5:45DETAILED 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 .
Specification
The use of the terms “Invitrogen”, “GE Healthcare”, “Alexa Fluor”, “Astrazon”, “GeneBLAzer”, “MitoTracker”, “Sytox”, “Sigma-Aldritch”, “Texas Red” etc., which are trade names or a marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears 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.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
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 6 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 6 is unclear over the limitation: “wherein each of the different focal planes is focused at no more than…”. The language makes it unclear if the focal planes are doing the focusing.
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)(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.
Claims 1 and 7 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Frost (US PG PUB 20020094116, published 07/18/2002).
Regarding claim 1, Frost teaches a method comprising exposing a sample to a plurality of nucleic acid probes which bind to target nucleic acids (e.g., Frost abstract, para 0070, para 0024), and detecting the binding of the probes by capturing images using at least four detectors which can focus on different focal planes (e.g., Frost para 0122, 0011, 0016, FIG 16a), and determining abundance (e.g., Frost para 0192) or spatial distribution (e.g., Frost FIG 17) based on the binding determined in the images.
Regarding claim 7, Frost teaches a method comprising passing light from the sample through a plurality of beam splitters to the at least 4 detectors (e.g., Frost FIG 16c, para 0053, 0102).
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.
Claims 15, 21, 22, 25-28, 32-34, 36, 38 and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Frost in view of Cai (WO 2018/026873 published 02/08/2018, Foreign patent document on sheet 8 of IDS dated 04/24/2024).
Frost anticipates a method detecting a target via binding of nucleic acid probes and imaging at multiple focal points upon which the instantly rejected claims 1 and 7 depend, as described above. Frost does not teach multiple probes, multi-color fluorescence imaging, error correction, codewords/barcodes, detections within fixed cells and specific sizes of nucleic acid probes, whoever these were known in the art and were taught by Cai.
Regarding claim 15, Cai teaches a method of nucleic acid detection comprising binding bridge oligonucleotides to primary probes, which are specific to target nucleic acid sequences (e.g., Cai FIG 26), reading on the limitation “ exposing the nucleic acid probes to primary amplifier nucleic acids able to bind to the nucleic acid probes, wherein a maximum number of primary amplifier nucleic acids is able to bind to a nucleic acid probe” of the instantly rejected claim 15. Cai further teaches binding the tertiary readout probes to the bridge oligonucleotides (e.g., Cai FIG 26) reading on the limitation “primary amplifier nucleic acids to secondary amplifier nucleic acids able to bind to the primary amplifier nucleic acids, wherein a maximum number of secondary amplifier nucleic acids is able to bind to the primary amplifier nucleic acids” of the instantly rejected claim 15.
Regarding claim 21, Cai teaches a method wherein the secondary amplifier nucleic acids comprise a fluorescent signaling entity (e.g., Cai para 0210).
Regarding claim 22, Cai teaches a method comprising creating codewords by binding of the nucleic acid probes within the sample; and for at least some of the codewords, matching the codeword to a valid codeword optionally wherein, if no match is found, applying error correction to the codeword to form a valid codeword (e.g., Cai para 409).
Regarding claim 25, Cai teaches a method wherein the plurality of nucleic acid probes comprises a combinatorial combination of nucleic acid probes with different sequences (e.g., Cai para 409).
Regarding claim 26, Cai teaches a method wherein the plurality of nucleic acid probes have an average length of between 10 and 300 nucleotides (e.g., Cai para 0139).
Regarding claim 27, Cai teaches a method wherein at least some of the plurality of nucleic acid probes comprises a target sequence and one or more read sequences (e.g., Cai para 0168).
Regarding claim 28, Cai teaches a method wherein the target sequence of the plurality of nucleic acid probes has an average length of between 10 and 200 nucleotides (e.g., Cai para 0139).
Regarding claim 32, Cai teaches a method comprising determining binding of the nucleic acid probes using fluorescence imaging (e.g., para 0072, 00155).
Regarding claim 33, Cai teaches a method comprising determining binding of the nucleic acid probes using multi-color fluorescence imaging (e.g., Cai 0409).
Regarding claim 34, Cai teaches a method comprising determining binding of the nucleic acid probes using a super-resolution fluorescence imaging technique (e.g., Cai para 00274).
Regarding claim 36, Cai teaches a method wherein the sample comprises a cell (e.g., Cai para 0406, 0084).
Regarding claim 38, Cai teaches a method wherein the cell is fixed (e.g., Cai para 0406).
