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 .
Claims 1-20 are pending as originally-filed, and are considered herein.
Claim Objections
Applicant is advised that should claim 2 be found allowable, claim 3 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 2 requires the disruption of the cells to further comprise poration of the cells. Claim 3 requires cargo to be delivered while being porated. However, poration is the use of force (typically an electrical field) to deliver something into the cell. Claim 3, simply states that cargo is delivered during poration. However, poration, as stated, delivers cargo. Thus, these claims, despite a slight difference in wording, have substantially the same scope.
Applicant is advised that should claim 12 be found allowable, claim 13 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 12 requires the disruption of the cells to further comprise poration of the cells. Claim 13 requires cargo to be delivered while being porated. However, poration is the use of force (typically an electrical field) to deliver something into the cell. Claim 13, simply states that cargo is delivered during poration. However, poration, as stated, delivers cargo. Thus, these claims, despite a slight difference in wording, have substantially the same scope.
Applicant is advised that should claim 11 be found allowable, claim 15 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).Claim 5 requires a fluid to be inside the container. However, Claim 11 requires the cells to be cultured. Without a fluid medium, the cells could not be cultured. Thus, despite a slight difference in wording, these claims have substantially the same scope.
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 1 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 1 recites “the light source configured to direct laser pulses toward the film”. It is not clear how a light source directs laser pulses. The component (the light source) emits light. How does the light direct the laser pulses?
Claim 1 also recites “the laser pulses selectively target the film to selectively disrupt specific cells”. It is not clear what is being claimed. Is applicant claiming the system, or only the system at the time it is selectively targeting the film?
Claim 1 recites “the film is configured to convert optical energy from the laser pulses into mechanical energy to selectively disrupt the specific cells”. It is not clear how the conversion of energy here causes selective disruption of the specific cells. In fact, the conversion does not selectively target these cells, but the localization of the laser pulses, i.e., the selectively targeting the film to places where target cells are present, which causes disruptions of the targeted cells near the sight of the conversion. The conversion does not then go forth and selectively target the 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.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,643,667. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1: Patent Claim 1 teaches a laser-activated surface, with cells positioned a distance from the surface, and a laser providing pulses that enable import or export of cargo from/to the medium around the cells, and contrast-agent microbubbles. The cells may be stationary, in Claim 4, and thus, are on a surface of the vessel containing the cells. Thus, the cells must be on a surface of a container. Additionally, Claim 15 makes clear the laser-activated surface may comprise a layer of material, which may be considered a film on the surface. Claims 6-7 teach that the laser activation may be spatially targeting the selected cells. Claim 18 teaches that the laser may be absorbed, forming bubbles, and such is necessarily a conversion of laser/optical energy, into mechanical energy. The final piece, that of the laser being exterior to the container, it is argued that the essential written description of the patent teaches that the laser is exterior to the contain (e.g., Figure 21).
Claim 2: poration is taught in Claims 6 and 9, and it is argued that essential to the whole of the claims is that poration occurs, as it is an intracellular-delivery system, and cargo is imported or exported from the cells (e.g., Claim 1).
Claim 3: as argued in the double patenting warning, poration is the movement of cargo into the cells, and Claim 1 of the patent teaches import of cargo.
Claim 4: Claims 1, 10, and 18-20 teach that the system form microbubbles, which by their nature cause such pressure waves and disrupts the cells. Further the essential written description provides the same (e.g., SUMMARY, paragraph 2).
Claim 5: The cells, being in the container, must contain a fluid, otherwise the cells would be dead, and not be able to porated.
Claim 6: Claims 1, 10 and 20 teach contrast agent forming microbubbles.
Claim 7: the contrast agent of Claims 1, 10, and 20 necessarily absorb at a specific wavelength of the laser pulses, or you would not have the microbubbles.
Claim 8: Claim 9 teaches transport of cargo by fluid turbulent flow, which necessarily requires such channel for fluid.
Claim 9: Claim 15 teaches an oxide layer.
Claim 10: Claims 15-16 teach layers for laser absorption, and they must be continuous, or it would not be able to absorb.
Please note: Claims 11-20 are not precluded from NSDP rejections, as the present Application is a CONTINUATION Application of the Patent’s Application. In order to be precluded it is required that the Application be a divisional Application. In keeping with such, claims to both systems and methods are present.
Claims 11-20, as shown above, the structure is present, and thus, the method steps, simply applying the structure is provided by way of the essential written description for the device, in the specification, and thus, for the same reasons as above, the various claimed scopes are obvious. For example paragraph 74 of the patent teaches the use of the films to promote bubble formation in the process of transfecting cells.
The claims are obvious over the patent. The Artisan would make the invention and expect success, as it is claimed subject matter taught for that specific use in the specification.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
As seen by dependent Claims 7 and 17, the claims are generic for the wavelength of the laser pulses being highly absorbed by a generic fluid medium.
The specification provides on recitation of the wavelength being highly absorbed by the medium (p. 18, paragraph 2), which is provided support by way of a single example, i.e., 3 microns, provided by a YAG laser (2940nm), where water is highly absorbed, thereby concentrating the thermal effect in the vicinity of the laser interaction, and isolating the cell from optical interactions (p. 18, paragraph 3). In the same paragraph, it is mentioned other wavelengths that are highly absorbed by water, i.e., 1.5, 2.0, and greater than 10 micrometers (Id.). These same thermal effects are used to promote membrane opening during the laser-activated bubble process (p. 16, last paragraph). No other examples of wavelengths are provided for high absorption which produced this heating effect to promote poration by the substrate.
