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 .
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: “editing subsystem” in claims 1-12; “cell culture system”, “editing subsystem”, “computing subsystem” in claims 13-24; and “cell culture system”, “editing subsystem” in claims 14-18.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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 14-18 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 14-18 recites the limitation "The culture system" in line 1. There is insufficient antecedent basis for this limitation in the claim. One of ordinary skill cannot know which culture system is being referred to. Claims 14-18 recite “The culture system”, but directly or indirectly depend from “method” of claim 1 instead of “system” claim 13. The dependency of claims 14 and 15 should be corrected to depend from claim 13.
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) 1-3, 6-15, and 18-24 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/033871 (Madrid) in view of WO 2021/150631 (Kelso).
As per claim 1, Madrid teaches a method for long term management of a cell culture, comprising (limitations only present within the preamble are interpreted as intended use and are not required;
Page 5, last para: “cycles of exposure to selected minimum numbers of effectors can continue as necessary until an endpoint is achieved.”;
Page 27, first para:
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initializing a cell culture in a (Madrid:
page 19, last para: “The workflow in FIG 5 depicts how image-based laser-scanning could be used to keep various populations or colonies of cells separate within a single sample, well, or cell culture dish”;
page 18, para 1: “cells are in contact with the laser-activated construct, as shown in FIG. 2, in the case where cells 201 are cultured directly on the laser-activated surface 202. In other embodiments, during imaging the cells may be resting on a commonly used cell culture surface, such as glass, polystyrene, or polystyrene coated with a biological matrix.”;
page 35, second to last para: “The cells are plated onto 384 well plates that are fitted with an optically clear substrate that has regularly spaced optical absorption/ bubble nucleation sites on the well-facing surface, for example patches of metallic absorber with a sufficiently rough top surface to promote microsecond bubble nucleation upon exposure to a short laser pulse.”;
Fig. 2(shown below): mainly 201, 202;
Fig. 11(shown below);
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);
acquiring, using an image sensor, time-series image data of the plurality of cell colonies (Madrid: page 17, last para: “FIG. 1 shows a flowchart of a representative workflow. Imaging of cells 5101 may take place while cells are in contact with the laser-activated construct, as shown in FIG. 2, in the case where cells 201 are cultured directly on the laser-activated surface 202.”;
Fig. 1 (shown below): mainly 5101;
Figs. 12, 15: imaging cells;
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); and
managing, by a cell editing subsystem, a cell culture process performed on the cell culture over a period of time based on the time-series image data, wherein managing the cell culture process comprises (Madrid: page 3, 3rd para: “The imaging system is provided to image cells on the substrate. The computing system is provided to compute cell characteristics from one or more images. The computing system is used to direct a pulsed laser scanning system. The pulsed laser scanning system directs laser pulses to the substrate under targeted cells, where laser pulses are converted into mechanical energy via microbubbles. The microbubbles, depending on laser energy and pulse pattern, are used to destroy selected cells, remove selected cells, temporarily porate selected cells for the purpose of introducing biological cargos, or a combination thereof.”;
Fig. 1 (shown above): mainly 5104):
(a) performing selective removal of a least a portion of the cell culture to reduce a confluence or density of the cell culture (Madrid: page 19, 2nd-to-last para:
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); and
(b) performing selective removal of at least a portion of a cell colony of the plurality of cell colonies based at least in part on whether the cell colony will collide with another cell colony of the plurality of cell colonies (Madrid:
Page 19, last para – page 20, para 1: “The workflow in FIG 5 depicts how image-based laser-scanning could be used to keep various populations or colonies of cells separate within a single sample, well, or cell culture dish. At the time of imaging, multiple subpopulations of cells may be overlapping or growing in close proximity to each other 601; after laser-scanning, the subpopulations are separated 601 (FIG. 6).”
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).
Madrid does not teach closed.
Kelso teaches closed cell culture container, wherein the cell culture comprises a plurality of cell colonies (Kelso:
Para 9: “b) introducing a cell sample into the at least one compartment; c) transfecting the cell
sample with one or more transfection agents; d) selecting at least one clonal cell colony derived from the transfected cell sample; e) performing photoablation to destroy all clonal cell colonies except the at least one clonal cell colony selected in (d);”;
para 44: “a "compartment", "chamber", "reservoir", or "region" may be enclosed and sealed by a lid.”;
Figs. 1, 2, 3A-D, 9A-C, 5A-E, 8A-F;
Para 112: “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.”).
