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 in the reply filed on 4/28/2026 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)).
Claim 23 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4/28/2026.
Claims 1-22 are under consideration in this office action.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on at least page 181, [0674], line 2. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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.
Claim 3 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 3 recites, using the harvested portion of the first gene-edited clonal cell colony in a cell therapy”. However, base claim 1 recite in the preamble, a method of manufacturing gene-edited cells”. A cell therapy administers cells to a subject with the end result of treating the subject. As such, it is not apparent how a method that has the end result in delivery of cell in vivo can be considered a method of manufacturing a gene-edited cell as the preamble of claim 3, by dependency, states. As such, the scope of the claim is not apparent and thus the claim is indefinite.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-12 and 22 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 6, 10, 18 of U.S. Patent No. 11,680,247. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims are an anticipatory species of the instant claims.
Regarding claim 1, patent claim 1 and 18 discloses a method for producing a monoclonal iPSC product. iPSC are considered a species of gene-edited cells because the cells are reprogrammed. For example, patent claim 18 reprogramming arrive at iPSC comprises the of genome editing tools. As such, the method of producing monoclonal iPSC is a species of the instantly claimed method of manufacturing a gene-edited cell. Patent claim 1 discloses input cells are reprogramed in a closed culture cell container (a & b) (i.e. seeding a plurality of gene-edited cells in a culture container). Step b specifies the formation of a plurality of clonal iPSC candidate cells (i.e. culturing the plurality of gene-edited cells into a plurality of gene-edited cell colonies. Patent claim 1 step c acquires using an image sensor image data of the plurality of clonal iPSC colonies emerging from the from the plurality of clonal candidate cells (i.e colonizing the plurality of gene-edited cells by interative specially selective removal of one or more portions from the plurality of gene-edited cell colonies as the colonies proliferate). Step d further uses acquired imaging data to predict clonal functionality and step e selects based upon said prediction (i.e. tracking one or more characteristics of the plurality of gene-edited clonal cell colonies and maintaining the cell density of colonies based on tracked characteristic). Step e selects at least one of the plurality of iPSC colonies (i.e. selecting a first gene-edited clonal cell colony from the plurality of gene-edited clonal cell colonies). Step f removes non-selected colonies from the cell culture chamber using cell editor (i.e. removing the plurality of gene-edited clonal cell colonies except the first gene-edited clonal cell colony). Step g expands the selected iPSC colon in the cell culture chamber (expanding the first gene-edited clonal cell colony). As such, patent claim 1 is an anticipatory species of instant claim 1 and therefore renders it obvious.
Regarding instant claim 2, patent claim 1 does not further at least a portion of the first gene edited clonal cell colony. However, at the time of the patent it would have been obvious to an artisan of ordinary skill to harvest at least a portion of the selected and expanded iPSC clonal colony for further experimental use such a differentiation of the cells. As such, patent claim also renders claim 2 obvious.
Regarding claim 3, patent claim 1 does not further specify using the harvested cell for a cell therapy. However at the time of the patent method of differentiating iPSC for further use in cell therapies had been long established and an obvious use of the harvested iPSC colony.
Regarding claim 4, patent claim 1 teaches iPSC cells as claimed.
Regarding claim 5, patent claim 1 does not teach repeating the expanding and removing of the gene-edited colony as claimed. However, an artisan of ordinary skill would understand the process can be repeated as many times as needed to arrive at an increased amount of clonal iPSC cells. As such, instant claim 5 is an obvious variant of patent claim 1.
Regarding claim 6, patent claim 6 discloses the phenotypic feature comprise a cell morphology or a cell proliferation rate.
Regarding claim 7, patent claim 2 specifies wherein the image data comprises a plurality of time series images of the plurality of clones iPSC candidate cell colonies.
Regarding claim 8, patent claim 1 discloses the expanding and determining cell removal based upon image data characteristics as discussed above.
Regarding claim 9, patent claim 1 teaches selection of first iPSC clonal colony based on image characteristics described above.
Regarding claims 10-12, patent claim 10 discloses an image sensory system and computer processor (in base claim) and a laser radiation.
Regarding claim 22, patent claim 1 does not specify how long the duration of the method is. However an artisan of ordinary skill at the time of the invention predictably arrive at the claimed duration through routine optimization.
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) 1-12 and 21-22 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Kelso (WO2021/150631 pub date:7/29/2021; effectively filed 1/21/2020).
