature of the invention – development of methodology for localizing single molecules of a fluorescent dye in a sample, wherein the fluorescent dye is selectively convertible/photoswitchable from a protected, non-fluorescent state, into an active fluorescent state.
3) State of the prior art – Applicant provides discussion to admitted prior art in pars.[0003-0012] of Applicant’s pre-grant publication US 2023/0120931, such as in STED microscopy, RESOLFT microscopy, MINFLUX nanoscopy, localization microscopy for localizing single fluorescent dye molecules, in which these variants provide high-resolution fluorescence microscopy in which stimulation light (quenching/inhibiting fluorescence) is used in addition to excitation light (activation of the dye) to achieve high spatial resolution in the image.
4) Breadth of the claims – Extremely broad as the general provision to the photoactivation comprising “at least two light-induced reaction steps” provides a very wide range of photochemical reactions that range from natural systems to various technological applications and each of which have their own unique and particular mechanisms, and requirements therewith.
Photochemical reaction steps (herein “at least two light-induced reaction steps”) could include reactions such as: photosynthesis, photolysis, photoisomerization, photoinduced electron transfer, photocycloaddition, photorearrangement, photography, production of Vitamin-D, photodissociation, photosubstitution, photocatalysis, photooxidation, and photo-redox reactions.
Further, as in independent claim 19, in addition to the above, the constitution of a generic “structure” being labeled with the fluorescent dye, this recitation is completely vast in its breadth as a “structure” is given by any physical object or system thereof, being organic or inorganic, being of microscale, microscale, nanoscale, etc…and having a vast range of compositions that constrain its ability to be labeled and generate a high-resolution image as claimed, as well as being constrained in technical ability to adapt such labeling and imaging as claimed with the vast range of sizes, compositions, chemistry, etc…afforded by the vast physical objects or systems thereof that comprise such a “structure.”
5) The level of predictability/amount of experimentation required – highly unpredictable given the breadth of the claims in combination with a lack of sufficient disclosure to bridge the gap between the discussion that is provided to photolytic cleavage of various photolabile groups bound to different functional groups of the molecules of the fluorescent dye to that of the wide range of photochemical reactions (i.e. light-induced reactions) that are known to exist. This is likewise seen with respect to the disclosure’s lack of discussion as to “structure” and correlating such with the recited high-resolution imaging thereof with a fluorescent dye as claimed.
An undue amount of experimentation would be required in both cases given the far-reaching scope of the elements (at least two light-induced reaction steps, and structure), wherein the disclosure is absent further discussion to provide one of ordinary skill in the art with the engineering, biochemistry, and microscopy imaging thereof such a vast range of light-induced reaction schemes and vast range of “structures” to be labeled with the fluorescent dye in such applications.
An unreasonable amount of experimentation would be required given the large nexus between that which has been disclosed by Applicant and that which is known in the prior art.
6) Working Examples –
The specification is devoid of working examples let alone working examples that provide basis for the above-discussed vast breadth afforded to the claims.
In its most relevant portion, as in par.[0103], Applicant provides discussion to utilizing caged Q-rhodamine with a so-called carbopyronine backbone and two photolabile protecting groups that are provided at two different positions in the molecule and are selectively cleaved off to provide the activated form in both instances by UV light. This is similarly discussed as in pars.[0024-0025] that likewise discuss the sequential/tandem photolytic cleavage of a plurality of photolabile groups bound to functional groups at different position of the molecule.
The remaining disclosure (e.g. pars.[0026-0042,0104-0113]) discuss the general scanning, positional tracking, and image generation, but are without particulars to the photoactivation step beyond the discussion of sequential/tandem photolytic cleavage of a plurality of photolabile groups that are provided at two different positions in the molecule and are selectively photolytically-cleaved to provide the active state.
Examiner notes that par.[0110; and subsequent ones thereto the cited various embodiments] and fig. 6 purport six different embodiments A to F of the methods of the present disclosure, however, such tabulated form is both unclear and inadequate in providing to bridge the gap between the particular photoactivation discussed above and that afforded by the wide range of “light-induced reactions.”
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 1-20 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.
The metes and bounds of the methods of claims 1, 18, and 19, and concordantly the “use” as in claim 20 as it includes the method of claim 1, are indefinitely defined herein.
First, the “photoactivation” step is indefinitely defined as in claims 1, 18 (and 20), as the claim recites “…one or more molecules…” wherein a choosing of “one” renders the recited distance d without meaning, and likewise with respect to the subsequent steps that ultimately localize active dye molecules (i.e. plural). By this, it appears that Applicant intends to positively necessitate “more” by way of a recitation to a plurality of molecules of the fluorescent dye.
As it pertains to independent clam 19, the “photoactivation of a subset of the fluorescent dye” is indefinitely understood. The claim previously provides general labeling of the structure with the fluorescent dye, which does not provide to define or correlate what is meant by “a subset of the fluorescent dye” both in terms of correlation to the labeling provided thereto and in terms of a quantified number of parts/molecules/positions that are photoactivated by the recited step.
In connection with the “photoactivation” step in all of the cited claims, the recitation “…wherein the fluorescent dye is selected such that the photoactivation comprises at least two respective light-induced steps indefinitely provides for the sought fluorescent dye as well as the sought processes to the method.
