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 Application, Amendments and/or Claims
Claims 1-20 are pending.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-17, drawn to a composition comprising extracellular vesicles and a carrier, in the reply filed on 20 October 2025 is acknowledged. The traversal is on the ground(s) that the search and examination of the subject matter of all the pending claims would not constitute a serious burden. Applicant argues that all pending claims recite at least the following common element: extracellular vesicles derived from a condition medium collected from differentiated epithelial cells, cultures at an air-liquid interface in a nutrient medium sufficient to meet the nutritional needs required to grow the cells in vitro to form the differentiated epithelial cells. Applicant contends that the search and examination of Groups I, II, and III would at least partially overlap, thereby easing the burden on the Examiner. Applicant adds that because independent claims share common elements, it is highly likely that a search for Group I would also yield pertinent art to Groups I and III. This is not found persuasive.
Specifically, as discussed at pages 3-4 of the previous Office Action of 18 July 2025, the extracellular vesicle composition of Group I can be used in materially different methods from the treatment method of Group III, such as in immunoassays or cells culture assays. Furthermore, the method of making a composition of Group II can be used to make a materially different product from that of Group I. For example, the process of Group II could be used to make compositions that comprise extracellular vesicles or other cellular components derived from different cells or tissues. Applicant is reminded that there would be a serious search and/or examination burden (if restriction were not required) because the inventions of Groups I-III require a different field of search (as the inventions are composed of different structures and methods) and the inventions are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. The inventions of Groups I, II, and III have also acquired a separate status in the art in view of their different classifications (A61K 8/14 and A61Q 19/00, for example).
The requirement is still deemed proper and is therefore made FINAL.
Claims 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 20 October 2025.
Claims 1-17 are under consideration in the instant application.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06 May 2025; 14 March 2024; 11 December 2023; and 14 November 2022 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
1. The disclosure is objected to because of the following informalities:
1a. In the specification at page 12, [0028-0029], the headings for “FIG. 2” and “FIG. 3” should each refer to figure subparts A-D (i.e., “FIG. 2A-2D” and “FIG. 3A-3D”).
1b. The Brief Description of the Drawings at pages 12-13, [0030-0031], does not refer to Figures 4A-4D or Figures 5A-5D in the headings or figure descriptions.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
2. Claims 1-17 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.
2a. Claims 1-17 are rejected as being indefinite because the following underlined phrase in claim 1, lines 3-5 is not clear: “wherein the extracellular vesicles are derived from a condition medium collected from differentiated epithelial cells, cultured at an air-liquid interface in a nutrient medium sufficient to meet the nutritional needs required to grow cells in vitro to form the differentiated epithelial cells”. First, what cells or tissues are cultured at an air-liquid interface? It is not clear if the differentiated epithelial cells in line 3 are cultured at the air-liquid interface because the end of the claim also recites “required to grow cells in vitro to form the differentiated epithelial cells” (emphasis added by the Examiner). If the “grow cells” refers back to the differentiated epithelial cells recited in line 3, then the “required to grow cells in vitro…” limitation in line 4 is even more confusing (i.e., “cultured at an air-liquid interface in a nutrient medium sufficient to meet the nutritional needs required to grow [differentiated epithelial] cells in vitro to form the differentiated epithelial cells”). How does the differentiated epithelial cell form itself? Furthermore, line 2 of claim 1 recites a “conditioned medium” while line 3 also recites a “nutrient medium”. Are these the same medium or two different mediums?
2b. Claim 11 is rejected as being indefinite because line 2 recites the phrase “for at least about 3 hours”. The phrase “at least about 3 hours” 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. Specifically, there is no indication in the specification as to what range of hours or minutes is encompassed by culturing differentiated epithelial cells “at least about 3 hours”.
2c. Claims 15 and 16 are rejected as being indefinite because the first line of each claim simply recites “[t]he composition of claim 1, comprising a population of CD9 positive extracellular vesicles”. It is not clear if the CD9 positive extracellular vesicles are intended to further limit the “extracellular vesicles” recited in claim 1. Or, is the population of CD9 positive extracellular vesicles an additional/further element of the composition (i.e., a composition comprising extracellular vesicles, a carrier, and a population of CD9 positive extracellular vesicles)? One of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Please note that if Applicant intends claims 15 and 16 to further limit the extracellular vesicles of claim 1, the claims could be amended to recite, for example, “The composition of claim 1, wherein the extracellular vesicles are CD9 positive extracellular vesicles”.
