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 .
Claim Status
Applicant’s amendment filed 3/19/2026 has been entered. Claims 1-14 are pending. Claim 11 is withdrawn. Claims 1-10 and 12-14 are examined herein.
Priority
Applicant is reminded that in order for a patent issuing on the instant application to obtain priority under 35 U.S.C. 119(a)-(d) or (f), 365(a) or (b), or 386(a) or (b), based on priority papers filed in a parent or related Application No. 16/304580 (to which the present application claims the benefit under 35 U.S.C. 120, 121, 365(c), or 386(c) or is a reissue application of a patent issued on the related application), a claim for such foreign priority must be timely made in this application. To satisfy the requirement of 37 CFR 1.55 for a certified copy of the foreign application, applicant may simply identify the parent nonprovisional application or patent for which reissue is sought containing the certified copy.
Election/Restrictions
Applicant’s election without traverse of the following distinct species in the reply filed on 3/19/2026 is acknowledged: Group A: CRISPR--associated proteins, claims 5-7 specifically read on this election; Group B: (i) a CRISPR-associated (Cas) polypeptide with intact nuclease activity, claim 6 specifically reads on this election; Group C: tetraspanins, claim 9 specifically reads on this election; Group D: serum starvation, claim 10 specifically reads on this election; and Group E: None required due to withdrawal of claim by Applicant.
Upon further consideration, hypoxia in claim 10 has been rejoined with the elected species.
The non-elected species in claims 5, 6, 9 and 10 and 11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/19/2026.
Drawings
The drawings are objected to because they are in color (Figure 14) but no petition to accept color drawings filed under 37 CFR 1.84(a)(2) or (b)(2) has been accepted. See MPEP 608.02, part VIII which states:
Color drawings and color photographs are not accepted in utility applications filed under 35 U.S.C. 111 unless a petition filed under 37 CFR 1.84(a)(2) or (b)(2) is granted. Color drawings and color photographs are not permitted in international applications (see PCT Rule 11.13 ).
Unless a petition is filed and granted, color drawings or color photographs will not be accepted in a utility patent application filed under 35 U.S.C. 111. The examiner must object to the color drawings or color photographs as being improper and require applicant either to cancel the drawings or to provide substitute black and white drawings.
The drawings are objected to for the following reasons:
37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG."” In the current case, the view numbers for Figures 1-14 are preceded by the word "Figure" instead of the abbreviation "FIG.".
37 C.F.R. 1.84 states “Character of lines, numbers, and letters. All drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined.” In the current case, the words in the X axis in Figure 12 are illegible.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The use of the terms OPTI-MEM™ (p. 36), NOVEX™ (p. 37), ODYSSEY® (p. 37), IMMOBILON® (p. 37), VIVAFLOW® (p. 37), ÄKTAPURE® (p. 38), HISCREEN™ (p. 38), HITRAP™ (p. 38), SEPHAROSE™ (p. 38), and AMICON® (p. 38) which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 1 and 4 are objected to because of the following informalities: claim 1, reciting “Evs” in line 8 appears to have a typographical error with the “v” in lower case; claim 4 appears to have a clerical error with “the” following “wherein” in line 1. Appropriate correction is required.
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 13 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 13 recites the limitation “wherein the purifying comprises a procedure selected from the group consisting of liquid chromatography (LC), bead-elute LC, size-exclusion LC, high-performance liquid chromatography (HPLC), spin filtration, tangential flow filtration, hollow fiber filtration, centrifugation, immunoprecipitation.” There is no “and” or “or” to indicate a proper Markush grouping of alternatives. The metes and bounds of the claim cannot be determined and are indefinite.
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.
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 1-4, 8-10 and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Wiklander et al. (WO2014168548A2; Cite No. 012 on IDS filed 7/6/2023), in view of Fong et al. (Trends in Biotech. 2015. Cite No. 021 on IDS filed 7/6/2023).
Wiklander’s disclosure is directed to therapeutic delivery vesicles, for instance exosomes or microvesicles, comprising polypeptide constructs, methods for producing said therapeutic delivery vesicles, pharmaceutical compositions and medical uses thereof (Technical Field; entire document).
