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 .
Information Disclosure Statement
The information disclosure statement filed on 03/18/25 fails to comply with the provisions of 37 CFR 1.98(a)(4) because it lacks the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 44 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
The claim(s) recite(s) an additional step of “diagnosing a condition of the subject based on the cross-sectional image of the target cell”. This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers an abstract idea in the form of a mental process. The claim recites making diagnostic determination base on the visualized data. Making decision based on provided data, under broadest reasonable interpretation, is a mental process that can be performed in the human mind. Nothing in the claim precludes the user from mentally/manually analyzing the data and deciding what would be constituted as “suggesting” the subject is experiencing a condition. If a claim limitation, under its broadest reasonable interpretation, covers a mental process, then it falls within the mental process grouping. Accordingly, the claim recites an abstract idea (Step 2A, Prong 1).
This judicial exception is not integrated into a practical application. In particular, the claim recites suggesting that the subject is experience a condition based on the visualized data, which constitutes a mental process under broadest reasonable interpretation. After the diagnostic is completed, nothing is done with the information. Therefore, there is no integration of the diagnostic step much less a practical one since after the information is obtained. Accordingly, this additional element does not integrate the mental process into a practical application because it does not impose any meaningful limits on practicing the abstract idea (Step 2A, Prong 2).
The claim does not include additional elements that are sufficient to amount to significant more than the judicial exception. With respect to integration of the abstract idea into a practical application, the rest of the limitation, contacting sample with probes/tags/labels (See step (a) of claim 30) and generating images (See step (b) of claim 30) of the sample appear to be routine and conventional data gathering. Routine data gathering cannot provide an inventive concept (Step 2B). Hence, the claim is not patent eligible.
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) 30-34 and 44-49 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tomer (US 20190056581 A1).
Regarding claim 30, Tomer discloses a method (a method…for imaging a biological sample; abstract), comprising:
(a) contacting a target cell with a heterologous detection moiety (binding member) (In some cases, the biological sample contains one or more cells that are associated with a detectable label, e.g., a fluorescent label, colorimetric label, etc. para. [0134]), wherein the heterologous detection moiety exhibits specific binding to a heterologous nucleic acid sequence in the target cell (In some cases, a binding member, e.g., an antibody, that specifically binds to a cellular component, e.g., a cell surface marker on the cells, may be conjugated with a detectable label, e.g., a fluorescent dye or protein, and the labeled binding member may be used to label the cells indirectly. In some cases, the binding member is a nucleic acid that includes a sequence that hybridizes with a target sequence in cells of the biological sample, and the nucleic acid may be conjugated to a detectable label. Para. [0134]); and
(b) directing a light sheet at a cross-section of the target cell to obtain a cross-sectional image of the target cell (Provided herein is a method for imaging a biological sample, the method including a) scanning a biological sample using one or more light sheets; para. [0005]), wherein the light sheet comprises a wavelength sufficient to detect the heterologous detection moiety (A fluorescent label may be a fluorescent dye or a fluorescent protein that enables the cells to emit fluorescence in response to an appropriate light sheet illumination (e.g., light sheet illumination having the appropriate wavelength and intensity of illumination). Para. [0134]), wherein the heterologous detection moiety is complexed with the heterologous nucleic acid sequence in the target cell (para. [0051] and [0134]).
Regarding claim 31, Tomer discloses the claimed invention as discussed above in claim 30. Tomer discloses the method further comprises directing the light sheet at a plurality of cross-sections of the target cell and thereby obtaining contiguous cross-sectional images of the target cell (para. [0117]).
Regarding claim 32-33, Tomer discloses the claimed invention as discussed above in claim 31. Tomer discloses the method comprises compiling the contiguous cross-sectional images to generate a composite image of the target cell, wherein the composite image is a three-dimensional (3D) image of the target cell (Each pair of adjacent slices of the z-axial slices of the biological sample imaged by the present method…to generate a three-dimensional image of the sample. Para. [0117]; also in para. [0118]).
