DETAILED ACTION
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 Claims
Claims 1-12 as preliminarily amended are currently pending and subject to an election requirement.
Election/Restrictions
During a telephone conversation with Lawrence J. Crain on 3/02/2026 a provisional election was made with traverse to prosecute the invention of Group I, claims 1-7. Affirmation of this election must be made by applicant in replying to this Office action.
The traversal appears to be on the ground(s) that claimed inventions possess a priori unity of invention. This is not found persuasive because the claimed inventions lack unity of invention a posteriori because even though the inventions of these groups require the technical feature of the composition of claim 8, this technical feature is not a special technical feature as it does not make a contribution over the prior art cited below.
The requirement is still deemed proper and is therefore made FINAL.
Claims 8-12 are withdrawn, with traverse, from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Restriction is required under 35 U.S.C. 121 and 372.
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claims 1-7, drawn to a method of making giant extracellular vesicles from cells.
Group II, claim 8-10 and 12, drawn to a composition comprising giant extracellular vesicles.
Group III, claims 11, drawn to a method of screening the activity with a molecule of interest, the method contacting the giant extracellular vesicles of claim 8 with a molecule of interest.
Claim 8 is a product-by-process claim. Claims 9, 10, and 12 either depend from or incorporate the limitations of claim 8. The patentability of product-by-process claims depends only on the structure of the claimed composition or any structural differences imparted to the final product by method steps in a product-by-process claim. See M.P.E.P. § 2113. In the instant case and absent evidence to the contrary, a prima facie case exists that the composition claimed in the product-by-process claims is substantially or completely identical to the composition made by other methods. For the purposes of restriction, claims 8-10 and 12 are read as composition of matter claims for the statutory class of invention. See M.P.E.P. § 2106.
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons: Groups I-III lack unity of invention because even though the inventions of these groups require the technical feature of the composition of claim 8, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Grimmer et al. (Scientific Reports (2020), 10:3100; Reference U). Grimmer teaches a composition comprising giant endoplasmic reticulum vesicles (GERVs) and which further comprise organelles (Abstract).
Therefore, restriction is necessitated between Groups I-III.
Applicant is advised that the reply to this requirement to be complete must include (i) an election of an invention to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected invention.
The election of an invention may be made with or without traverse. To reserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the restriction requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Joint Inventors
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Rejoinder
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
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.
Claim 3 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 3 is in improper Markush form, as the claim lacks any terminal conjunction between “CHAPSO” and “magnesium.”; a Markush group should generally be in the form of either 1) “an agent selected from the group consisting of A, B, and C”, or 2) “wherein the agent is A, B, or C”. See M.P.E.P. § 2117. Currently, it is not clear which species are included in the Markush group and which are not. Correction is required.
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.
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.
Claims 1 and 4-7 are rejected under 35 U.S.C. 103 as being unpatentable over Grimmer et al. (Scientific Reports (2020), 10:3100; Reference U) in view of Oglęcka et al. (eLife (2014), 3, e03695; Reference V) and as evidenced by Wuestehube and Schekman (Methods in Enzymology (1992), 219, 124-136; Reference W).
Grimmer, citing the teachings of Wuestehube and Schekman, teaches a method of making a composition comprising giant endoplasmic reticulum vesicles comprising organelles (GERVs) and obtaining said vesicles (Abstract and Fig. 1), the method comprising 1) forming yeast spheroplasts by contacting the yeast cells with lyticase and chitinase, 2) osmotically lysing and homogenizing the yeast spheroblasts with a lysis buffer comprising 0.1 M sorbitol (and equating to about 100 mOsm/L), and 3) collecting the GERVs after two steps of differentiation centrifugation at 10 minutes each and a step of sucrose density fractionation (see Grimmer at p6, subheading “ER membrane preparation” and Wuestehube and Schekman at p125-127, subheading “Sucrose Density Gradient-Purified Membrane Preparation”), reading on steps (a) and (c) of claim 1, the embodiments of “in bulk” and yeast cells for the organisms of claim 4, the embodiments of homogenization for the mechanical force and the lysis buffer for the chemical agents of claim 6. Grimmer teaches that the membrane tension of the GERVs is tunable by the osmotic tension of pipette aspiration (p1, the paragraph starting “On the other hand…”), reading in-part on step (b) of claim 1. Grimmer teaches that the GERVs have a diameter range of 2-10 µm (Fig. 2), reading in-part on step (b) of claim 1 and reading on claim 5. Grimmer teaches transfecting the yeast cells with Sec12p-sfGFP as a marker of the endoplasmic reticulum (the paragraph spanning p5-6 and the green images in Fig. 4), reading on claim 7.
Regarding claim 5, Grimmer teaches the claimed surface (area)-to volume (SA:V) ratios based on the following calculations, wherein r = radius and approximated for a sphere or ball: 1) Surface area = 4 * π * r2, 2) Volume = (4/3) * π * r3, and so 3) SA:V is approximated as 3/r. 4) The GERV diameter range of 2-10 µm of Grimmer equates to r = 1 and r = 5 for the endpoints of the range, respectively, and so yields a SA:V ratio of about 0.6-3 µm-1, thus reading on claim 5.