Thus, it would have been obvious for one of ordinary skill in the art, prior to filing, to implement the teachings of Kelso into Madrid since both Madrid and Kelso suggest a practical solution and field of endeavor of automated image guided cell culture processing based on imaging to select cells or colonies for laser-based removal in general and Kelso additionally provides teachings that can be incorporated into Madrid in that the cell culture container is closed as to “serve to prevent contamination of internal cartridge surfaces during storage and/or which prevent fluids from spilling when the cartridge is removed from an instrument” (Kelso: page 26, first para) and “to maintain sterile culture conditions and
prevent leakage” (Kelso: page 29, para 1). The teachings of Kelso can be incorporated into Madrid in that the cell culture container is closed. Furthermore, one of ordinary skill in the art could have combined the elements as claimed by known methods and, in combination, each component functions the same as it does separately. One of ordinary skill in the art would have recognized that the results of the combination would be predictable.
As per claim 2, Madrid in view of Kelso teaches the method of claim 1, wherein the cell culture process comprises at least one of expansion, reprogramming, differentiation, gene-editing, and cell purification/sorting (Madrid: See arguments and citations offered in rejecting claim 1 above;
Also see
page 20, para 1: “as a cell sorter to remove unwanted cells (for instance, cells that are
expressing an undesired phenotype) from the population”;
Figs. 7, 8, 15, 19).
As per claim 3, Madrid in view of Kelso teaches the method of claim 1, wherein managing the cell culture process further comprises performing one or more additional iterations of (a) and (b) over the period of time (Madrid: See arguments and citations offered in rejecting claim 1 above;
Also see
Figs. 5, 6, 12, 15;
Page 6, second to last para: “steps 1-3 are repeated until the cell type is achieved”;
Para 38, para 3: “the cycle is repeated and each time a minimal number of the genes is identified
as being responsible for directing cell differentiation of the desired cell type. The genes
identified in the first cycle, may also be identified in subsequent cycles. Cycles of the method
may be repeated to further enhance a phenotype of the cell type”;
Page 57, third to last para: “Iteration until the desired cellular phenotype is achieved”;
Page 57, second to last para: “repeated until the desired cellular type is identified using the disclosed systems and methods”||
Kelso: page 6, para 1, para 10: “the imaging is performed at a frequency of at least once per hour. In some embodiments, the selecting in ( d) is performed automatically based on automated image analysis of one or more images”;
Para 153: “repeated cycles”).
As per claim 6, Madrid in view of Kelso teaches the method of claim 3, wherein the one or more additional iterations are performed to either purify the cell culture into a single cell type or to increase monoclonality of the cell culture (Madrid: See arguments and citations offered in rejecting claim 1 above;
Page 19, last para: “elimination of cells not expressing the desired phenotype,”||
Kelso:
Para 9: “b) introducing a cell sample into the at least one compartment; c) transfecting the cell
sample with one or more transfection agents; d) selecting at least one clonal cell colony derived from the transfected cell sample; e) performing photoablation to destroy all clonal cell colonies except the at least one clonal cell colony selected in (d);”
Figs. 8A-F).
As per claim 7, Madrid in view of Kelso teaches the method of claim 1, wherein the cell culture comprises induced pluripotent stem cells (Madrid: See arguments and citations offered in rejecting claim 1 above;
Also see
Page 7, para 3: “induced pluripotent stem cells (iPS cells or iPSC), which are pluripotent stem cells generated from adult cells”;
Page 22, last para: iPSCs;
Page 23, paras 1-2: iPSCs;
Page 24, para 1: iPSCs;
Pages 29, 35, 50, 51, etc: iPSCs;
Figs. 15, 16, 20 ||
Kelso: paras 50, 64, 68, 73, 113, 201: iPSCs).
As per claim 8, Madrid in view of Kelso teaches the method of claim 1. Madrid does not teach the closed cell culture container comprises a closed liquid path providing fluid media to the cell culture.
Kelso teaches these limitations (Kelso: See arguments and citations offered in rejecting claim 1 above;
Paras 86-90: fluid;
Figs. 1-3;
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Thus, it would have been obvious for one of ordinary skill in the art, prior to filing, to implement the teachings of Kelso into Madrid since both Madrid and Kelso suggest a practical solution and field of endeavor of automated image guided cell culture processing based on imaging to select cells or colonies for laser-based removal in general and Kelso additionally provides teachings that can be incorporated into Madrid in that the container has a closed liquid path providing fluid media as to “provide efficient delivery of cells and other reagents” (Kelso: para 56). The teachings of Kelso can be incorporated into Madrid in that the container has a closed liquid path providing fluid media. Furthermore, one of ordinary skill in the art could have combined the elements as claimed by known methods and, in combination, each component functions the same as it does separately. One of ordinary skill in the art would have recognized that the results of the combination would be predictable.
As per claim 9, Madrid in view of Kelso teaches the method of claim 1, wherein cell culture remains in the same closed cell culture container while managing the cell culture process during the period of time (Madrid: See arguments and citations offered in rejecting claim 1 above; Page 27, first para (shown above) ||
Kelso: page 8: “cell transfection, cell selection, and cell expansion are all performed in the same compartment.”;
para 66: “a cell selection compartment may also function as a clonal cell expansion compartment”).