The recitation itself conflates the idea of selecting a dye (i.e. a choosing of particular dye or range of dyes from that of a larger genus of dyes) with process steps to “at least two respective-light induced reaction steps.
By this, it appears that Applicant intends to further limit the initial “photoactivation” step by providing that such photoactivation comprises performing at least two respective light-induced reaction steps.
Further, it is noted in all of independent claims 1, 18, 19, and 20 that while the preamble speaks to the localization of single molecules of a fluorescent dye in a sample, the body of the claims is absent this positive provision to the method wherein the fluorescent dye is provided within a sample and its molecules tracked therein.
This calls into question the localization, wherein it appears that Applicant intends provide a positive step to the providing of the fluorescent dye in a sample.
Furthermore thereto, the metes and bounds of the recitation “at least two respective light-induced reaction steps” are indefinitely defined herein.
Applicant’s specification does not make clear the corresponding “light-induced reaction steps” that provide to convert from the protected, non-fluorescent form into the activated form as claimed.
Examiner notes that general discussion with respect to the broad and vague recitation of “at least two light-induced reaction” steps is found in pars.[0019,0024], but do not provide a definitive discussion as to what constitutes “at least two light-induced reaction steps” as claimed.
The specification goes on to discuss “the design of the photoactivation process in two or more reaction steps can be realized by different reaction schemes” in the latter states of par.[0024], however, such disclosure is not clear in terms of the reaction schemes nor clear in the correlation or definition as it pertains to the broadly-claimed “at least two light-induced reaction steps.”
Examiner notes discussion of binding a plurality of photolabile protecting groups to functional groups of the fluorescent dye and wherein parallel or sequential photolytic cleavage is utilized to simultaneously (parallel) or sequentially convert from the protected, non-fluorescent form into the activated form (see within par.[0024] starting at the second paragraph thereof and forward to the end of par.[0024]). There is further disclosure with respect to the number of light sources required and coincident incident same or different wavelengths required.
It appears Applicant intends to provide the alternative choosing of those items provided in dependent claim 14 and 15, and wherein discussion of this methodology with respect to photolytic cleavage of a plurality of bound photolabiles at functional groups of the fluorescent dye in a sequential or simultaneous fashion appears to potentially construe at least two light-induced reaction steps given by individual photocleavage of a plurality of photolabiles to respective functional groups, but this does not provide clarity or basis for the far wider recitation of “at least two light-induced reactions,” and is merely drawn to the best-inferred intention of Applicant that may be seen within the confines of the specification.
Furthermore to the above, it is not clear if an intervening step of quenching/inhibition is a part of the “at least two light-induced reactions” coincident with the recited “photoactivation” step.
[Examiner further notes that the independent claims themselves does not provide the fluorescent dye bound at a plurality of functional groups with a plurality of photolabile groups].
With regard to claims 7 and 8, the recitation of “used to form a plurality of illumination points…” is indefinitely defined in the active steps of the methodology that render the sought outcome in which a vague recitation of “used” presents indefinitely defined metes and bounds thereto.
With regards to claims 9-17, the recited steps are indefinitely provided for in the claim wherein, as discussed above, these “at least two light-induced reaction steps” are recited within a selection of a dye step, and not as in particular, active steps to further define the step of “photoactivating…” as in the independent claims.
Further, as in claim 18, the recitation “…wherein the value of d is such that the initial position estimates can be unambiguously associated with the activated fluorescence dye molecules…” is indefinitely recited in its metes and bounds in setting forth the value d.
The recitation “can be unambiguously…” is implicitly undefined in its metes and bounds as Applicant has set forth what can be, and does not provide what it is. A recitation of “can be unambiguously” does not provide clear metes and bound as it is indefinitely defined.
For example, does Applicant intend to recite “…wherein the value of d is such that the initial position estimates are associated with the activated fluorescent dye molecules…”? (herein, removing the phrase “can be unambiguously”).
Claim 20 is 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 20 is drawn to a “use claim” wherein its metes and bounds as to the active process(es) sought to obtain a particular application are indefinitely defined.
Applicant’s intentions are further not understood as the use claim incorporates the steps of claim 1, which speaks to a redundancy of the method of claim 1, and particular application/usage with particular, actively recited steps for achieving such application are indefinitely provided herein.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Chen et al. (US 2024/0142379) discloses methods and systems for imaging reaction products that includes each monomer comprising a fluorophore group exhibiting different fluorescence emission wavelength and which are uncaged substantially simultaneously, and images are obtained after the uncaging, which is considered relevant to Applicant’s field of endeavor.
Weber et al. (US 2022/0064452) discloses photoactivatable fluorescent dyes with hydrophilic caging groups wherein particular activation of spatiotemporal subpopulations of caged dyes allow imaging of the uncaged fluorophores while protecting the remaining caged fluorophores from photobleaching that is relevant to Applicant’s field of endeavor.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NEIL N TURK whose telephone number is (571)272-8914. The examiner can normally be reached M-F 930-630.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jill Warden can be reached at 571 272-1267. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NEIL N TURK/Primary Examiner, Art Unit 1798