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
Claims 1-2, 4-5, 7 and 9-16 are pending.
Claims 10-11 are withdrawn.
Claims 1-2, 4-5, 7, 9 and 12-16 are under examination.
Election/Restrictions
Applicant’s election with traverse of the following invention
Invention I, claims 1-2, 4-5, 7, 9 and 12-16 drawn to a cell repair-promoting extracellular vesicle, formed by silicate-induced secretion of stem cells, classified in A61L2300/626,
in the reply filed on 4th, August, 2026, is acknowledged.
Applicant’s traversal is on the grounds that “the Examiner has not indicated all of the criteria which are necessary for a proper requirement for restriction, including the existence of serious burden to the Examiner for the search and examination” (pg. 5-6).
In response, Inventions I-II encompass different classifications as set forth in the previous Restriction requirement, and therefore would require different search queries. Furthermore, the examiner was able to find art that satisfied the limitations of elected Invention I without satisfying the limitations of Invention II, therefore evidencing a search burden.
Furthermore, serious search and examination burden applies to all aspects of examination. Applicant is directed MPEP 803 (II) which states that for purposes of the initial requirement, a serious search burden on the examiner may be prima facie shown by appropriate explanation of separate classification, or separate status in the art, or a different field of search as defined in MPEP § 808.02. Similarly, a serious examination burden, for example, may be prima facie shown by appropriate explanation of non-prior art issues under 35 U.S.C. 101, pre-AIA 35 U.S.C. 112, first paragraph, and/or 35 U.S.C. 112(a) relevant to one invention that are not relevant to the other invention. In the instant case, the method of Invention II requires consideration under 35 U.S.C. 112(a) for non prior-art issues that are not relevant to the product of Invention I and the products of Inventions I requires consideration under 35 U.S.C. 101 for non prior-art issues that are not relevant to the method of Invention II.
Therefore, the Inventions pose a serious search and examination burden as defined in MPEP § 808 under proper 35 U.S.C. 121 restriction practice
The requirement is still deemed proper and is therefore made FINAL.
Claims 10-11 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.
Objections to Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (http://www.mirbase.org/ pg. 12). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http://, www or other browser-executable code. See MPEP § 608.01.
Objection to Drawings
Color photographs and color drawings have been noted in this Application (Figure 4C, Figure 8, Figure 10).
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Objections
Claims 2 and 12-14 are objected to because of the following informalities:
Claim 2 recites “the stem cells” while claim 1, upon which claim 2 depends, recites “human adipose-derived stem cells (ADSCs).” While is clear that “the stem cells” refers back to the human adipose-derived stem cells because they are the only previously recited stem cells, it is recommended that Applicant amend claim 2 to refer to the “human adipose-derived stem cells (ADSCs)” to improve the clarity and readability of the claims.
Claim 2 recites “the stem cells are cultured in a silicate culture medium containing a silicate component.” While it is clear this recitation intends to further limit the silicate-induced secretion, it is recommended that Applicant amend to directly refer to the silicate-induced secretion to improve the clarity and readability of the claims. A way to do this would be to amend to “wherein the silicate-induced secretion comprises a step of culturing the ADSCs in a silicate culture medium containing a silicate component.”
Claim 12 recites “31after” which is missing a space and would be correctly written as “31 after.” Claim 12 recites “the extracellular vesicle comprises a membrane surface potential lower than -15 mV and a total content of protein more than 4 μg/109.” However, these limitations are already recited in claim 1, upon which claim 12 depends, and it is therefore unnecessarily redundant to include them in claim 12.
Claim 12 recites “formed by silicate-induced as claimed in claim 1” which is missing a noun and appears to refer to “silicate-induced secretion.”
Claims 12 and 13 each recite “and cells showed significant expression of the miRNA-31 after cultured with the cell repair-promoting preparation then the cells without treatment from the cell repair-promoting preparation.” While it is clear this recitation intends to refer to a property of the extracellular vesicles, it is recommended that Applicant amend the wherein clause to recite a contingent limitation that requires this property to improve the clarity and readability of the claims. An example of a possible amendment would be to “wherein cells show significant expression of miRNA-31 after culturing with the cell repair-promoting preparation as compared to cells without treatment from the cell repair-promoting preparation.”
Claim 14 recites the range “109-1014 particles/mL” which appears to be a typographical error for “109-1014 particles/mL.”
Appropriate correction is required.
Claim Rejections - 35 USC § 101
Non-statutory Subject Matter
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 15-16 do not fall within at least one of the four categories of patent eligible subject matter because the claims are “use” claims that do not purport to claim a process, machine, manufacture, or composition of matter (see MPEP 2173.05(q)).