Regarding claim 1, Kelso discloses a method of generating clonal populations of cells by first transfecting the cell (FIG 4). In the case of a CRISRP edit, the "transfection" process may include introduction of one or more nucleic acid molecule(s) that code for one or more Cas protein(s) and/or one or more guide RNA(s) or may include introduction of the one or more Cas proteins themselves and/or one or more guide RNA(s) (e.g., where the guide RNA(s) may be pre-bound to the Cas protein or not pre-bound to the Cas protein(s)). In some instances, e.g., in the case of a CRISPR edit, the "transfection" process may include introduction of multiple guide RNAs, multiple enzymes, multiple DNA repair templates, etc. (p. 14, [0040]). As such the method of Kelso discloses embodiments that use gene-edited cells as claimed. Next, A plurality of individual transfected cells is introduced and allowed to attach to a surface
( e.g., a "growth surface") within the cell selection compartment and are subsequently allowed to undergo several cycles of growth and division in order to form small, clonal cell colonies (FIG 4, p. 38, [0012]). These disclosures disclose the seeding and culture step of claim 1. Super-resolution imaging can be used to monitor attachment, cell growth and, colony formation (p. 39, [0116]). In some instances, imaging may be performed in a manual, semi-automated, or fully automated manner at a frequency of at least once per day, at least twice per day, at least four times per day, at least six times per day, at least twelve times per day, at least twenty four times per day (at least once per hour), or at least once per 30 minutes (p. 40, [00117]), in other words a time series. Impedance measurements at selected frequencies may be used to monitor cell adherence and proliferation properties that are dependent on the characteristics of specific types of cells. These disclosure encompass the clonalizing, tracking and maintaining step set of claim 1. In some instances, the cell selection compartment ( or any other compartment in the disclosed devices or cartridges) may be imaged for the purpose of detecting the positions of cells and/or selecting individual cells or clonal cell colonies for photodetachment, removal for testing, photoablation, and/or expansion to create one or more clonal cell populations for subsequent harvesting. In some instances, images may be viewed live by a skilled operator for identification of cells and manual control of, for example, a photodetachment or photoablation step. In some instances, images may be captured and processed using a semi-automated or fully-automated process to perform one or more of the following steps: (i) image segmentation, (ii) feature extraction, (iii) cell identification and
determination of position coordinates, (iv) cell selection, and (v) transfer of cell position
coordinate data for cells selected for destruction to a targeting system that, e.g., directs a laser scanning system or that controls the position of the translation stage and laser exposure to selectively detach a portion of a selected cell colony or to selectively ablate unwanted cells. (FIG 4, paragraph [0119], pp. 40-41). These disclosure disclose the selecting removing and expanding steps of claim 1. As such, Kelso expressly discloses all the limitations of claim 1.
Regarding claim 2, Kelso discloses further harvesting as discussed above. (paragraph [0119], pp. 40-41.
Regarding claim 3, Kelso discloses Methods and
systems for creating homogeneous clonal cell populations have become increasingly important for a variety of emerging applications including, but not limited to, expression and purification of genetically-engineered proteins, nucleic acids, and other cellular components; production of biologic drugs (biologics); and therapeutic applications of stem cells (p.13, [0031]).
Regarding claim 4, Kelso discloses that the method can be used to prepare a clonal population of iPSC (p. 17, [0050]).
Regarding claim 5, Kelso discloses In some instances, the selected cells or clonal cell clusters may be subjected to repeated cycles of cell growth and division until they reach a specified level of confluence on a surface on which they are grown (p. 52, [0153]).
Regarding claim 6, the selecting is based on a
number of cells within the at least one clonal cell colony, a morphology of cells within the at least one clonal cell colony, a surface density of cells within the at least one clonal cell colony, a growth pattern of cells within the at least one clonal cell colony, a growth rate of cells within the at least one clonal cell colony, a division rate of cells within the at least one clonal cell colony, expression of an exogenous reporter by cells within the at least one clonal cell colony, or any combination thereof (p. 5-6).
Regarding claim 7, the tracking, series image capturing and determining tracked characteristics imaged are disclosed as discussed above.
Regarding claim 8, the maintaining step claimed are as described above in Kelso.
Regarding claim 9, the selecting a first gene-edited colony base on one or more characteristics are disclosed by Kelso as described above.
Regarding claim 10, Kelso discloses the disclosed systems may comprise (i) one of or more of the disclosed devices or cartridges for performing cell transfection, cell selection, and/or cell expansion, (ii) a microscope or other imaging unit (including a light source and one or more image sensors or cameras) that is configured for viewing cells on a surface or within a compartment, e.g., a cell transfection compartment, a cell selection compartment, and/or a cell expansion compartment, (iii) one or more lasers configured for performing photoporation, photodetachment, and/or photoablation (in
some instances, one or more of the lasers may be optically-coupled with an imaging unit objective such that the laser and objective are capable of working in tandem to focus and deliver laser light to a specific location in a compartment), (iv) a laser targeting system (e.g., a translation stage or a laser scanning system) capable of fast and accurate positioning of individual cells at a laser focal point, or of directing focused laser light to a specific position on or near a surface or within a compartment of the disclosed devices or cartridges, (v) one or more processors, controllers, or computers, (vi) image capture and processing software for identifying cells and determining their position coordinates in each of a series of one or more compartments,
(vii) laser targeting control software for controlling laser focus position, laser power, laser pulse frequency, and/or exposure time (dwell time), (viii) system control software for coordinating the
fluid control, image capture, image processing, laser targeting, and laser poration, detachment, and/or ablation steps of the process, (ix) an environmental control chamber or module (e.g., an incubator) that maintains the cells within a device or cartridge under a specified set of cell culture conditions, or (xi) any combination thereof (o. 55, [0163]).
