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
Status of Claims
Claims 1-22 are pending. Claims 1-6 are the subject of this NON-FINAL Office Action. This is the first office action on the merits.
Election/Restrictions
Applicants’ election without traverse of Group I (Claims 1-6) in the reply filed on 07/28/2026 is acknowledged. The species election is withdrawn. Claims 7-22 are withdrawn as directed to unelected Group II.
Claim Note
Applicants’ invention is MIC-Drop; the Examiner strongly encourages Applicants to claim this invention. An emulsion droplet with CRISPR and a barcode is not an allowable invention, nor is this Applicants’ invention.
Claim Rejections - 35 USC § 112- Indefiniteness
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.
Claims 1-6 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 pre-AIA the applicant regards as the invention.
In claim 1, the metes and bounds of two critical phrases are unclear. First, the “ gene editing system” is unclear. The specification merely states that “the gene editing system may be a Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated proteins (CRISPR-Cas) system, a transcription activator like effector nuclease (TALEN) system, or a zinc finger nuclease (ZFN) system” (para. 0008). However, critically, the specification never defines what minimal components are required for these “systems”; or “associated proteins.”
Second, “barcode oligonucleotide” is vaguely and confusingly described as “a short sequence of nucleotides (for example, DNA or RNA) that is used as an identifier for an associated molecule, such as a target molecule and/or target nucleic acid, or as an identifier of the source of an associated molecule, such as a cell-of-origin,” or “may also refer to any unique, non-naturally occurring, nucleic acid sequence that may be used to identify the originating source of a nucleic acid fragment” (para. 0099). In other words, any sequence of any nucleic acid. It is impossible to determine from this very generic, vague and confusing description how this “barcode” is distinguishable from the prior art sequences.
Claims 3 and 5 recite trademarked items (3M™ Novec™ 7500, Bio-Rad Droplet Generation Oil for Probes, 008-Fluorosurfactant, Pico-Surf™), not compositions themselves; thus, it is not clear what are the compositions.
Claim Rejection - 35 USC § 112 – Written Description
The following is a quotation 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.
Claims 1-6 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claims contain 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, at the time the application was filed, had possession of the full scope of the claimed invention.
The specification fails to demonstrate possession of all possible “gene editing systems”; or all possible “barcode oligonucleotides.” Instead, the specification discloses a single species of each. For the “gene editing systems,” nucleases. For the “barcode oligonucleotides,” this:
PNG
media_image1.png
288
826
media_image1.png
Greyscale
However, as to the “barcode,” the actual barcode used is never disclosed. Figure 1 (and Figure 2) fail to show any barcodes; T7, SP6 and spacer sequences are not known “barcodes.” Nor do the examples provide any explanation of what barcodes were used. Instead, the specification generically states that any barcode sequences can be used (para. 0099). Yet, even here, no details in relation to the claimed droplet composition (directed to the actual “MIC-Drop” invention) are disclosed. For example, what barcodes work, or are essential, within this “MIC-Drop” context? How are the barcodes designed? Where are the barcodes located in the above oligonucleotide? This lack of detail at the precise point of supposed novelty fails to meet Applicants’ burden to provide “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.”
In sum, a single, vague species fails to satisfy written description for a generic component.
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:
Novelty; Prior Art.—A person shall be entitled to a patent unless—
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; or
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..
Claims 1-6 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by REGEV (US 20190085324).
As to claim 1, REGEV teaches a water-in-oil droplet comprising:
an aqueous phase comprising a gene editing system and a barcode oligonucleotide (emulsion droplet with CRISPR and barcode; Fig. 81); and
an oil phase comprising an oil and a surfactant;
wherein the aqueous phase is encapsulated by the oil phase (id.)
As to claim 2, REGEV teaches the gene editing system is a Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated proteins (CRISPR-Cas) system, a transcription activator like effector nuclease (TALEN) system, or a zinc finger nuclease (ZFN) system (id.)
As to claim 3, REGEV teaches the oil is 3M™ Novec™ 7500, Bio-Rad Droplet Generation Oil for Probes, or a polysiloxane (e.g. para. 0309, 0314).
As to claim 4, REGEV teaches the oil phase comprises from about 90% to about 99.9% of the oil (id.)
As to claim 5, REGEV teaches the surfactant is 008-Fluorosurfactant, Pico-Surf™, or a dendronized fluorosurfactant (id.)
As to claim 6, REGEV teaches the oil phase comprises from about 0.1% to about 10% of the surfactant (id.)
