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 .
Election/Restrictions
Applicant’s election of Group I (claims 1, 2, 10-12, 14, 22, 26, 28, 82 and 83 in the reply filed on March 25, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 31, 34, 42-44, 52, 58 and 98 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim.
Claims 1, 2, 10-12, 14, 22, 26, 28, 82 and 83 are pending and examined below.
Priority
The present application is a 35 U.S.C. 371 national stage filing of the International Application No. PCT/US2022/028546, filed May 10, 2022. Applicant’s claim for the benefit of a prior-filed parent provisional application 63/186,651 filed on May 10, 2021 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is May 10, 2021.
Claim Objections
Claim 82 is objected to because of the following informalities: the claim recites “ce11” instead of “cell”. 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 1, 2, 10-12, 14, 22, 26, 28, 82 and 83 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 1 and 11 recite, “…through a plurality to constrictions under one or more parameters.” The language “under one or more parameters” is unclear – what exact further limitation does this language provide? Is the passing of the cell suspension through a plurality of constrictions enough, or must “one or more parameters” be met? And if those parameters must be met, what are they?
Dependent claims 2, 10, 12, 14, 22, 26 and 28 are rejected on the same basis as claim 1, as none of these claims provide further information for understanding what the necessary “parameters” are.
For the purposes of examination, this limitation is interpreted as not reciting the “under one or more parameters”.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 10 recites the broad recitations less than about an hour, and the claim also recites less and 50 minutes, 40 minutes…and less than 1 second which is the narrower statement of the range/limitation. Claim 12 recites the broad recitations at least 1-fold, and the claim also recites 2-fold, 3-fold…50-fold which is the narrower statement of the range/limitation. Claim 26 recites the broad recitations less than about 5 days, and the claim also recites less than 1 day, less than 1 hour, less than 1 minutes, less than 1 second, and less than 1 µs which is the narrower statement of the range/limitation.
Claim 83 recites the broad recitations (1) at least about 1 x 103 cells/mL, and the claim also recites at least about 1 x 104, 1 x 105, 1 x 106…at least about 1 x 109 which is the narrower statement of the range/limitation; (2) at least about 1psi, and the claim also recites at least about 2 psi, 3psi,…at least about 150 psi which is the narrower statement of the range/limitation; (3) at least about 20% and the claim also recites at least about 30%, about 40%…at least about 99% which is the narrower statement of the range/limitation; (4) the length of the constriction is about 1 µm and the claim also recites at least about 5 µm, about 10 µm…and about 100 µm which is the narrower statement of the range/limitation; (5) the width of the constriction is about 2 µm, and the claim also recites at least about 3 µm, about 4 µm…and about 10 µm which is the narrower statement of the range/limitation; and (6) the depth of the constriction is at least about 1 µm and the claim also recites at least about 2 µm, about 3 µm…and about 120 µm which is the narrower statement of the range/limitation;
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 82 is indefinite as it recites “…surface property of the constriction (e.g. roughness, chemical modification, hydrophilic, hydrophobic). It is unclear if these “e.g.” recited elements are merely exemplary or if the limitation is intended to limit to only those recited.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1, 2, 10-12, 14, 22, 26, 28, 82 and 83 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu (Georgia Instit Tech, 2020).
The claims are directed to methods of delivering a payload to a nucleus of a cell including passing a cell suspension including a cell and a payload through a plurality of constrictions which allows the payload to enter the cell and be delivered to the nucleus.
Liu teaches cell volume exchange for convective transfer (VECT) to intracellularly deliver molecules and particles to cells, including larger macromolecules. (entire doc, esp. pg. 22). The VECT procedure involves flowing cells through a microfluidic channel with ridges with multiple rectangular cross-sections, thereby constricting the cells and enabling the cell to exchange intracellular fluid with fluid outside the cell, resulting in delivery of desired molecules to the cell. (pg. 22, pg. 29, Fig. 3.1). With respect to independent claim 1, Liu teaches that cell VECT delivers payloads to the nucleus of the cell (pg. 71, “…it is more advantageous for a majority of applications since it allows direct access to various intracellular interaction sites of interest, such as the nucleus, ribosomes, cytoskeleton and organelles”, Fig. 4.5 (delivery of 2000 kDA TRITC-dextran to the nucleus).
With respect to claims 2 and 14, Liu teaches delivery of EGFP mRNA to K562 cells, enabling the cells to express an exogenous gene; (pg. 102-103, Fig. 5.3); delivery of precomplexed CRISPR-Cas9 RNPs enabling permanent knockout of a target gene (pg. 104-106).
With respect to claim 10, Liu teaches that less than an hour after cell VECT delivery of Cy5-mRNA to K562 cells, confocal imaging demonstrated that the delivery had been completed. (pg. 71-72, Fig. 4.5).
With respect to claim 11 and 12, Liu teaches that multiple ridges (constrictions) allow greater delivery of the payload, than a single ridge and increase the delivery efficiency at least about 1-fold. (pg. 49-50, “More Compressions Increases Delivery”).
With respect to claim 22, Liu teaches the plurality of ridges (constrictions) are within a single microfluidic chip. (pg. 22, pg. 29, Fig. 3.1).
With respect to claim 26, Liu teaches higher flow rates produce better results and that cells’ uptake is best when there is a pause (around 0.5 sec) after the compression, well within the claimed range. (pg. 128-129).
With respect to claim 28, Liu teaches that each of the plurality of the constrictions is the same. (pg. 29, Fig. 3.1).
With respect to claims 82 and 83, Liu teaches these parameters, such as determining the optimized cell size, device characteristics, (magnitude and number of compressions), cell density, flow rate, and payload concentration. (whole doc, see pgs. 23-24, “Aim 1: Governing Parameters of Cell VECT”)
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TERESA E KNIGHT whose telephone number is (571)272-2840. The examiner can normally be reached Monday-Friday 9-4.
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, Maria Leavitt can be reached at 571-272-1085. 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.
/TERESA E KNIGHT/ Primary Examiner, Art Unit 1634
Prosecution Insights