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 .
Applicants’ reply to the December 23, 2024 Office Action, filed March 13, 2025, is acknowledged. Claims 1-13 remain withdrawn from consideration, as being directed to a non-elected invention. Applicants cancel claims 18-24 and 26-28, amend claim 14, and add new claims 29-37. Claims 14-17, 25, and 29-37 are under examination.
Any rejection of record in the previous office actions not addressed herein is withdrawn. New grounds of rejection are presented herein that were not necessitated by applicant’s amendment of the claims since the office action mailed December 13, 2024. Therefore, this action is not final.
Information Disclosure Statement
The Information Disclosure Statements filed March 13, 2025 and April 17, 2026 have been considered.
Specification
The use of the terms TALEN® at page 24, line 19 and page 29, line 10; TRANSFECTAM® at page 41, line 23; LIPOFECTIN® at page 42, line 23; HISEQ® at page 45, line 3; MISEQ® at page 45, line 3; NEXTSEQ® at page 45, line 3; MINISEQ® at page 45, line 3; ISEQ 100® at page 45, line 3; and PIGGYBAC® at page 49, line 31; page 51, line 15; and page 54, line 16; which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 15-17, 30, and 34 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.
At claim 15, lines 1-2, it is not clear what is meant by the phrase “partially absorbs laser pulses.” Is there are particular level of absorption that is required to be absorbed in order to remove the selected cells? The specification does not define “partially.” Nor is there any level of absorption that is described in the specification.
Claims 16-17 depend from claim 15, and are therefore included in this rejection.
At claim 30, the term “cell expression” is indefinite. It is not clear if this means expression of genetic material by the cell, and if so, if there are requirements as to which genetic material is expressed by the cell.
At claim 34, line 1, it is not clear what is meant by the phrase “partially absorbing layer.” Is there are particular level of absorption that is required to be absorbed in order to remove the selected cells? The specification does not define “partially.” Nor is there any level of absorption that is described in the specification.
Claim Rejections - 35 USC § 103
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 14, 25, 29-30, 33-34, and 36-37 are rejected under 35 U.S.C. 103 as being unpatentable over Schindler et al. (U.S. Patent Application Publication No. 2004/0077073, published April 22, 2004, and cited in the Information Disclosure Statement filed September 13, 2021) in view of Matsubara (U.S. Patent Application Publication No. 2017/0081628, published March 23, 2017, and cited in the Information Disclosure Statement filed September 13, 2021).
Regarding claim 14, Schindler discloses materials and methods for interactive micromanipulation of biological materials biological materials such as cells (paragraph [0034]). Schindler that it is possible to modify growing cell populations to maintain specific ratios between cell types, introduce specific geometrics between cell types, as well as removing undesirable cells (usually fibroblasts) comprising disposing cells on a substrate, which is interpreted as controlling cell density through removal of unwanted cells (paragraph [0118]). Schindler discloses a structure (102) which supports and positions a matrix and biological material, which is supported on the matrix (paragraph [0045]). Schindler discloses a viewing system comprising an inverted microscope for observing the biological material (e.g., a heterogeneous population of cells) on a platform, which is interpreted as high resolution imaging of cells (paragraph [0073]). Schindler discloses that a pulse of high intensity laser beam can be applied, which can destroy unwanted materials (paragraph [0080]). Schindler discloses that an infrared laser beam is scanned across the cell culture to avoid selected cells (paragraph [0122]). Schindler discloses that focusing the light source onto specific regions of the matrix such that the light is absorbed and converted to heat causing disruption of the matrix and the cells on the matrix, at the point where the light contacts the matrix, which is interpreted as manufacture of desired cells (paragraph [0010]). Schindler discloses that examination by one of any effective optical means can be conducted either by direct observation through the eyepieces, or by images captured by a digital camera or other electronic image capture device and viewed on a monitor, and the desired cells can be identified (Example 4).
Regarding claim 15, Schindler discloses that the biological material matrix comprises an admixture of a thermoplastic polymer and the light-absorbing material, which is interpreted as partially absorbing layer (paragraph [0051]). Schindler discloses that the light absorbing material selectively absorbs light, which is interpreted as partially absorbing (paragraph [0048]).
Regarding claim 29, Schindler discloses that the biological materials can be cell cultures and tissues, which are interpreted as including three dimensional structures (paragraph [0034]).
Regarding claim 33, Schindler discloses that the substrate comprises and absorbing later between the surface of the substrate and the pulsed laser scanner (paragraphs [0007]-[0010] and Figures 1 and 11).
Regarding claim 34, Schindler discloses that the light absorbing material selectively absorbs light, which is interpreted as partially absorbing (paragraph [0048]).