The concentration of water is what makes it so highly absorbed. The Art recognizes that water is approximately 55.5 molar, i.e., about 99.5% of a medium which allows cells to live and grow, is composed of water. Additionally, the absorption is an optical interaction, which requires higher concentrations for higher absorption. Thus, if another composition were provided that is highly absorbed at a wavelength, the concentration would be so high that the medium the cells were in, would not allow the growth of the cells. For example, if benzene were utilized (absorbed at 178-208nm and 230-276nm), it would kill the cells even at low concentrations (e.g., Sun, et al. (2021) “Toxicity in hematopoietic stem cells from bone marrow and peripheral blood in mice after benzene exposure: Single-cell transcriptome sequencing analysis”, Ecotoxicology and Environmental Safety, 207: 111490, 12 pages long, see ABSTRACT). Finally, if the laser is completely absorbed or so-highly absorbed, there is no reason to believe the film would convert optical energy to mechanical energy and perform its purpose according to the claims.
Considering the widely ranging wavelengths distinct compounds may absorb, and the levels of compound needed in the medium to absorb, and the high toxicity of many compounds at these levels, combined with the single showing of water with microwaves, the water being present and non-toxic at 55.5M, the Artisan would not reasonably understand Applicant to have been in possession of a generic highly-absorbed component in the medium for a generic wavelength.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-4, 9-14, and 19-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims, as seen by depending claims 5 and 15, are generic for systems with cells do not contain a fluid medium.
The specification discloses that the purpose of these systems and methods is for intracellular delivery and extraction from cells (e.g., Summary, paragraph 1). Such is done in the presence of medium which contains molecules to be transfected, and medium in which the molecules are removed (e.g., Figures 1-13). There is no disclosure how to transfect cells without a fluid media, containing water.
It is well known that cells, without a medium would die and dry out, and thus, these same molecules would be not be possible to enter the cells, or leave the cells, as there is no medium to carry out such entry/exit, and the cells would be dried out and unable to perform such transfection or emission of internal components.
Thus, at the time of invention, the Artisan would not have understood Applicant to have been in possession of the systems and methods without a liquid medium maintaining the cells.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
As seen by separately-depending claim 6, the claims are generic for microbubbles formed of contrast agent being in the fluid medium.
The specification teaches that methods may include contrast agent and generating microbubbles and collapsing the same (e.g., p. 4, paragraph 4). Figures 19 and 20 show optical pulse causing microbubble formation, and the exapansion and collapse of these causes pressure waves, causing secondary bubbles to form.
However, this secondary formation is not what is claimed, as Claim 6 teaches contrast-agent microbubbles. Thus, the contrast agent microbubbles are in the medium and would no selectively disrupt specific cells, as it is diffused and subject media flow.
The Art does not teach how contrast agent can specifically target the cells when present in the medium.
Thus, the Artisan would not understand Applicant to be in possession of a generic contrast agent in the medium, for selectively disrupting cells.
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) 1-5, 7, 9-15, 17, and 19-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Courvoisier, et al. (2015) “Plasmonic Tipless Pyramid Arrays for Cell Poration”, NanoLetters, 15: 4461-66.
Claims 1-3 and 11-13: Courvoisier teaches a gold-film on a pyramid array (e.g., Figure 1). The same was utilized where HeLa cells are seeded on the substrate and grown to confluency (e.g., pp. 4464-65, paragraph bridging). An external laser was utilized to selectively porate (i.e., disrupt) and transfect specific cells, i.e., the upper half of cells in Figures 9A-9D.
Claim 4 and 14: as the microbubbles are formed (e.g., p. 4464, col. 2, paragraph 3), it is presumed that such forms the pressure wave disrupting the cells, through the formation and contraction of the microbubbles created.
Claims 5 and 15: as the cells are grown to confluency, and they transfected by Calcein fluorescent probes, there is necessarily a fluid medium in the container.
Claims 7 and 17: a wavelength of 800nm is utilized (e.g., ABSTRACT) and the water based medium the cells is in absorbs highly at this wavelength.
Claim 9 and 19: a gold film is utilized (e.g., Figure 1A), which is necessarily a metallic film.
Claim 10 and 20: the gold film is continuous, covering the whole region of the cells (e.g., Figure 1).
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.
Claim(s) 1-5, 7-15, and 17-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Courvoisier, et al. (2015) “Plasmonic Tipless Pyramid Arrays for Cell Poration”, NanoLetters, 15: 4461-66, as applied to claims 1-5, 7, 9-15, 17, and 19-20, above, and further in view of Lee, et al. (2007) “Microfluidic System for Automated Cell-Based Assays”, JALA, 12(6): 363-67.
As shown above, the various claims are anticipated by Courvoisier alone, and thus, is also obvious over the same. However, the aspect of channels for delivery of media and removal of old media, is not taught.
On the other hand, this is well known in the art. In fact, Lee teaches the same in another advanced system for delivery and removal of media (e.g., Section “96-Well Plate Interface” on page 364). Such is taught for delivery and removal of media.
Thus, at the time of invention, it would have been obvious to modify Courvoisier to utilize an inlet and outlet for flow of media through the culture chamber. The Artisan would do so to feed the cells, and would expect success, as it has been known in the art for such use for years.
Claims Free of the Art
Claims 6 and 16 are free of the art of record. To wit, the Art, as shown by Courvoisier in the rejections above, focuses on utilizing the substrate and film to form microbubbles, for selective disruption of cells. However, the presence of contrast agent in the fluid, which causes microbubbles upon laser irradiation would not be selective, as it is in the fluid, and as such would diffuse to any other cells, thereby causing the system to not be selective. It should be noted, however, this same reasoning causes a written description rejection on these same claims.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT M KELLY whose telephone number is (571)272-0729. The examiner can normally be reached M-F: 8a-5p.
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ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638