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 1-35 are pending and examined on their merits below. Please note that two sets of claims were filed on Aug. 30, 2023 and that these appear to be duplicates of one another.
Priority
The application claims priority to provisional applications 63/170419, filed April 2, 2021 and 63/173876, filed April 12, 2021; as such the earliest possible priority date is April 2, 2021.
Information Disclosure Statement
The information disclosure statement filed Aug. 30, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the examiner.
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) 1-7, 10, 12, 13, 19, 20, 22, 23 and 27-32 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee et al. (U.S. Patent App. No. (U.S. Patent App. No. 2019/0316995 A1, cited in IDS filed on Aug. 30, 2023).
With respect to independent claim 1, Lee et al. teach a blood sample staining method including preparing a blood sample, contacting the blood sample with a first hydrogel stamp to stain the blood sample with a first staining dye (“contact-type staining patches” which contains “a gel receptor”, the gel receptor being a hydrogel), removing the first hydrogel stamp, placing the blood sample in contact with a second hydrogel stamp to stain the blood sample with a second staining dye, removing the second hydrogel stamp, placing the blood in contact with a third hydrogel stamp that includes a buffer substance that absorbs excessive unbound or weakly bound dye from the blood sample (“contact type staining supplementary patch” which absorbs some of the extra stain) and removing the third hydrogel stamp. (Abstract, paras. [0011], [0028], [0044], [0045], [0117], [0139], [0251], [0253], Figs. 13, 14.) Lee et al. teach that this system can allow for no intermediate washing step after staining with the first or second staining dye, as the contact-type supplementary patch, which contains a buffer eliminates the need for this, making the process faster and easier. (paras. [0079, [0176], [0184]-[0186], [0201], [0216], [0217], [0403]).
With respect to dependent claim 2, Lee et al. teach that the blood sample can be prepared through smearing. (Fig. 23, paras. [0054], [0055], [0174]).
With respect to dependent claim 3, Lee et al. teach that a fixing patch with a fixing agent such as ethanol or methanol can be used to fix the blood specimen on the slide. (para. [0229]).
With respect to dependent claim 4, Lee et al. teach that a first contact-type staining patch can have eosin and a second one can have methylene blue. (para. [0139]).
With respect to dependent claim 5, Lee et al. teach that a methylene blue patch, then eosin patch can be applied prior to application of a buffering patch. (Fig. 13, para. [0044], [0045]).
With respect to dependent claims 6 and 7, Lee et al. teach the hydrogel can be agarose. (paras. [0081]-[0083]).
With respect to dependent claims 10 and 12, Lee et al. teach the contact-type staining patch can be used to detect malaria, which inherently teaches the blood sample would contain red blood cells, as malaria detection would be through examination of red blood cells. (para. [0120]).
With respect to claims 13, 19 and 20, Lee et al. teach a methylene blue patch (first hydrogel) is brought into contact with the blood for 30 seconds, an eosin patch is brought into contact with the blood for approximately one minute (approximately one minute encompassing “less than one minute”), and the buffering patch (3rd patch) is brough into contact with the blood for approximately 3 minutes (“about 180 seconds”). (para. [0277]).
With respect to dependent claims 22 and 23, Lee et al. teach the buffering solution has a pH range of 6.8 to 7.4, (para. [0087]), which encompasses “about 6.8”.
With respect to dependent claims 27-29, Lee et al. teach the stain may include hematoxylin, Gram staining solution, or Papanicoulaou. (paras. [0120], [0134]).
With respect to dependent claims 30-32, Lee et al. teach that agarose can be present at a concentration of 1-4%, and more specifically 1.5-2.5%. (paras. [0092], [[0174], which would encompass the claimed ranges, including “about 2%”.
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.
Claim(s) 14-18, 21 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (U.S. Patent App. No. (U.S. Patent App. No. 2019/0316995 A1, cited in IDS filed on Aug. 30, 2023), as applied to claims 1-7, 10, 12, 13, 19, 20, 22, 23 and 27-32 above.
With respect to dependent claims 14-18 and 21, Lee et al. teach that one of the benefits of the staining process is that is can be performed much faster than convention blood smear staining. (para. [0201]).
With respect to claim 14, Lee et al. teach that the entire process takes 30 seconds for the first patch, approximately one minute for the second patch, and three minutes for the buffering patch, which would mean the process takes approximately 4 minutes and 30 seconds. It would have been prima facie obvious to have shortened the process from approximately 4 minutes and seconds to less than 4 minutes because this is a result effective variable.
With respect to claims 16-18 (which all include the configuration of claim 4 – the first stain is eosin and second stain is methylene blue), Lee et al. teach Lee et al. teach a methylene blue patch (first hydrogel) is brought into contact with the blood for 30 seconds, an eosin patch is brought into contact with the blood for approximately one minute. (para. [0277]). Lee et al. also teaches the first patch can be eosin and the second patch can be ethylene blue (para. [0139]), but does not teach a time scheme for this configuration. It would have been obvious to change the order of these dyes and to have tried the claimed time frames for staining, as this is a result effective variable.
With respect to claim 21, Lee et al. teaches that malaria can be detected, but does not teach a timeframe for doing so. However, this is also seen as a result effective variable, as Lee et al. explicitly teach the advantage of faster performance using the improved staining method and teach staining for malaria. It, therefore, would have been prima facie obvious to have tried the claimed parameters when staining for malaria.
