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 .
Status of the Claims
Claims 1-19 are pending (claim set as filed on 03/01/2024).
Priority
This application is a 371 of PCT/CN2022/079854 filed on 03/09/2022, which has a foreign application to CN 202111019944.X filed on 09/01/2021.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 03/01/2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the Examiner.
Drawings
The drawings filed on 03/01/2024 have been accepted.
Claim Rejections - 35 USC §112, Indefinite
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.
Claims 2-4 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 2-4 contains the trademark/trade name “Triton X-100”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name (MPEP 2173.05(u)).
Claim Rejections - 35 USC §103, Obviousness
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 non-obviousness.
Claims 1-19 are rejected under 35 U.S.C. 103 as being unpatentable over Matsumoto (Advanced CUBIC tissue clearing for whole-organ cell profiling, 2019) in view of Kojima (US 2020/0217761 A1) - references cited by the ISA and in the IDS filed on 03/01/2024.
Matsumoto’s general disclosure relates to tissue-clearing techniques and high-resolution volumetric imaging by light-sheet fluorescence microscopy (see page 3506: Introduction).
Matsumoto teaches an overview of the advanced CUBIC pipeline in whole-organ cell profiling which comprises three major stages (tissue clearing, imaging and image analysis) and a tissue expansion protocol for high-resolution imaging (see page 3507: Figure 1). In particular, Matsumoto teaches delipidation, nuclear staining, RI matching, gel embedding, imaging (see Tables 1-2).
Regarding the delipidation reagent, Matsumoto teaches the reagent setup of CUBIC-L which is a mixture of 10% (wt/wt) N-butyldiethanolamine and 10% (wt/wt) Triton X-100 in dH2O (see page 3522, bottom ¶).
However, Matsumoto does not teach: initiate polymerization of the monomer molecules that permeate into the biological tissue sample to form a polymer gel.
Kojima’s general disclosure relates to “a method for rapidly clearing a biological tissue … a method for clearing a biological tissue, including the steps of: infiltrating the biological tissue with water soluble ethylenically unsaturated monomers before, during or after fixing the biological tissue with a fixative, wherein the water-soluble ethylenically unsaturated monomers include at least a water-soluble ethylenically unsaturated monomer having an ionically dissociable group; polymerizing the water-soluble ethylenically unsaturated monomers to form a hydrogel in the fixed biological tissue; and removing a lipid from the fixed biological tissue” (see abstract & Examples).
Regarding the solvent, Kojima teaches “a solvent used in the monomer solution may be saline or a buffered saline. The buffer solution may be appropriately selected from those known in the art, and may be, for example, a phosphate buffer solution, a borate buffer solution, a Tris-hydrochloride buffer solution, a citrate buffer solution, a carbonate buffer solution, a succinate buffer solution, an acetate buffer solution or the like” (see ¶ [0050]).
Regarding the cross-linking agent, Kojima teaches the monomer solution preferably contains a nonionic surfactant (see below; such as Tween 20, Triton X-100 or saponin). The concentration (mass/volume) of the monomers in the solution is not particularly limited, and may be, for example, 0.5% to 10%, (see ¶ [0049]-[0060]). The monomer solution may contain a crosslinking agent wherein examples of the crosslinking agent include N,N'methylenebisacrylamide (see ¶ [0053]-[0055]).
Regarding the initiator, Kojima teaches “the monomer solution may contain a polymerization initiator for efficient polymerization reaction. The polymerization initiator may be a known one (for example, a thermal polymerization initiator or a photopolymerization initiator), and is preferably a thermal polymerization initiator, and more preferably an azo polymerization initiator” (see ¶ [0056]-[0059]).
Regarding the gel monomer, Kojima teaches “the following reagents were used in the present Examples: paraformaldehyde as a protein fixative; acrylamide (AA), sodium p-styrenesulfonate (SS), sodium 2-acrylamido-2-methylpropane sulfonate (AMPS) and acrylic acid (AcA) as monomers; N,N'-methylenebisacrylamide (bisAA;) as a crosslinking agent; 2,2'-azobis [2-(2-imidazolin-2-yl)propane]dihydrochloride” (see ¶ [0102]-[0112]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform a monomer soaking permeation and then gelation during gel permeation such as taught by Kojima in the method of Matsumoto. Since Matsumoto discloses that an agarose gel permeates into biological tissue for expansion, a person skilled in the art would have been motivated to use the gel permeation component of Kojima, so that gel permeation is performed after degreasing. Therefore, claimed invention would have been prima facie obvious to one of ordinary skill in the art following the guidance of the cited references.
Furthermore, if not expressly taught by the references, based upon the overall objective with respect maximizing efficiency of tissue clearing efficiency, the adjustments of particular conventional working conditions (e.g., the amount or concentration of the reagents used, or temperature) are deemed a matter of judicious selection and routine optimization which is within the purview of the skill artisan. “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation” (MPEP 2144.05(II)(A)). Therefore, the cited references establish the conditions of variable parameters such that one of ordinary skill in the art would recognize that these conditions are a result effective variable dependent upon the type of biological tissue to be imaged. This is motivation for someone of ordinary skill in the art to practice or test the parameter widely to find those that are functional or optimal which then would be inclusive or cover the steps as instantly claimed. Absent any teaching of criticality by the Applicant concerning said conditions, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are result effective variable which can be met as a matter of routine optimization (MPEP 2144.05 II).
Conclusion
No claims were allowed.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NGHI V NGUYEN whose telephone number is (571)270-3055. The examiner can normally be reached Mon-Fri: 9 - 3 pm (ET).
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653
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