Regarding claims 11 and 12, Kelso discloses In some instances the laser used for photoporation, photodetachment, and/or photoablation of cells in the disclosed methods and systems may produce light having a bandwidth (e.g., full width at half maximum (FWHM)) centered on or near the peak wavelength that ranges from about 0.0001 nm to about 10 nm, depending on peak wavelength and whether
the laser is a continuous wave laser or pulsed laser (p. 59, [0174]).
Regarding claim 21, Kelso discloses embodiments of a cartridge comprising at least one compartment configured for performing cell transfection, cell selection, cell expansion or any combination thereof (p. 2, [0007]). In some embodiments, a wall of the second compartment ( or of at least one compartment) comprises a surface coating or surface treatment to facilitate attachment of adherent cells (p. 3, paragraph [0008]). A such, in this embodiment the cells are adherent continuously in the at least one compartment.
Regarding claim 22, Kelso discloses a prophetic examples that recites ablation 5 days post-seeding to enforce clonality (p. 84, {0214]) exporting cell 8 days after seeding, and allow clone attachment for 4 days post-export (p. 84 {0215}). As such, Kelso disclose a method duration of at least 7 and at least 10 days.
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) 13-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kelso (WO2021/150361 pub date:7/29/2021; effectively filed 1/21/2020), as applied to claims 1-12 and 21-22 above, and further in view of Wang (US2021/0403942 pub date:12/30/2021 effectively filed:11/6/2018).
Regarding claim 13, Kelso does teaches that in some instances, the cell selection/expansion compartments may be configured to include a surface coating layer designed to facilitate cell attachment, or to facilitate laser-based photodetachment or photoablation. Examples include, but are not limited to, a plasma treatment ([0064] and [0067]-[0068]). However, Kelso does not expressly teach the plurality of gene-edited cells a cultured on a laser film.
Wang teaches a system for cell control comprising continuous thin film of absorbing material that is deposited onto the transparent surface of a substrate ([0482]-[0483] and [0491]). Wang discloses the later film is a plasmonic film, has wavelength selective absorption, and is configured to enable light-based cell imaging ([0490]-[0491]). Wang teaches the disclosure also includes laser-based methods to selectively transfer cargo into individual cells, onto individual cells, or to selectively transfer individual cells onto a target surface (“bioprinting”). Material of interest is dispersed in a film over a planar donor substrate, which is disposed facing a receiving substrate. A laser scans the donor substrate, energizing the film resulting in the material being transferred forward onto the receiving substrate. Computer imaging and control provides for precise spatial modulation with respect to both the donor and receiving substrates. Such systems and methods generally provide for cell manipulation using laser-induced forward transfer ([0465]). As such the ordinary artisan would understand that the plasmonic laser film of Wang comprises the same structure as the claimed laser film which serve the purpose of cell removal from a substrate.
As such, it would have been obvious to an artisan of ordinary skill that the laser film of Wang, having the same structure and having the ability to transfer a cell or population of cells (i.e. remove cells from on surface and place them on another) upon later excitation, is applicable to the selection compartment (i.e. compartment for laser cell removal) taught by Kelso to predictably arrive at the limitation of claim 13. An artisan would have a reasonable expectation of success because the laser film of plasmonic and has been used to manipulate cell, such as in cell removal in the process of cell transfer as taught by Wang. Further, an artisan would be motivated to use a plasma film because Kelso teaches that plasma treatments facilitate laser-based photodetachment or photoablation.
Regarding claim 14, Wang teaches the laser film is absorptive from the pulsed layer, thereby removing cells adhered to the laser film as discussed above.
Regarding claim 15, Kelso teaches the pulse laser comprises one or more visible light laser as previously discussed.
Regarding claim 16, Wang teaches the laser film is semi-transparent and have wavelength selective absorption ([0490]-[0491]).
Regarding claim 17, Wang teaches the laser film is plasmonic film as discussed above.
Regarding claim 18, Wang teaches the laser is configured to enable light-base cell imaging ([0490]-[0491]).
Regarding claims 19 and 20, Kelso teaches light based cell imaging is within an imaging wavelength range emitted by the image sensor ([0075]-[0076], [0116], [0168]).
The combination of prior art cited above in all rejections under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales F and G are applicable. The claimed method was known in the art at the time of filing as indicated by Kelso in view of Wang. Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCIA STEPHENS NOBLE whose telephone number is (571)272-5545. The examiner can normally be reached M-F 9-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632
Prosecution Insights