Regarding claim 35, Schindler discloses that the light-absorbing material of can be a metal (paragraph [0049]).
Regarding claim 36, Schindler discloses that the wavelength can be between 300 to about 800 nm (paragraph [0048]). Schindler discloses that the absorbing layer can absorb at wavelengths of about at least 600 nm (paragraph [0008]).
Regarding claim 37, Schindler discloses that the light absorbing material (i.e., the substrate) does not kill or otherwise affect the biological materials, which is interpreted as not leaching or ablating into the cells (paragraph [0049]).
Schindler fails to explicitly disclose or suggest computing cell characteristics to identify cells for removal. Schindler fails to disclose or suggest that the laser pulses convert optical energy into microbubble formation, which destroys/removes selected cells.
Regarding claim 14, Matsubara discloses teaches cell evaluation by image acquisition of a cell group (abstract). Matsubara discloses that the cell evaluation assigns identification information to an evaluation target region (paragraph [0124]).
Regarding claims 25 and 30, Matsubara discloses that computing cell characteristics comprises performing an analysis on data received from a plurality of sources, which shows the processor receiving data that provides for selective identification of cells relating to cell type and differentiation (paragraphs [0113] and [0135] and Figure 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to compute cell characteristics from the images to identify selected cells, as disclosed by Matsubara, in the method disclosed Schindler to evaluate individual cells in a cell image obtained by imaging a cell group, so that the desired (and undesired) cells can be identified and either collected or removed, including those three dimensional cell structures disclosed by Schindler. One of ordinary skill in the art would have been motivated to use the method disclosed and suggested by Schindler and Matsubara because the method provides a way to obtain desired cells, while removing undesired cells.
Claims 15 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Schindler in view of Matsubara, as applied to claims 14-15, 25, 30, 33-34, and 36-37 above, and in further view of Mazur et al. (PCT Patent Application Publication No. WO 2016/127069, published August 11, 2016, and cited in the Information Disclosure Statement filed September 13, 2021).
Schindler and Matsubara disclose and suggest a method of manufacturing cells, as discussed above.
Schindler and Matsubara fail to disclose or suggest that the optical energy is converted into microbubble formation.
Regarding claim 15, Mazur discloses methods and structures for transfecting cells (abstract). Mazur discloses that metal-coated nanocavity matrices can be sued to deliver calcein and dyes into cells using laser pulses (paragraph [0100]). Mazur discloses that bubbles form on the gold-coated nanocavity structured matrices at a laser fluence of approximately 30.8 mJ/cm2, which is interpreted as teaching a coating layer of the substrate absorbs laser pulses to convert optical energy into microbubble formation and that gold is a light absorbing material (paragraph [0100]).
Regarding claim 35, Mazur discloses that bubbles form on the gold-coated nanocavity structured matrices at a laser fluence of approximately 30.8 ml/cm2, which is interpreted as teaching a coating layer of the substrate absorbs laser pulses to convert optical energy into microbubble formation and that gold is a light absorbing material (paragraph [0100]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the gold of Mazur to serve as the metal (light-absorbing material) in the method of Schindler and Matsubara because Mazur’s gold provides a light-absorbing material that can convert optical energy into microbubble formation upon laser pulsing. One of ordinary skill in the art would have been motivated to use Mazur’s gold in the method of Schindler and Matsubara because metal is a well-known substrate for using laser pulses to identify cells and to select a desired cell type, as well as undesired cell types.
Claims 16-17 and 31-32 are rejected under 35 U.S.C. 103 as being unpatentable over Schindler in view of Matsubara and Mazur, as applied to claims 14-15, 25, 30, and 33-37 and further view of Lukianova-Hleb et al. (7(11) International Journal of Medical, Health, Biomedical, Bioengineering and Pharmaceutical Engineering 677-681 (2013), and cited in the Information Disclosure Statement filed September 13, 2021).
Schindler, Matsubara, and Mazur disclose and suggest a method of manufacturing cells, as discussed above.
Schindler, Matsubara, and Mazur fail to disclose or suggest that the microbubbles destroy and remove the selected cells. Schindler, Matsubara, and Mazur fail to disclose or suggest removal of three dimensional colonies.
Regarding claims 16-17 and 31-32, Lukianova-Hleb discloses destroying selected cells with the microbubble formation by optical detection, trans-membrane injection of molecular cargo to and the immediate destruction (i.e., removal) of specific target cells with high speed and selectivity (Introduction). Lukianova-Hleb discloses that cell-specific processing, including gene transfer (abstract).