Regarding claims 1-4 and 14, Wiklander teaches methods of producing therapeutic EVs comprising introducing into an EV-producing cell at least one polynucleotide construct comprising at least one polynucleotide construct comprising at least one polypeptide construct comprising at least one polypeptide of interest into a cell capable of producing exosomes and collecting (harvesting) at least one delivery vesicle produced by the cells and teaches increasing the yield of extracellular vesicles (p. 5, paras 3-4; p. 29, para 2; p. 42, para 3; Examples). Wiklander further teaches polynucleotide constructs comprising exosomal proteins to transport a polypeptide construct to a suitable vesicular location (p.13, para 2).
However, Wiklander does not teach the polypeptide construct comprising an endogenously activatable polypeptide-based release system.
Regarding claims 1-4 and 14, Fong teaches self-cleaving intein-based tags that can be used to release the PoI (p. 273, right column, para 1; p. 274, Fig. 1 and pages 273-275). Fong teaches the advantages of self-cleaving intein-based tags in protein production in bacteria and eukaryotes (p. 276, right column, paras 3-4).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Wiklander’s EVs and method of producing EVs by adding the intein release system of Fong in order to improve therapeutic delivery because it would have amounted to a simple combination of prior art elements according to known methods to yield predictable results. One would have had a reasonable expectation of success because Wiklander and Fong are directed to improvements in EV delivery of therapeutic proteins.
Thus, the claimed invention as a whole is prima facie obvious.
Regarding claims 8-9, Wiklander teaches exosomal polypeptides selected from the tetraspanins CD9, CD63, and CD81 (Examples).
Regarding claim 10, Wiklander teaches stress-inducing culturing conditions such as serum starvation and hypoxia (p. 36, para 3; claims 16-17).
Regarding claims 12-13, Wiklander teaches purifying EVs by ultrafiltration and by size exclusion liquid chromatography (claim 13).
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Claims 5-7 are rejected under 35 U.S.C. 103 as being unpatentable over Wiklander et al. (WO2014168548A2; Cite No. 012 on IDS filed 7/6/2023), in view of Fong et al. (Trends in Biotech. 2015. Cite No. 021 on IDS filed 7/6/2023), as applied to claims 1-4, 8-10 and 12-14 above, and further in view of Wang et al. (CRISPR/ Cas9 in genome editing and beyond. Annual review of biochemistry, 85(1), pp.227-264; published 4/25/2016).
The teachings of Wiklander and Fong are applied to claims 5-7 as they have been applied to claims 1-4, 8-10 and 12-14 in the 103 discussion above.
Wiklander further teaches exosomes comprising therapeutic polypeptides comprising receptors (p. 20, para 3) and to deliver treatment of diseases and disorders (p. 23, para 3; and p. 38, para 2).
However, Wiklander and Fong do not specifically teach that the protein of interest is a therapeutic polypeptide selected from CRISPR-associated proteins (claim 5), (i) a CRISPR-associated (Cas) polypeptide with intact nuclease activity or (ii) a catalytically inactive CRISPR-associated (Cas) polypeptide (claim 6), or a catalytically inactive CRISPR-associated (Cas) polypeptide capable of enabling targeted genetic engineering (claim 7).
Wang’s disclosure is directed to genome editing, regulation, and imaging with CRISPR/Cas9 (entire document).
Regarding claims 5-6, Wang teaches vectors encoding Cas9 or catalytically inactive dCas9 can be delivered for gene editing therapies and regulation (pp. 236-242; Fig. 3; pp. 250-252).
Regarding claim 7, Wang teaches that catalytically inactive dCas9 can be used for targeted genetic engineering (Fig. 1; pp. 232-233).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Wiklander and Fong’s method of producing EVs comprising therapeutic polynucleotides encoding therapeutic polypeptides with Wang’s Cas9 and catalytically inactive dCas because it would have amounted to simple substitution of known therapeutic polypeptides to obtain predictable results of treating a disease or disorder by genetic engineering. One would have had a reasonable expectation of success because Wiklander, Fong, and Wang are directed to improved compositions and methods of genetic engineering and delivering therapeutics. Thus, the claimed invention as a whole is prima facie obvious.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHALEDA B HASAN whose telephone number is (571)272-0239. The examiner can normally be reached IFP, Monday - Friday 7:30am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KHALEDA B HASAN/Examiner, Art Unit 1636
/BRIAN WHITEMAN/Primary Examiner, Art Unit 1636
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