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 .
Acknowledgments and Claim Status
The Examiner acknowledges receipt of the amendment filed 4/10/2026 wherein claims 4-6, 8, 9, 11, 12, 14-25, 27, 29-34, 37-40, 42, 44-50, 52, 53, 55, 57, 58, 60-63, 65, and 67 were canceled.
Note(s): Claims 1-3, 7, 10, 13, 26, 28, 35, 36, 41, 43, 51, 54, 56, 59, 64, and 66 are pending.
Priority and Priority Document
This application claims priority to CANADA CA3168590 filed 7/23/2022.
Acknowledgment is made of Applicant’s claim for foreign priority under 35 USC 119 (a) – (d). The certified copy has been filed in with the pending application on 1/11/2024.
Note(s): The earliest effective filing date is 7/23/2022 because the pending invention is fully supported in CANADA CA3168590.
Claim Interpretation
Independent claim 1 is directed to a ratiometric detection composition comprising (1) a reference dye, the reference dye being a first cyanine dye that is PEGylated and (2) a sensor dye, the sensor dye being a second cyanine dye that is PEGylated and that comprises an analyte sensing moiety wherein the reference dye is inert towards the analyte; wherein an emission maximum wavelength of the reference dye and an emission maximum wavelength of the sensor dye are at least 50 nm apart; and wherein the first cyanine dye and the second cyanine dye are PEGylated with PEG groups of substantially the same molecular weight.
Claim 35 is directed to a microneedle array comprising (1) a backing layer and (2) a plurality of microneedles each having a first end and a second sharpened end for penetration into skin, the plurality of microneedles extending outwardly from the backing layer at the first end wherein the microneedles are formed with a biodegradable polymer and comprise a ratiometric detection composition as defined in claim 1 that is incorporated in the biodegradable polymer and wherein the plurality of microneedles is dissolvable and releasable from the backing layer after penetration into the skin.
Claim 41 is directed to a method of delivering a ratiometric detection composition to a subject comprising administering a microneedle array as defined in claim 35 to a skin of the subject.
Claim 43 is directed to a method of detection or measurement of an analyte comprising detecting in a subject that had been administered a ratiometric detection composition as defined in claim 1:
a fluorescence level of the reference dye;
a fluorescence level of the sensor dye; and
assessing a presence of the analyte wherein a positive value of the fluorescence level of the sensor dye normalized to the fluorescence level of the reference dye is indicative of the presence of the analyte or determining a quantity of the analyte wherein a value of the fluorescence level of the sensor dye normalized to the fluorescence level of the reference dye is indicative of the quantity of the analyte.
Claim 51 is directed to a method of detection or measurement of ROS comprising detecting in a subject that is administered a ratiometric detection composition as defined in claim 3 a fluorescence level of the reference dye and a fluorescence level of the sensor dye and assessing a presence of the ROS wherein a positive value of the fluorescence level of the sensor dye normalized to the fluorescence level of the reference dye is indicative of the presence of the ROS or determining a quantity of the ROS wherein a value of the fluorescence level of the sensor dye normalized to the fluorescence level of the reference dye is indicative of the quantity of the ROS.
Claim 54 is directed to a method of measurement of pH, the method comprising detecting in a subject that is administered a ratiometric detection composition as defined in claim 10 a fluorescence level of the reference dye and a fluorescence level of the sensor dye and determining a pH value wherein a value of the fluorescence level of the sensor dye normalized to the fluorescence level of the reference dye is indicative of the pH value.
Claim 56 is directed to a method of detection or measurement of a cation, the method comprising detecting in a subject that is administered a ratiometric detection composition as defined in claim 13 a fluorescence level of the reference dye and a fluorescence level of the sensor dye and assessing a presence of the cation wherein a positive value of the fluorescence level of the sensor dye normalized to the fluorescence level of the reference dye is indicative of the presence of the cation or determining a quantity of the cation wherein a value of the fluorescence level of the sensor dye normalized to the fluorescence level of the reference dye is indicative of the quantity of the cation.