Regarding claim 34, Tomer discloses the claimed invention as discussed above in claim 30. Tomer discloses the heterologous detection moiety is conjugated to a tag (detectable label) that can be detected upon exposure of electromagnetic radiation (In some cases, the biological sample contains one or more cells that are associated with a detectable label, e.g., a fluorescent label, colorimetric label, etc. A fluorescent label may be a fluorescent dye or a fluorescent protein that enables the cells to emit fluorescence in response to an appropriate light sheet illumination. Para. [0134]).
Regarding claim 44, Tomer discloses the claimed invention as discussed above in claim 30. Tomer discloses the target cell is derived from a subject (An implementation of the method of diagnosing the tissue sample may include obtaining a tissue sample from an individual… para. [0128]), and wherein the method further comprises diagnosing a condition of the subject (analyzing images of the sample to diagnose a condition of the individual (analyzing, qualitatively or quantitatively, one or more images of the image stack for one or more features diagnostic of pathology, thereby diagnosing the tissue sample. Para. [0128]).
Regarding claim 45, Tomer discloses the claimed invention as discussed above in claim 30. Tomer discloses the method further comprises determining a presence of the heterologous nucleic acid sequence in the target cell (In some cases, the binding member is a nucleic acid that includes a sequence that hybridizes with a target sequence in cells of the biological sample, and the nucleic acid may be conjugated to a detectable label. Para. [0134]) based on the cross-sectional image of the target cell (By capturing the emitted light pattern from different slices, an image of the sample corresponding to the z-axial position of the light sheet that illuminated that slice can be generated. Para. [0105]; the cells of the biological sample…include a fluorescent moiety… that enables the cells to emit fluorescence in response to an appropriate light sheet illumination. Para. [0134]).
Regarding claim 46, Tomer discloses the claimed invention as discussed above in claim 30. Tomer discloses the method further comprises directing an additional light sheet at an additional cross-section of the target cell to obtain an additional cross-sectional image of the target cell (In some embodiments, the biological sample is illuminated by the two light sheets from opposite sides of the biological sample; para. [0008]), wherein the additional light sheet comprises an additional wavelength sufficient to detect a marker of the target cell (A fluorescent label may be a fluorescent dye or a fluorescent protein that enables the cells to emit fluorescence in response to an appropriate light sheet illumination (e.g., light sheet illumination having the appropriate wavelength and intensity of illumination; para. [0134]; the claim language does not specify that the additional light sheet have a wavelength different than that of the first).
Regarding claim 47, Tomer discloses the claimed invention as discussed above in claim 46. Tomer discloses the method further comprises compiling the cross-sectional image and the additional cross-sectional image into a composite image (In some cases, the different fields of view may be positioned so as to generate images that are tiled across the biological sample x-y plane to cover a contiguous surface of the sample larger than the field of view of the microscope. Para. [0123]).
Regarding claim 48, Tomer discloses the claimed invention as discussed above in claim 30. Tomer discloses the target cell is a human cell (para. [0054]).
Regarding claim 49, Tomer discloses the claimed invention as discussed above in claim 30. Tomer discloses the target cell is an immune cell (In some cases, the pathology is infiltration of immune cells. Para. [0129]).
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.
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.
Claim(s) 35-42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tomer in view of Wang (A Novel in Situ RNA Analysis Platform for Formalin-Fixed, Paraffin-Embedded Tissues, 2012).
Regarding claims 35-36, Tomer discloses the claimed invention as discussed above in claim 30. Tomer discloses the heterologous detection moiety comprises a polynucleotide (nucleic acid sequence) (In some cases, the binding member is a nucleic acid that includes a sequence that hybridizes with a target sequence in cells of the biological sample; para. [0134]). Tomer does not disclose explicitly the polynucleotide comprises from about 15 to about 25 nucleobases.