Regarding claim 1 step (b), Gimmer does not teach applying a membrane tension of 10-3 to 5 mN/m for 10-4 to 100 seconds.
Oglęcka teaches that membrane tension of about 3-5 mN m-1 caused by contacting giant lipid vesicles with a composition comprising 200 mM sucrose (equating to 200 mOsm/L, and being hypotonic) is generally sufficient to induce membrane lysis in giant lipid vesicles (Abstract and p9-10, the paragraph starting “Consider a case…” through the paragraph ending “…(Portet and Dimova, 2010).”), reading on claim 1. Oglęcka teaches that giant lipid vesicles go through asynchronous swell-burst lytic cycles in hypotonic media from 0-247 seconds or 0-448 seconds (Abstract, Figure 2, and p3 the paragraph staring “A time-lapse video…), reading on claim 1.
Regarding membrane tension of claim 1, it would have been obvious to a person of ordinary skill in the art before the invention was filed to apply the membrane tension and time range of Oglęcka to the methods of Grimmer. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Oglęcka and Grimmer are in-part directed towards giant lipid vesicle compositions and contacting said vesicles with hypotonic compositions, and because Grimmer teaches that the membrane tension of the GERVs is expressly tunable by the osmotic tension of pipette aspiration The skilled artisan would have been motivated to do so because Oglęcka teaches that membrane tension of about 3-5 mN m-1 is predictably advantageous to induce membrane lysis and so would likely improve upon the cell lysis and methods of making a composition comprising giant endoplasmic reticulum vesicles comprising organelles of Grimmer.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 2 is rejected, and claims 1 and 4 are alternatively rejected, under 35 U.S.C. 103 as being unpatentable over Grimmer in view of Oglęcka and as evidenced by Wuestehube and Schekman as applied to claim 1 above, and further in view of Ansell et al. (US 2017/0119904; Reference A).
The teachings of Grimmer, Oglęcka and Wuestehube and Schekman are relied upon as set forth above.
Regarding claim 2, Grimmer, Oglęcka and Wuestehube and Schekman do not teach the embodiment of mixing the cells at a rate of 0.01-10 m/s for 0.01 seconds to 10 minutes
Ansell teaches methods of preparing lipid nanoparticles/vesicles from liver tissue, the method comprising obtaining a liver tissue sample, homogenizing the liver tissue at 2x6.0 m/s for 15 seconds (¶0159-0161), reading on claim 2.
Regarding claim 2, it would have been obvious to a person of ordinary skill in the art before the invention was filed to substitute the homogenization step of Ansell for the homogenization step of Grimmer as evidenced by Wuestehube and Schekman A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Ansell and Grimmer as evidenced by Wuestehube and Schekman are directed towards methods of making related lipid nanoparticle/vesicle compositions from eukaryotic cells. The skilled artisan would have been motivated to do so because the substitution would be predictably advantageous to yield a homogenization step with precisely defined operation parameters in the methods of Grimmer as evidenced by Wuestehube and Schekman.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Grimmer in view of Oglęcka and as evidenced by Wuestehube and Schekman as applied to claim 1 above, and further in view of Baghirova et al. (MethodsX (2015), 2, 440-445; Reference U2).
The teachings of Grimmer, Oglęcka and Wuestehube and Schekman are relied upon as set forth above. Grimmer further teaches quantitating organelle-specific protein markers by western blot and including against Nop9 as a nuclear membrane marker (p6, subheading “ER membrane preparation”), reading in-part on claim 3.
Regarding claim 3, Grimmer, Oglęcka and Wuestehube and Schekman do not teach the embodiment of SDS as a species of additional molecule.
Baghirova teaches methods of subcellular fractionating cells to isolate proteins of interest from the cytosol, membrane-bound organelles, and the nucleus (Abstract). Baghirova teaches three lysis buffers with increasing detergent strength, the third lysis buffer comprising sodium dodecyl sulfate (i.e. SDS) (Abstract and Table 1), reading on claim 3. Baghirova teaches that sodium dodecyl sulfate (i.e. SDS) is an anionic detergent that is extremely effective at membrane that when combined with sodium deoxycholate yields an effective nuclear lysis buffer (the paragraph spanning p442-443), reading on claim 3.
It would have been obvious to a person of ordinary skill in the art before the invention was filed to add the SDS of Baghirova to the methods of Grimmer in view of Oglęcka and as evidenced by Wuestehube and Schekman. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Baghirova and Grimmer are in-part directed towards methods of subcellular fractionating cells. The skilled artisan would have been motivated to do so because Baghirova teaches that the addition of a composition comprising SDS would be predictably advantageous as a nuclear lysis buffer and so would predictably enhance the methods of Grimmer by lysing the nucleus of Grimmer’s yeast cells to further detect the nuclear membrane marker, Nop9, of Grimmer.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Conclusion
No claims are allowed. No claims are free of the art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached at 571-272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Sean C. Barron/Primary Examiner, Art Unit 1653