Clarification of the Record
In the restriction requirement mailed on 2/11/2026, claim 64 was inadvertently placed in Group I instead of Group IV. Specifically, claim 64 depends from claim 35 which is in Group IV along with the other claims that depend upon claim 35. Furthermore, it is duly noted that the invention of Group IV is distinct from that of Group I as the two invention are not obvious modifications of one another. Thus, updated Group I is directed to pending claims 1-3, 7, 10, 13, 26, 28, and newly added claim 66. Updated Group IV contains pending claims 35, 36, and 64.
Applicant’s Election
Applicant's election with traverse of Group I (pending claims 1-3, 7, 10, 13, 26, 28, and 66) filed 4/10/2026 is acknowledged. The traversal is on the grounds that claims 35 and 36 are unified with Group I claims and/or that it would not be a serious burden on the Examiner to search the claims of both Groups I and IV. In addition, it is asserted that the kit claim (claim 64) was included in the restriction requirement mailed 2/11/2026. This is found non-persuasive because Groups I and IV are not obvious modifications of one another. Specifically, Group IV (e.g., claim 35) is directed to a device/instrument (microneedle array) and Group I is directed to a composition. Additional components are necessary outside of the compositional components of Group I. Furthermore, it is noted that once again noted that Group I and Group IV are not obvious variants of one another.
In regards to Applicant’s assertion that the kit claim (claim 64) was included in Group I the restriction requirement mailed 2/11/2026, the following response is given. Claim 64 depends from claim 35 which is in Group IV along with the other claims that depend upon claim 35. It is clear that claim 64 was inadvertently included into the wrong group. The invention of Group IV is distinct from that of Group I as the two invention are not obvious modifications of one another. Updated Group I is directed to pending claims 1-3, 7, 10, 13, 26, 28, and newly added claim 66. Updated Group IV contains pending claims 35, 36, and 64.
For the reasons supra, the restriction requirement is still deemed proper and is therefore made FINAL.
Applicant elected the species wherein the reference dye is
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wherein n is about 90 to about 30; the sensor dye is
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; the analyte is Na+; the backing layer (polymer of interest) is PVP; microneedle polymer of interest is PVP; and the application device is a spring loaded applicator device. Clams 1-3, 7, 10, 26, 28, and 66 read on the elected species. Initially, Applicant’s elected species was searched and no prior art was found to reject the claims. Thus, the search was expanded to the cited prior art below. Since prior art was found to reject the claims, the search was not further extended.
Withdrawn Claims
Claims 13, 35, 36, 41, 43, 51, 54, 56, 59, and 64 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention/species.
Information Disclosure Statement
The two information disclosure statements filed 3/26/2025 were considered.
Written Description Rejection
The following is a quotation of the first paragraph of 35 U.S.C. 112(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.
Claim 1 is 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.
Applicant is reminded that an inventor is entitled to a patent to protect his work only if he/she produces or has possession of something truly new and novel. The invention being claimed must be sufficiently concrete so that it can be described for the world to appreciate the specific nature of the work that sets it apart from what was before. The inventor must be able to describe the item to be patented with such clarity that the reader is assured that the inventor actually has possession and knowledge of the unique composition that makes it worthy of patent protection. The pending application does not sufficiently describe the invention as it relates to reference and sensor dyes other than:
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, and
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. Thus, what the reader gathers from the instant application is a desire/plan/first step for obtaining a desired result. While the reader can certainly appreciate the desire for achieving a certain end result, establishing goals does not necessarily mean that an invention has been adequately described.
While compliance with the written description requirements must be determined on a case-by-case basis, the real issue here is simply whether an adequate description is necessary to practice an invention described only in terms of its function and/or based on a disclosure wherein a description of the components necessary in order for the invention to function are lacking. In order to satisfy the written description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. In other words, the specification should describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that the inventor created what is the claimed. Thus, the written description requirement is lacking in the instant invention since the various terms as set forth above are not described in a manner to clearly allow persons of ordinary skill in the art to recognize that Applicant invented what is being claimed.
112 Second Paragraph Rejections
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 2, 3, 7, 10, and 66 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.
Claims 2, 3, 7, and 66: The claims are ambiguous because they do not define the meaning of the broken structure (structure with hashmarks) appearing in the claims.
Claim 7: The claim recites the limitation "the analyte sensing moiety" in line 10. There is insufficient antecedent basis for this limitation in the claim. In addition, the claim is ambiguous because of the phrase ‘the analyte sensing moiety’. Specifically, it is unclear what substances Applicant is referencing that are applicable as analyte sensing moieties.