As per claim 10, Madrid in view of Kelso teaches the method of claim 1, wherein the closed cell culture container comprises a cell culture chamber having a first semi-transparent surface upon which the cell culture is adhered, the first semi-transparent surface comprising a laser-activated film (Madrid: See arguments and citations offered in rejecting claim 1 above;
Abstract: “The substrate is suitable for high-resolution cell imaging and is coated with a layer that partially absorbs laser pulses for the purpose of converting energy into micro bubble formation.”;
Page 13, para 1: “Therefore, when viewed in a direction moving away from the laser source and imaging side, the stacked layers of the substrate comprise an antireflection coating, a bulk substrate material (i.e., glass), a partially-absorbing layer (i.e., Ti), extracellular matrix, and cells.”;
Page 13, second to last para: “a coating layer of the substrate absorbs, or partially absorbs, laser
pulses to convert optical energy into microbubble formation. The method further comprises
destroying selected cells with the microbubble formation. The method further comprises
removing selected cells with the microbubble formation. The method further comprises porating
selected cells with the microbubble formation. In some embodiments, porating selected cells is a
temporary poration.”;
page 35, second to last para: “The cells are plated onto 384 well plates that are fitted with an optically clear substrate that has regularly spaced optical absorption/ bubble nucleation sites on the well-facing surface, for example patches of metallic absorber with a sufficiently rough top surface to promote microsecond bubble nucleation upon exposure to a short laser pulse.”;
Fig. 2 (shown above): mainly 202, 203).
As per claim 11, Madrid in view of Kelso teaches the method of claim 10, wherein the laser-activated film transmits incident light in a first range of wavelengths for imaging functions and absorbs incident light in a second range of wavelengths for cell removal functions (Madrid: See arguments and citations offered in rejecting claim 1 above;
Page 13, para 2: “the pulsed laser scanner transmits laser pulses at a wavelength of greater than about 500 nm. In preferred embodiments, the pulsed laser scanner transmits laser pulses at a wavelength of about 532 nm”;
Page 4, second to last para: “The absorbing layer absorbs transmission at one or more imaging wavelengths of preferably greater than about 25%, about 50%, or about 75%. Wavelengths absorbed are in the range of about 400 nm to about 700 nm. In some embodiments, absorption is at a pulsed laser wavelength of greater than about 5%, about 10%, about 15%, about 25%, or about 50%. In an embodiment, the design features over a majority of the absorbing layer surface are not larger than about 0.25 wavelength, about 0.5 wavelength, about 1.0 wavelength, or about 2.0 wavelength of the imaging light.”;
Page 5, second para: “the substrate may go through transmission at imaging wavelengths”).
As per claim 12, Madrid in view of Kelso teaches the method of claim 1, wherein managing the cell culture process further comprises fragmenting a first cell colony of the plurality of cell colonies into a plurality of sub-colonies (Madrid: See arguments and citations offered in rejecting claim 1 above;
Page 20, para 1: “the subpopulations are separated 601 (FIG. 6)”;
Fig. 6 (shown above) ||
Kelso: See arguments and citations offered in rejecting claim 1 above).
As per claim(s) 13-15 and 18-24, arguments made in rejecting claim(s) 1-3 and 6-12 are analogous, respectively.
Claim(s) 4, 5, 16, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Madrid in view of Kelso as applied to claims 3 and 15 above, and further in view of Official Notice.
As per claim 4, Madrid in view of Kelso teaches the method of claim 3. Madrid in view of Kelso does not teach the period of time is at least ten days. Examiner provides Official Notice that these limitations were well known prior to filing.
One of ordinary skill in the art, prior to filing, would have recognized the advantage of sustained hands-off management over a long run. The teachings of the prior art could have been incorporated into Madrid in view of Kelso in that the period of time is at least ten days.
As per claim 5, Madrid in view of Kelso and Official Notice teaches the method of claim 4. Madrid in view of Kelso does not teach the period of time is at least thirty days. Examiner provides Official Notice that these limitations were well known prior to filing.
One of ordinary skill in the art, prior to filing, would have recognized the advantage of sustained hands-off management over a long run. The teachings of the prior art could have been incorporated into Madrid in view of Kelso in that the period of time is at least thirty days.
As per claim(s) 16 and 17, arguments made in rejecting claim(s) 4 and 5 are analogous, respectively.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Atiba Fitzpatrick whose telephone number is (571) 270-5255. The examiner can normally be reached on M-F 10:00am-6pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Bee can be reached on (571) 270-5183. The fax phone number for Atiba Fitzpatrick is (571) 270-6255.
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Atiba Fitzpatrick
/ATIBA O FITZPATRICK/
Primary Examiner, Art Unit 2677