Claims 1-6 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by BLAINEY (US20190049434).
As to claim 1, BLAINEY teaches a water-in-oil droplet comprising:
an aqueous phase comprising a gene editing system and a barcode oligonucleotide (emulsion droplet with CRISPR and barcode; para. 0131- “Non-limiting examples of methods to evaluate response to exposure to a plurality of conditions can be found at US Provisional Patent Application entitled “Systems and Methods for Droplet Tagging” filed Sep. 21, 2012. Accordingly, in or as to the invention it is envisioned that there can be the dynamic generation of molecular barcodes (e.g., DNA oligonucleotides, fluorophores, etc.) either independent from or in concert with the controlled delivery of various compounds of interest (drugs, small molecules, siRNA, CRISPR guide RNAs, reagents, etc.).”); and
an oil phase comprising an oil and a surfactant;
wherein the aqueous phase is encapsulated by the oil phase (id.)
As to claim 2, BLAINEY teaches the gene editing system is a Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated proteins (CRISPR-Cas) system, a transcription activator like effector nuclease (TALEN) system, or a zinc finger nuclease (ZFN) system (id.)
As to claim 3, BLAINEY teaches the oil is 3M™ Novec™ 7500, Bio-Rad Droplet Generation Oil for Probes, or a polysiloxane (para. 0131).
As to claim 4, BLAINEY teaches the oil phase comprises from about 90% to about 99.9% of the oil (id.)
As to claim 5, BLAINEY teaches the surfactant is 008-Fluorosurfactant, Pico-Surf™, or a dendronized fluorosurfactant (id.)
As to claim 6, BLAINEY teaches the oil phase comprises from about 0.1% to about 10% of the surfactant (id.)
Claims 1-2 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by PURAM (US20200071773).
As to claim 1, PURAM teaches a water-in-oil droplet comprising:
an aqueous phase comprising a gene editing system and a barcode oligonucleotide (emulsion droplet with CRISPR and barcode; paras. 0178-81); and
an oil phase comprising an oil and a surfactant;
wherein the aqueous phase is encapsulated by the oil phase (id.)
As to claim 2, PURAM teaches the gene editing system is a Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated proteins (CRISPR-Cas) system, a transcription activator like effector nuclease (TALEN) system, or a zinc finger nuclease (ZFN) system (id.)
Claims 1-6 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by BELHOCINE (US 20190361010).
As to claim 1, BELHOCINE teaches a water-in-oil droplet comprising:
an aqueous phase comprising a gene editing system and a barcode oligonucleotide (emulsion droplet with CRISPR and barcode; paras. 0833-34, 0845, 0865 and Fig. 85); and
an oil phase comprising an oil and a surfactant;
wherein the aqueous phase is encapsulated by the oil phase (id.)
As to claim 2, BELHOCINE teaches the gene editing system is a Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated proteins (CRISPR-Cas) system, a transcription activator like effector nuclease (TALEN) system, or a zinc finger nuclease (ZFN) system (id.)
As to claim 3, BELHOCINE teaches the oil is 3M™ Novec™ 7500, Bio-Rad Droplet Generation Oil for Probes, or a polysiloxane (paras. 0196, 0216, 0292).
As to claim 4, BELHOCINE teaches the oil phase comprises from about 90% to about 99.9% of the oil (id.)
As to claim 5, BELHOCINE teaches the surfactant is 008-Fluorosurfactant, Pico-Surf™, or a dendronized fluorosurfactant (id.)
As to claim 6, BELHOCINE teaches the oil phase comprises from about 0.1% to about 10% of the surfactant (id.)
Prior Art
The following prior art also teaches droplets with CRISPR systems and barcodes: US 20190300868; US 20180340172; WO 2020102610; US 20220002789; US 20220073987; US 20250043366; US 20220119871.
The following prior art also teaches dendronized Fluorosurfactant droplets: Chowdhury, et al., “Dendronized Fluorosurfactant for Highly Stable Water-In-Fluorinated Oil Emulsions With Minimal Inter-Droplet Transfer of Small Molecules,” Nature Communications, (2019) 10:45-46; https://doi.org/10.1038/s41467-5.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Aaron Priest whose telephone number is (571)270-1095. The examiner can normally be reached 8am-6pm.
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, Gary Benzion can be reached at (571) 272-0782. 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.
/AARON A PRIEST/Primary Examiner, Art Unit 1681
Prosecution Insights