Claim 10, lines 8, 15, and 20: Applicant is respectfully reminded that a proper Markush grouping requires a closed list of substances (see MPEP 803.02). Thus, the phrase ‘and/or’ is not consistent with MPEP 803.02. Did Applicant intend to write that the dye is one or more of those appearing in claim 10?
Claim 66: The claim is confusing because of the phrase ‘a combination comprising a reference dye and a sensor dye’. Specifically, this is what independent claim 1 requires (a reference dye and a sensor dye). Also, the ‘optionally, the dye...thereof’ is an optional component and does not require that particular reference dye to be present.
103 Rejection
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.
Claims 1, 2, 26, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Babity et al (Adv. Healthcare Mater., online Dec. 23, 2021, Vol. 11, No. 2102070, pages 1-15).
Independent claim 1 is directed to a ratiometric detection composition comprising (1) a reference dye, the reference dye being a first cyanine dye that is PEGylated and (2) a sensor dye, the sensor dye being a second cyanine dye that is PEGylated and that comprises an analyte sensing moiety wherein the reference dye is inert towards the analyte; wherein an emission maximum wavelength of the reference dye and an emission maximum wavelength of the sensor dye are at least 50 nm apart; and wherein the first cyanine dye and the second cyanine dye are PEGylated with PEG groups of substantially the same molecular weight.
Claim 2 is directed to the reference dye,
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wherein the 6-membered broken ring (structure in hashtag) is optionally present.
Claim 26 is directed to a composition comprising
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and/or
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.
Claim 28 is directed to the various structures therein.
Babity et al is directed to a ratiometric fluorescent compounds (see entire document, especially abstract). In particular, Babity et al disclose Cys5-PEG and H-Cys5-PEG wherein the fluorescence is at wavelength 646 nm; 666 nm (page 3, Figure 1; page 3, left and right column, bridging paragraph). On page 5, Figure 2, the sensitivity of H-Cy5-PEG in the presence of Cy3-PEG is evaluated. A reference dye was incorporated into the composition to act as an internal standard (Cy3-PEG is the reference dye). Cy5 fluoresces at 788 nm; 808 nm (pages 7-8, bridging paragraph; page 9, Figure 5). Both Cys5-PEG and Cy3-PEG were optimized for delivery to the skin (pages 5-6, bridging paragraph; page 6, left column, first complete paragraph; page 6, left column, third complete paragraph).
Compositions comprising both H-Cy5-PEG and Cy3-PEG were prepared (page 6, right column, first complete paragraph; page 7, Figure 3). The inclusion of a reference dye (e.g., Cy3-PEG) allows the composition to function as a ratiometric sensor (page 6, right column, second complete paragraph). The fluorescence of Cy5-PEG and Cy7.5-PEG were evaluated as Cy7.5 is the inert reference (page 8, left column, first appearing paragraph; page 8, right column, first paragraph; page 9, Figure 6; page 12, ‘Preparation of ...H-Cy5-PEG and Cy3-PEG or Cy7.5-PEG’; page 12, right column, fourth complete paragraph; pages 12-13, bridging paragraph). For Cy5, the excitation wavelength was set forth 640 nm and the emission wavelength is 720 nm while the emission wavelength is 720 nm (page 13, left column, second complete paragraph). Thus, both Applicant and Babity et al disclose compositions having both a reference and sensor component wherein the dye components having the structures,
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and
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(page 3, Figure 1).
For the reasons set forth supra, a composition comprising a reference dye and a sensor dye as set forth in independent claim 1 is present in both the cited prior art and the pending invention. Thus, the inventions disclose overlapping subject matter. Hence, the limitations of claims 1, 2, 26, and 28 are met.
Comments/Notes
Applicant is respectfully reminded that the full scope of pending Group I was not searched.
Conclusion
Claims 1-3, 7, 10, 26, 28, and 66 are rejected. Claims 13, 35, 36, 41, 43, 51, 54, 56, 59, and 64 are withdrawn.
Future Correspondences
Any inquiry concerning this communication or earlier communications from the examiner should be directed to D L Jones whose telephone number is (571)272-0617. The examiner can normally be reached M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael G. Hartley can be reached at (571)272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
June 17, 2026
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