Regarding claim 39, Cai teaches a method comprising exposing a sample to a plurality of nucleic acid probes; for each of the nucleic acid probes, exposing the nucleic acid probes to amplifier nucleic acids able to bind thereto, wherein a maximum finite number of amplifier nucleic acids is able to directly or indirectly bind to each of the nucleic acid probes; and for each of the nucleic acid probes, simultaneously capturing images of the sample using at least 4 cameras focused on different focal planes within the sample (e.g., Cai FIG 26; Frost FIG 16a, para 0122).
It would have been prima facie obvious before the effective filing date of the claimed invention for a person having ordinary skill in the art to have used the method of Cai of binding multiple probes associated with different fluorophores probes bound to target nucleic acids within a fixed cell and using error correction on images taken, with the method of detecting a target via binding of nucleic acid probes and imaging at multiple focal points of Frost. The person having ordinary skill would have been motivated to combine these methods by the teachings of Cai that their method can be widely used to answer a wide range of fundamental questions in biology and medicine (e.g., Cai para 00446), allows robust multiplexed nucleic acid detection in tissues (e.g., Cai para 00443) and their error correction scheme is efficient in practical implementation (e.g., Cai para 00409). Thus the addition of the method of Cai to the method of detecting a target via binding of nucleic acid probes and imaging at multiple focal points of Frost would have been a simple combination of prior art elements according to known methods to yield predictable results.
Claims 6, 8, 14 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Frost in view of Cai, in further view of Zhuang (US PG PUB 2011/0002530, published 01/06/2011, US Patent document on sheet 4 of IDS dated 04/24/2024).
Frost anticipates a method detecting a target via binding of nucleic acid probes and imaging at multiple focal points upon which the instantly rejected claims 1 and 7 depend, as described above. Frost in view of Cai renders obvious claims 15, 21, 22, 25-28, 32-34, 36, 38 and 39 of the instantly rejected claim as described above. Frost in view of Cai does not teach specific resolutions for imaging, the use of beam splitters and cameras nor stochastic optical reconstruction microscopy, but these were known in the art and were taught by Zhuang.
Regarding claim 6, Zhuang teaches a method wherein each of the different focal planes is focused at no more than 1000 nm from a neighboring focal plane (e.g., Zhuang para 0018).
Regarding claim 8, Zhuang teaches a method wherein the detectors are cameras (e.g., Zhuang para 0040).
Regarding claim 14, Zhuang teaches a method comprising determining z positions of the nucleic acid probes in the sample at a resolution of at least 300 nm (e.g., Zhuang para 0028).
Regarding claim 35, Zhuang teaches a method comprising determining binding of the nucleic acid probes using stochastic optical reconstruction microscopy (STORM) (e.g., Zhuang para 0076, 0082).
It would have been prima facie obvious before the effective filing date of the claimed invention for a person having ordinary skill in the art to have used the method of Zhuang of specific resolutions for imaging, the inclusion of beam splitters and cameras and stochastic optical reconstruction microscopy in their detection with the method of detection of Frost in view of Cai of binding multiple probes associated with different fluorophores probes bound to target nucleic acids within a fixed cell, taking images at multiple focal planes and using error correction on images taken. The person having ordinary skill would have been motivated to combine these methods by the teachings of Zhuang that their method may significantly enhance the ability to visualize molecular organization and interaction networks in cells (e.g., Zhuang para 0063).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Frost in view of view of Babcock (2018, published 01/20/2018, NPL on sheet 11 of IDS dated 04/24/2024).
Frost anticipates a method detecting a target via binding of nucleic acid probes and imaging at multiple focal points upon which the instantly rejected claims 1 and 7 depend, as described above. Frost does not teach the use of more than five detectors, but this was known in the art and was taught by Babcock.
Regarding claim 3, Babcock teaches the use of multiple detectors in their method of fluorescence imaging (e.g., Babcock Figure 1).
Although Babcock does not teach the use of at least 8, at least 16 or at least 32 detectors, they do suggest their method is scalable to 4, 8 or even more cameras/detectors (e.g., Babcock page 6, para 2). It would have been prima facie obvious to someone having ordinary skill in the art before the effective filing date of the claimed invention to optimize their detector set-up based on the methods of Babcock. Where the prior art teaches the use of different detectors, and the upward scalability of the set-up, a person of ordinary skill has good reason to pursue the known options within their technical grasp for optimization of fluorescence detection when they are targeting multiple focal points. If this leads to success, it is likely the product not of innovation, but of ordinary skill and common sense to provide routine optimization.
Conclusion
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/G.Y./Examiner, Art Unit 1683 /CYNTHIA B WILDER/Supervisory Patent Examiner, Art Unit 1683
Prosecution Insights