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 .
This action is responsive to the most recent claim set, filed on Aug. 14, 2024. Claims 1-10 are pending and examined below.
Priority
The present application is a 35 U.S.C. 371 national stage filing of the International Application No. PCT/KR2021/020063, filed Dec. 28, 2021, which claims foreign priority 35 U.S.C. 119(a)-(d) to Korean Application No. KR10-2020-0185554 filed on Dec. 29, 2020.
Thus, the earliest possible priority for the instant application is Dec. 29, 2020.
Information Disclosure Statement
The information disclosure statement filed June 27, 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 § 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 1-10 are 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.
The terms “protein-friendly material” and “positive charge-friendly material” in claim 1 are relative term which renders the claim indefinite. The term is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. While claim 8 indicates some materials that are considered “protein-friendly material” and “positive charge-friendly material,” the scope of the limitation is not deemed to be limited to these and it is not clear exactly how “protein-friendly” a material must be to qualify as a “protein-friendly” material, or how “positive charge-friendly” a material must be to qualify as a “positive charge-friendly material.”
Claim 9 is further rejected as it recites “performed by treating a buffer…,” which does not make sense.
For the purpose of examination, claim 9 is interpreted as reciting “performed by treating with a buffer…”
Claim 10 is further rejected as it recites the limitation "a buffer of (e)". As no buffer is recited in step (e), this limitation is indefinite.
For the purposes of examination, claim 10 is interpreted as being dependent on claim 9, and reciting “the buffer…”.
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.
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) 1-4, 7 and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Carter et al. (WO 2020/077294 A1) in view of Lee et al. (EP 3 660 143 A2).
The claims are directed to methods of isolating exosomes from a sample including the steps of (a) deproteinizing the sample; (b) treating the deproteinized sample with a buffer to aggregate the exosomes; (c) binding the exosomes to a membrane; (d) centrifuging and washing the exosomes; and (e) isolating the washed exosomes through a neturalization reaction. Note that as the specification does not provide a specific definition, “neutralization” is being interpreted broadly as any step that neturalizes in any way the exosomes, thereby enabling any level of isolation.
Carter et al. teach a method for isolation and purification of exosomes including a pre-filtration step on the exosome-containing sample, which allows larger molecules (including large proteins) to be retained, while the exosomes pass through (step a); the exosome-containing filtrate is then contacted with a second, capture membrane, which binds the EVs (step c); the capture membrane (with EVs) undergoes low centrifugation (step d); then an optional washing; and the EVs are eluted from the capture membrane using a PBS+EDTA solution (step e). (pg. 12, ll. 9-15; pgs. 17-19, Ex. 3).
Carter et al. do not teach deproteinizing the sample (step a).
Lee et al. teach a method for isolating exosomes that includes pre-treating an exosome solution by centrifuging and precipitating (salting out, which would remove protein and DNA – Fig. 2, “pre-clearing”; paras. [0033]-[0036], or pre-treating with various methods – paras. [0043]-[0044]) (step a); adding PEG to precipitate and aggregate the exosomes (step b); various buffers are added, with each of them tested with a corresponding HIC column washed with the buffer (step c); the column with bound EVs is centrifuged and the EVs are eluted, for example when the NaCl concentration reaches 0M. (Examples 1, 3 & 4; para. [0057], [0076], [0078]; claim 1).
It would have been obvious for one of ordinary skill in the art at the time of the invention to have modified the exosome isolation process of Carter et al. to incorporate a pre-clearing step to remove proteins because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Incorporating this modification would have led to predictable results with a reasonable expectation of success because both Carter et al. and Lee et al. teach methods for isolation of exosomes and this initial, pre-treatment step could be applied to any/all methods of isolating exosomes, as it functions as a sample preparation step, undertaken prior to moving on to the exosome isolation protocol.
With respect to claim 2, Carter et al. teach pre-filtration membrane within the claimed range (0.2 µm – 1 µm), rendering obvious using a syringe filter with this pore size.
With respect to claims 3 and 4, Lee et al. teach PEG is used in the claimed concentration. (para. [0078]).
With respect to claims 7 and 9-10, Lee et al. teach adjusting the buffer of the pH (between 3 and 12) to accomplish the desired result, and using appropriate buffers, including phosphate-based buffers, rendering obvious the claimed pH and monosodium phosphate. (para. [0052], [0041]).
Claim(s) 5 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Carter et al. (WO 2020/077294 A1) in view of Lee et al. (EP 3 660 143 A2), as applied to claims 1-4, 7 and 9-10 above, and further in view of Ellis et al. (Trends Biochem Sci, 2001).
Carter et al. as modified by Lee et al. teach the use of PEG in the claimed concentration, but do not teach using 0.01 -10% (w/v) dextran or PEI.
These would have been art-recognized substitutions for PEG, as each of these functions as a macromolecular crowding agent in buffer and selection of such an agent enables in vitro mimicking of the intracellular environment, and, as of, 2001, this was a “routine variable to study” (Ellis et al., abstract). See MPEP 2144.06
Claim(s) 8 is rejected under 35 U.S.C. 103 as being unpatentable over Carter et al. (WO 2020/077294 A1) in view of Lee et al. (EP 3 660 143 A2), as applied to claims 1-4, 7 and 9-10 above, and further in view of Tamba et al (Chemistry Physics Lipids, 2011).
Carter et al. in view of Lee et al. does not explicitly teach the use of the claimed material for the protein-friendly or positive-charge material.
These would have been obvious substitutions as these are commonly used materials in this field and selecting one of the claimed materials would not have involved an inventive step for one of skill in the art. (See generally Tamba et al. - teaches the use of polycarbone membranes for filtering purification of giant unilammelar vesicles, pg. 352, 2nd col, 1st full para.).
Conclusion
No claims are allowed.
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/TERESA E KNIGHT/ Primary Examiner, Art Unit 1634
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