With respect to claim 26, Lee et al. teach that the stain in the gel receptor is well-preserved, such that it can be reused and eliminate the wasting of stain. (paras. [0008], [0181], [0399]. Therefore, with Lee et al’s recognition that preservation of the stain and re-use are important cost and environmental factors, it would have been obvious to optimize the amount of reagent used for the first, second and third contact patches and to have arrived at the claimed about 1 mL amount, as doing so would offer a reliable process while using the least amount of reagent possible to lower expense and environmental damage.
It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). Since the prior art teaches that the process is much shorter than traditional staining methods and that the staining process can be performed in as little as 30 seconds, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the biotech art, which would include the claimed times.
Claim(s) 8, 9 and 33-35 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Lee et al. (U.S. Patent App. No. (U.S. Patent App. No. 2019/0316995 A1, cited in IDS filed on Aug. 30, 2023), as applied to claims 1-7, 10, 12, 13, 19, 20, 22, 23 and 27-32 above, and further in view of Armisen (Hydrobiologia, 1991).
Lee et al. does not teach that the agarose is uncharged, that it contains nm-scale channels or its specific mechanical hardness.
Specifically with respect to claims 33-35, Lee et al. teach that the hardness of the material used in the hydrogel will influence the amount of pressure required when using the contact-type staining patch and that the amount of stain necessary is dependent upon the hardness of the hydrogel. (paras. [0173], [0175]).
Armisen teaches that the highest quality agarose is uncharged, as this results in the greatest gelling ability (pg. 159, 1st full para.) and teaches a method of preparing agarose that is uncharged (EEO of 0). (pg. 163, 2nd col, 1st full para.).
It would have been obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the blood sample staining method taught by Lee et al. to incorporate using uncharged agarose with nm-scale channels and adjusting the mechanical hardness to the claimed parameters because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Making these modification would have led to predictable results with a reasonable expectation of success because these are, as taught by Lee et al. and Armisen, result effective variables when working with agarose.
It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). Since the prior art teaches the general aspects of the claimed parameters and reasons for optimization, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the biotech art, which would include the claimed times.
Claim(s) 11 and 24 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Lee et al. (U.S. Patent App. No. (U.S. Patent App. No. 2019/0316995 A1, cited in IDS filed on Aug. 30, 2023), as applied to claims 1-7, 10, 12, 13, 19, 20, 22, 23 and 27-32 above, and further in view of Lako & Rodig (Protocols.io, 2019).
Lee et al. teaches that blood smear examination may be used to test for infections, diseases, or abnormalities in blood cell morphology, including cancer. (para. [0003]).
With respect to claim 11, Lee et al. does not explicitly teach that the blood sample has white blood cells or, more specifically, neutrophils, lymphocytes, monocytes, eosinophils, or basophils.
With respect to claim 24, Lee et al. does not teach the blood sample includes FFPE sections.
Lako & Rodig teach a preparation protocol for hematoxylin and eosin (H&E) staining of FFPE tissue that allows distinguishing of tumor histology, morphology and visualization of tumor infiltrating lymphocytes. (pg. 1).
It would have been obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the blood sample staining method taught by Lee et al. to incorporate using a blood sample that includes FFPE sections having lymphocytes within it because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Making this modification would have led to predictable results with a reasonable expectation of success because Lako and Rodig teach an established protocol for making FFPE that enables H&E staining for visualization of tumor infiltrating lymphocytes and Lee et al. teach that blood smear examination is useful for detection of abnormalities, such as cancer. Therefore, these teachings could have been brought together by one of ordinary skill in the art to enable H&E staining in the method taught by Lee et al. after creating the blood sample including the FFPE tissue having lymphocytes (as taught by Lako & Rodig) to detect tumor infiltrating lymphocytes in a blood sample.
Claim(s) 25 is rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (U.S. Patent App. No. (U.S. Patent App. No. 2019/0316995 A1, cited in IDS filed on Aug. 30, 2023), and Lako & Rodig (Protocols.io, 2019), as applied to claims 11 and 24 above, and further in view of Hendry et al. (Adv Ant Pathol, 2017).
The combined teachings of Lee et al. and Lako & Rodig do not teach a particular type of tissue that is examined for tumor infiltrating lymphocytes.
Hendry et al. teach a standardized methodology for scoring tumor-infiltrating lymphocytes in solid tumors, including breast tissue, that can be applied in low-income countries that would include a biomarker based on a plan H&E stained section which is affordable and accessible. (Abstract, pg. 239, “Proposal for a Standardized Methodology for Scoring Tumor-Infiltrating Lymphocytes in Solid Tumors, in Both Primary and Metastatic Settings”, 1st para.)
It would have been obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the blood sample staining method taught by Lee et al. as modified by Lao & Rodig to incorporate including breast cells in the FFPE sections because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Making this modification would have led to predictable results with a reasonable expectation of success because Hendry et al. teach that following this method for scoring tumor-infiltrating lymphocytes in H&E stained slides increases therapeutic value and can be practiced in low-income countries (entire doc) and Lee et al. teach that their blood sample staining technique has the advantage of being low-cost, especially when being reused. (entire doc, see esp. para. [0181]).
Conclusion
No claims are allowed.
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/TERESA E KNIGHT/Primary Examiner, Art Unit 1634