In an analogous art, Wang discloses a detection moiety comprising a polynucleotide of about 18-25 nucleobases (each target probe contains an 18-25 base region complementary to the target RNA; page 23, 1st column, 4th paragraph). It would have been obvious to a person of ordinary skill in the art before the effective filing date to have modified the method as disclosed by Tomer to incorporate a polynucleotide of about 18-25 nucleobases, as taught by Wang, as Tomer discloses a detection moiety comprising a polynucleotide and Wang discloses a detection moiety comprising a polynucleotide a polynucleotide of about 18-25 nucleobases, and this combination would have provided the capability of using the amplified signal system disclosed by Wang with the light sheet detection system disclosed by Tomer, thereby increasing signal strength and sensitivity (We sought to improve the signal-to-noise ratio of RNA ISH by amplifying target-specific signals but not background noise from nonspecific hybridization. We used a novel target probe design strategy (a double-Z design) (Figure 1). Page 23, 1st column, 4th paragraph).
Regarding claims 37-38, Tomer discloses the claimed invention as discussed above in claim 30. Tomer does not disclose wherein the heterologous detection moiety comprises a plurality of heterologous detection moieties, wherein an individual heterologous detection moiety of the plurality of heterologous detection moieties exhibits specific binding to a target heterologous nucleic acid sequence that is different from other target heterologous nucleic acid sequences of other heterologous detection moieties of the plurality of heterologous detection moieties, wherein the plurality of heterologous detection moieties comprises at least about 5 different heterologous detection moieties.
Wang discloses a plurality of heterologous detection moieties (target probes) (multiple RNA species may be measured simultaneously with target probes for different genes; page 23, 2nd column, 4th paragraph), wherein an individual heterologous detection moiety of the plurality of heterologous detection moieties exhibits specific binding to a target heterologous nucleic acid sequence that is different from other target heterologous nucleic acid sequences of other heterologous detection moieties of the plurality of heterologous detection moieties (multiple RNA species may be measured simultaneously with target probes for different genes; page 23, 2nd column, 4th paragraph), wherein the plurality of heterologous detection moieties comprises at least about 5 different heterologous detection moieties (We chose 10 to 20 pairs, for optimal signals and for added robustness against potentially variable target accessibility and partial RNA degradation; page 24, 1st column, 1st paragraph).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to have modified the method as disclosed by Tomer to incorporate a plurality of heterologous detection moieties, specifically at least 5 or more, with specific binding to different target sequences, as taught by Wang, as Tomer discloses heterologous detection moieties, Wang discloses a plurality of different heterologous detection moieties with specificity to different sequences, and this combination would have provided the capability of multiplex detection of multiple target sequences (…multiple signal amplification systems with different label probes can be used to detect each RNA species, allowing for multiplex detection of multiple target RNAs. page 23, 2nd column, 4th paragraph).
Regarding claim 39, Tomer discloses the claimed invention as discussed above in claim 30. Tomer does not disclose wherein the heterologous detection moiety is an RNA-fluorescence in situ hybridization, FISH, probe.
In an analogous art, Wang discloses the heterologous detection moiety is an RNA-fluorescence in situ hybridization, FISH, probe (Here, we describe RNAscope, a novel RNA ISH technology with a unique probe design strategy...RNAscope is compatible with routine formalin-fixed, paraffin-embedded tissue specimens and can use…fluorescent dyes for multiplex analysis.; abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to have modified the method as disclosed by Tomer to incorporate an RNA-fluorescence in situ hybridization, FISH, probe, as taught by Wang, as Tomer discloses heterologous detection moieties, Wang discloses wherein the heterologous detection moiety is an RNA-fluorescence in situ hybridization, FISH, probe, and this combination would have provided the capability of detecting RNA in situ using the sensitive detection methods provided by Tomer (Wang, allows simultaneous signal amplification and background suppression to achieve single-molecule visualization while preserving tissue morphology, Abstract).
Regarding claims 40-41, Tomer discloses the claimed invention as discussed above in claim 30. Tomer does not disclose the heterologous nucleic acid sequence is derived from a genome of a virus, wherein the heterologous nucleic acid sequence is native to the virus and is not artificially introduced into a genome of the virus or the heterologous nucleic acid sequence is a mRNA sequence derived from a viral nucleic acid sequence.