It would have been obvious to one of ordinary skill in the art to utilize the bubble disclosed by Lukianova-Hleb in the method of Schindler, Matsubara, and Mazur, in order to offer simultaneous multifunctional cell-specific processing with high rate, which provides for transformation of selected cells along with destruction/removal of selected and undesired cells. One of ordinary skill in the art would have been motivated to have multifunctional cell-specific processing with high rate in a method already directed to cell-specific processing, which includes destruction and removal of undesired cells and transformation of remaining desired cells.
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.
Claim 14 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 18 of U.S. Patent No. 12,344,855.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘855 patent and the instant application claim methods for cell culture using imaging and laser pulses to selectively remove undesired cells.
Regarding claim 14, the ‘855 patent claims culturing two populations of cells and selectively removing cells from the second population using an optical subsystem (claim 18). The ‘256 application claims that the optical subsystem is a laser system for removal of selective cells (claim 18).
Therefore, the claims are not deemed to be patentably distinct.
Claims 14 and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12-14, and 16 of copending Application No. 19/216,256 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘256 application and the instant application claim methods for cell culture using imaging and laser pulses to selectively remove undesired cells.
Regarding claim 14, the ‘256 application claims culturing two populations of cells and selectively removing cells from the second population using an optical subsystem (claim 12). The ‘256 application claims that the optical subsystem is a laser system for removal of selective cells (claim 13).
Regarding claim 25, the ‘256 application claims the pulsed laser is operated by a computer system, which can use a computing system to identify cells to be selectively removed.
Therefore, the claims are not deemed to be patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Amendments and Arguments
Regarding the rejection under 35 U.S.C. § 112(a)/first paragraph, Applicants canceled claims 26-28. Therefore, this rejection is withdrawn. However, new rejections under 35 U.S.C. § 112(b)/second paragraph are set forth above.
Regarding the rejections under 35 U.S.C. § 103, Applicants’ arguments have been fully considered but are not deemed to be persuasive. It is noted that the rejections set forth above have been modified.
Applicants assert that neither Schindler nor Matsubara disclose each and every claim limitation of independent claim 14. Specifically, Applicants assert that neither reference discloses removal of cells that controls cell density on the substrate.
To begin, as discussed above, Schindler discloses Schindler that it is possible to modify growing cell populations to maintain specific ratios between cell types, introduce specific geometrics between cell types, as well as removing undesirable cells the pulsed laser scanner. Such removal of undesirable cells will naturally have control over the cell density on the substrate. And Matsubara provides for selective identification of cells relating to cell type and differentiation, which information can be used in the method of Schindler for removal of undesired cells and provides the cell characteristics for cell identification, as required by claims 14 and 25.
Further, it appears that Applicants are attacking each reference individually. However, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Here, it is the combination of Schindler and Matsubara (along with Mazur and Lukianova-Hleb) that disclose the claimed invention, when taken together and as a whole.
Regarding Mazur, it is noted that Mazur is not applied against claim 14. And regarding claim 15, Mazur provides the motivation and disclosure to use microbubbles created by the laser and the gold substrate in order to destroy and/or remove the unwanted cells, as discussed above. Thus, the combination of Schindler, Matsubara, and Mazur, taken together and as a whole, render claims 15 and 35 obvious.
Regarding Lukianova-Hleb, Applicants merely assert that the references do not disclose each and every element of claim 14, or claims 16-17. However, as discussed above, Lukianova-Hleb is applied only to claims 16-17 (as well as new claims 31-32). As such, and contrary to Applicants’ assertions, the combination of Schindler, Matsubara, Mazur and Lukianova-Hleb would lead one of ordinary skill in the art directly to the claimed invention.
Applicants have not provided any objective, factually supported evidence that the instantly claimed invention is not rendered obvious over Schindler in view of Matsubara (and Mazur and Lukianova-Helb). Applicants have provided only arguments of counsel, and arguments of counsel cannot take the place of factually supported objective evidence. See, e.g., In re Huang, 100 F.3d 135,139-40, 40 USPQ2d 1685, 1689 (Fed. Cir. 1996); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984).
For all these reasons, and those listed above, the combination of Schindler in view of Matsubara (and Mazur and Lukianova-Helb) is deemed to render the instant invention obvious.
Regarding the non-statutory double patenting rejection over U.S. Patent No. 11,643,667, Applicants’ amendments and arguments have been fully considered, and are deemed to be persuasive.
In particular, while the instant application is directed to a method for cell manufacturing requiring removal of selected cells using a laser pulse, the ‘667 patent is directed to a system using laser pulses to export or import cargo from cells. Therefore, this rejection is withdrawn. However, new non-statutory double patenting rejections over U.S. Patent No. 12,344,855 and U.S. Patent Application No. 19/216,256 are set forth above.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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, NEIL HAMMELL can be reached at (571) 270-5919. 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.
NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636
Prosecution Insights