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 .
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-2 and 4-8) in the reply filed on 6/5/26 is acknowledged. The traversal is on the ground(s) that all claims can be conducted without undue burden on Examiner. This is not found persuasive because the search of prior art for the different claimed limitations and consideration of issues such as 35 USC 112, 35 USC 102, 35 USC 103, etc. adds the burden of time and effort that is considered an undue burden on Examiner.
The requirement is still deemed proper and is therefore made FINAL.
Claims 3 and 9-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 6/5/26.
Claim Objections
Claims 1 and 2 are objected to because of the following informalities: the multiple capitalization of letters should be corrected such that there is only one capitalization at the beginning of the sentence. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 4 and 6 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.
Regarding claim 4, the phrase "such as", in lines 2 and 3, renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 6, the phrase "such as", in line 2, renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 4-6 and 8 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Yelleswarapu et al., “Mobile platform for rapid sub-picogram-per-milliliter, multiplexed, digital droplet detection of proteins”, Proceedings of the NationalAcademy of Sciences, vol. 116, no. 10, 5 March 2019, pages 4489-4495.
Applicant’s claim 1 recite the following.
A method for the quantification of the number of target entities encapsulated in a micro compartment, the method comprising the steps of:
(a) providing a detection molecule comprising
(i) a target binding site specific for the target entity, or at least capable of binding to the target entity,
and (ii) an enzymatic component capable of catalysing a chemical signalling reaction;
(b) bringing into contact the detection molecule and the target entity to allow for a specific binding of the detection molecule to the target entity;
(c) optionally, removing at least any unbound detection molecules;
(d) encapsulating one or more (an unknown number of) target entities bound with detection molecules into one or more micro-compartments together with substrate molecules, wherein the substrate molecule is a substrate of the enzymatic component, and which when brought into contact with the enzymatic component renders the enzymatic component to catalyse the chemical signalling reaction; and
(e) quantifying the detectable signal for each micro compartment and thereby quantifying the number of target entities encapsulated in each micro compartment.
These limitations of Applicant’s claim 1 are disclosed by Yelleswarapu as follows.
Yelleswarapu teaches that digital droplet assays are assays in which biological samples are compartmentalized into millions of femtoliter-volume droplets and interrogated individually. (Page 4489, left column, first full para.)
Yelleswarapu teaches digital droplet-based assays wherein millions of assays in parallel within femtoliter volume droplets are performed. Digital enzyme-linked immunoassays (dELISA) can achieve multiplexing for a broad range of targets. (Page 4489, left column, second full para.)
Yelleswarapu teaches an approach wherein multiplexed dELISA uses microbeads color-coded with different fluorescent dyes, where the color code corresponds to the protein targeted by its antibody. A duplex cytokine assay (GM-CSF and IL6) is performed in serum using UV and green fluorescent beads. (Page 4490, right column, first full para.)
Provided on their chip are:
i) in a microbead processor, microbeads capture their target proteins from serum and are tagged with enzyme labeled immunocomplexes for downstream amplification within droplets, and are iteratively washed between each labeling step
[Examiner notes that this disclosure implies that there is a detection molecule that comprises a target binding site specific for a target entity, or at least capable of binding to the target entity, meeting Applicant’s limitations in subsection (a) of claim 1];
ii) a droplet generator, where the microbeads are mixed with the enzyme’s substrate and encapsulated into water-in-oil droplets;
iii) a 3D microfluidic channel that takes 3.2 min for the droplets to pass, allowing time for the enzymatic amplification of the fluorescent signal; and
iv) a mobile phone-based detector, where the droplets fluorescence are rapidly detected using time domain-encoded optofluidics. (Page 4490, right column, first para. under “Results and Discussion”).
Downstream of the microbead processor, the released microbeads are mixed with the ELISA substrate and encapsulated into droplets suspended in oil. (Page 4491, left column, last, partial para. ).
For each target molecule, the active enzymes per bead is calculated by quantifying the number of droplets that contained a bead and that fluoresced red, normalized to the total number of beads. (Page 4492, right column, first para.)
The assays can measure for example two protein levels (GM-CSF and IL6). (Page 4493, last, partial para.)
Yelleswarapu discloses that while a duplex assay was performed, droplet throughput and multicolor detection can be increased to multiplexing hundreds of markers. (Page 4494, left column, last, partial para.)
As to claim 2, see discussion of Yelleswarapu above with respect to claim 1, regarding quantification and multiplexing with different targets, enzyme labeling and providing enzyme substrate.
As to claim 4, the target entity is a particle (bead) (see discussion of Yelleswarapu above, example, in page 4490, right column, first para. under “Results and Discussion”, and page 4491, left column, last, partial para.)
As to claim 5, see discussion of claim 1 above regarding enzymatic labeling and providing enzyme substrate [for colorimetric reaction).
As to claim 6, see discussion of claim 1 above regarding water-in-oil droplets (e.g., page 4490, right column, first para. under “Results and Discussion”).
As to claim 8, see discussion of claim 1 above disclosing that for each target molecule, the active enzymes per bead is calculated by quantifying the number of droplets that contained a bead and that fluoresced red, normalized to the total number of beads. (Page 4492, right column, first para.)
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.
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yelleswarapu et al., “Mobile platform for rapid sub-picogram-per-milliliter, multiplexed, digital droplet detection of proteins”, Proceedings of the NationalAcademy of Sciences, vol. 116, no. 10, 5 March 2019, pages 4489-4495.
As to claim 7, Yelleswarapu, discussed above (see discussion of claim 1), is silent as to the substrate molecule being encapsulated within each micro compartment in excess to the concentration of the detection molecule in the same micro compartment.
However, as discussed above, Yelleswarapu discloses that microbeads are mixed with the ELISA substrate and encapsulated into droplets suspended in oil. (Page 4491, left column, last, partial para.)
For each target molecule, the active enzymes per bead is calculated by quantifying the number of droplets that contained a bead and that fluoresced red, normalized to the total number of beads. (Page 4492, right column, first para.)
It would have been obvious to one skilled in the art that the substrate molecule that is encapsulated within each micro compartment [droplet] is provided in excess to the concentration of the detection molecule in the same micro compartment since it is well-known and predictable to one skilled in the art that providing the enzyme substrate in excess to the concentration of the detection molecule allows for sufficiently detecting any detection molecules that are present, as would be desirable for quantification of target.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ann Montgomery whose telephone number is (571)272-0894. The examiner can normally be reached Mon-Fri, 9-5:30 PM PST.
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, Greg Emch can be reached at 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Ann Montgomery/Primary Examiner, Art Unit 1678
Prosecution Insights