2d. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 17 recites the broad recitation “biologics”, and the claim also recites “small molecules”, “therapeutic agents”, “preservatives”, and “enzymes” which is the narrower statement of the limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Improper Markush Grouping
3. Claim 17 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of “additional components” is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
Claim 17 recites the composition of claim 1, wherein the composition further comprises at least one additional component chosen from small molecules, biologics, therapeutic agents, preservatives, and/or enzymes. However, the recited “component” alternatives are not members of the same physical or chemical class and not disclosed or known in the prior art to be functionally equivalent and have a common use. There is no common core structure shared by all the recited components and there is no description in the specification of a shared function or biological activity of the components. For example, a preservative is a natural or synthetic chemical that is added to products to prevent decomposition by microbial growth or by undesirable chemical changes (see Shitole et al. Icon Res Engin J 5(7): 131-140, 2022; page 1, column 1). Meanwhile, an enzyme is an organic catalyst that (i) only acts on specific substrates and (ii) is produced by living cells that change the rate of chemical reactions without needing an external energy source or being charged themselves (see definition of “enzyme” from Taber’s Medical Dictionary; https://www.tabers.com/tabersonline/view/Tabers-Dictionary/737510/all/enzyme; accessed 21 November 2025).
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
4. Claims 2-12 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Instant claim 1, from which claims 2-12 depend, recites a composition comprising extracellular vesicles and a carrier, wherein the extracellular vesicles are derived from a condition medium collected from differentiated epithelial cells, cultured at an air-liquid interface in a nutrient medium sufficient to meet the nutritional needs required to grow the cells in vitro to form the differentiated epithelial cells.
However, claims 2-12 do not further limit the claimed subject matter of claim 1. For example, claims 2-12 do not recite any limitations that further limit the claimed composition, extracellular vesicles, or carrier. Claims 2-12 only recite limitations directed to differentiated epithelial cells, culture conditions, or conditioned media. It is also noted that the invention of claim 1 is a product and not a method.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
5. Claims 1-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Takano et al. (J Dermatol 47: 265-276, 2020).
Takano et al. teach a composition comprising exosomes (extracellular vesicles) and phosphate buffered saline (PBS) (a carrier), meeting the limitations of instant claim 1 (page 265, column 2, 1st full paragraph; page 266, column 2, 2nd and 3rd full paragraphs). Takano et al. disclose that the exosomes are derived from a conditioned medium collected from keratinocytes, meeting the limitations of instant claim 1 (page 266, column 2, 2nd and 3rd full paragraphs; page 267, column 1, last paragraph). Takano et al. teach that the exosomes are positive for CD9, CD63, and CD81, meeting the limitations of instant claims 15 and 16 (page 268, column 1, last paragraph through column 2; Figure 1b). Takano et al. disclose a composition comprising keratinocyte-derived exosomes and a MEK inhibitor, such as SH-6, H-89, PD98059, or SB203580, meeting the limitations of instant claim 17 (page 268, bottom of column 2; page 271, columns 1-2; Figure 2).
Applicant is reminded that determination of patentability is based on the product itself (MPEP §2113(I)). “The patentability of a product does not depend on its method of production. If the product in a product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process” (MPEP §2113(I); In re Thorpe, 777 F.2d 695, 227 USPQ964, 966 (Fed. Cir. 1985). The composition comprising exosomes and a carrier of Takano et al. appear to be structurally identical to the composition comprising extracellular vesicles and a carrier of the instant claims.
6. Claims 1-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhao et al. (J Mol Hist 48: 121-132, 2017).
Zhao et al. teach a composition comprising exosomes (extracellular vesicles) and phosphate buffered saline (PBS) (a carrier), meeting the limitations of instant claim 1 (page 122, column 1, 1st full paragraph; page 122, column 2, 3rd full paragraph). Zhao et al. disclose that the exosomes are derived from a conditioned medium collected from differentiated human amniotic epithelial cells, meeting the limitations of instant claim 1 (abstract; page 122, column 2, 2nd and 3rd full paragraphs). Zhao et al. teach that the exosomes are positive for CD9, CD63, and CD81, meeting the limitations of instant claims 15 and 16 (page 123, top of column 1; page 124, column 2, 2nd full paragraph; Figure 2). Zhao et al. also state that exosomes are resuspended in diluent C and mixed with PKH26, meeting the limitations of instant claim 17 (page 123, column 1, 1st full paragraph; page 124, column 2, 3rd full paragraph). Zhao et al. teach that the PKH26-labeled exosomes are co-cultured with fibroblasts in FBS-free medium, meeting the limitations of instant claim 17 (page 123, column 1, 1st full paragraph; page 124, column 2, 3rd full paragraph).
Applicant is reminded that determination of patentability is based on the product itself (MPEP §2113(I)). “The patentability of a product does not depend on its method of production. If the product in a product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process” (MPEP §2113(I); In re Thorpe, 777 F.2d 695, 227 USPQ964, 966 (Fed. Cir. 1985). The composition comprising exosomes and a carrier of Takano et al. appear to be structurally identical to the composition comprising extracellular vesicles and a carrier of the instant claims.
Conclusion
No claims are allowable.
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BEB
Art Unit 1647
20 November 2025
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647