In an analogous art, Wang discloses the heterologous nucleic acid sequence is derived from a viral nucleic acid sequence (a probe set targeting HCV RNA was used to detect a viral transcript in cells; page 25, 1st column, 4th paragraph), wherein the heterologous nucleic acid sequence is native to the virus and is not artificially introduced into a genome of the virus (a viral transcript in HuH-7 cells stably infected with HCV, page 25, 1st column, 4th paragraph). It would have been obvious to a person of ordinary skill in the art before the effective filing date to have modified the method as disclosed by Tomer to incorporate a viral-derived heterologous nucleic acid sequence, as taught by Wang, as Tomer discloses detection of heterologous nucleic acid sequences in cells, Wang discloses detection of viral nucleic acid sequences in cells, and this combination would have provided the capability of detecting viral RNA in situ using the sensitive detection methods provided by Tomer (Wang, Positive punctate staining was detected in HCV-infected cells, but not in uninfected control cells… Each target probe set gave positive staining only in the cell line known to harbor the corresponding HPV genotype, page 25, 1st column, 4th paragraph).
Regarding claim 42, Tomer discloses the claimed invention as discussed above in claim 30. Tomer does not disclose the heterologous nucleic acid sequence encodes at least a portion of a viral protein.
In an analogous art, Wang discloses the heterologous nucleic acid sequence encodes at least a portion of a viral protein (a probe set targeting HCV RNA was used to detect a viral transcript in HuH-7 cells stably infected with HCV; page 25, 1st column, 4th paragraph). It would have been obvious to a person of ordinary skill in the art before the effective filing date to have modified the method as disclosed by Tomer to incorporate the heterologous nucleic acid sequence comprising a viral nucleic acid sequence, as taught by Wang, as Tomer discloses detection of heterologous nucleic acid sequences in cells, Wang discloses detection of viral nucleic acid sequences in cells, and this combination would have provided the capability of detecting viral protein-encoding RNA in situ using the sensitive detection methods provided by Tomer (Wang, Positive punctate staining was detected in HCV-infected cells, but not in uninfected control cells… Each target probe set gave positive staining only in the cell line known to harbor the corresponding HPV genotype, page 25, 1st column, 4th paragraph).
Claim(s) 43 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tomer in view of Wang as applied to claim 42 above, and further in view of Haddad (Identification of Novel Functions for Hepatitis C Virus Envelope Glycoprotein E1 in Virus Entry and Assembly, 2017).
Regarding claim 43, Tomer discloses the claimed invention as discussed above in claim 42. Wang (after incorporation with Tomer) discloses the viral protein is derived from HCV but does not explicitly utilizing a viral surface protein.
In an analogous art, Haddad discloses conducting a in situ hybridization on surface viral protein E1 of HCV (Finally, we also analyzed whether the D263A mutation affects the colocalization of core protein or E1 with the viral RNA. For this, we analyzed the localization of HCV RNA by fluorescence in situ hybridization (FISH). Page 11, paragraph 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to have modified the method as disclosed by Tomer in view of Wang to incorporate the heterologous nucleic acid sequence comprising a surface viral protein, as taught by Haddad, as Tomer discloses detection of heterologous nucleic acid sequences in cells, Wang discloses detection of HCV protein sequences in cells, Haddad discloses detection of both HCV RNA and surface protein such as E1, and this combination would have provided the capability of detecting E1 viral surface protein in situ using the sensitive detection methods provided by Tomer (Haddad, Finally, a change in subcellular colocalization between HCV RNA and E1 was observed for the D263A mutant. This unique observation highlights for the first time cross talk between HCV glycoprotein E1 and the genomic RNA during HCV morphogenesis. Abstract).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICKEY HUANG whose telephone number is (571)272-7690. The examiner can normally be reached M-F 9:30-5:30 PM ET.
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/M.H./Examiner, Art Unit 1758
/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758