Claim 15 recites a use “a use of the preparation for wound repair,” and claim 16 recites both “The use according to Claim 15” and “used for repairing wounds caused by diabetes which are difficult to treat” and therefore these claims recite a use, but fail to recite steps (see MPEP 2173.05(q) (I)). Therefore, it is not apparent whether instant claims are directed to a product with intended uses or a method, and instant claims 15-16 do not fall within at least one of the four categories of patent eligible subject matter.
Claim Rejections - 35 USC § 101
Judicial Exception
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-2, 4-5, 7, 9, 12-13 and 15-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring product without significantly more.
Applicant is directed to the 2019 Revised Patent Subject Matter Eligibility Guidance published in the Federal Register (84 FR 50) on 1/07/2019, which is found at: https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf; and the October 2019 Update: Subject Matter Eligibility, which is found at https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_update.pdf.
Briefly summarized here, the new guidance cites a two part test: is the claimed invention directed to a statutory class of invention (Step 1), if so then is the claimed invention as a whole directed to a law of nature, natural phenomena, or an abstract idea (i.e. set forth or described in the claim) (Step 2A, prong one), if so then is the claimed invention recite additional elements that integrate the judicial exception into a practical application (Step 2A, prong two), if not then does the claim as a whole amount to significantly more than the judicial exception (Step 2B).
Step 1
In regard to step 1, the claims are directed to an extracellular vesicle and cell repair-promoting preparations including extracellular vesicles which are products and are a statutory class of invention. Accordingly, the requirements of step 1 are met.
Although, as set forth above, claims 15-16 are use claims that are not clearly drawn to a statutory category (see 35 U.S.C 101 rejection above), they are interpreted as encompassing intended uses of a product for this analysis.
Step 2A
In regard to step 2A prong one, as stated above, the claims are directed to cell repair-promoting preparations including extracellular vesicles.
Applicant is directed to the art of Chen et al. (Regen Biomater. 2020 Dec 3;8(1):rbaa038. eCollection 2021 Feb 1.; henceforth “Chen”). Chen evidences adipose-derived stem cells are a naturally occurring product (Materials and Methods “Isolation, culture and identification of ADSCs” pg. 2). Chen evidences extracellular vesicles released from adipose-derived stem cells (Materials and Methods “Separation and characteristics of hADSC-EVs” pg. 2).
Because extracellular vesicles are naturally released from cells, including adipose-derived stem cells, the extracellular vesicles are also a naturally occurring product.
Because extracellular vesicles are a product of nature, the claims are reviewed to determine if the product as claimed possesses markedly different characteristics (see MPEP 2106.04(c) for Markedly Different Characteristics Analysis).
Claims 1 and 12 each recite the following additional elements that do not impart markedly different characteristics for the reasons set forth below.
“cell repair-promoting” (instant claims 1 and 12)
This recites an intended use and does not impart a markedly different characteristic because the naturally occurring exosomes evidence by Chen are capable of meeting this intended use.
“silicate-induced secretion” (instant claim 1)
“formed by silicate-induced” (instant claim 12)
This is a product-by process limitation. Product-by process claims are not limited by the manipulation of the recited steps, only the structure implied by the steps. See In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (see MPEP 2113). Because the silicate-induced secretion does not appear to impart additional structure, it does not impart a markedly different characteristic.
“a membrane surface potential lower than -15 mV” (instant claims 1 and 12)
Applicant is directed to the art of Midekessa et al. (ACS Omega. 2020 Jun 30;5(27):16701–16710.; henceforth “Midekessa”). Midekessa evidences membrane surface potential (“zeta potential” or ZP) of extracellular vesicles is under negative charge in physiological conditions (pg. 16702 col. 2). All the measured values of extracellular vesicles at pH 7 (closest to physiologic pH) are less than -15 mV (see Figure 8), and are even lower at pH 10 indicating that physiologic pH of 7.4 would inherently have a membrane surface potential of the extracellular vesicles of less than -15 mV.
Furthermore, because it is noted that Midekessa evidences that zeta potential of extracellular vesicles is affected by buffer content, valency and ionic strength of the buffer, and pH levels Figures 6-8 and pg. 16704-16705), extracellular vesicles that are merely in a buffer would also not have markedly different characteristics because variation in membrane surface potential is a property of buffer optimization.
Claim 2 recites the additional element of “the stem cells are cultured in a silicate culture medium containing a silicate component”
Claim 4 recites the additional element of “the silicate is a calcium silicate”
Claim 5 recites the additional element of “the silicate culture medium comprises a culture medium, which comprises a mesenchymal stem cell medium (MSCM) or a Dulbecco' s modified Eagle's medium (DMEM)”
Regarding these elements of claims 2 and 4-5, these recite product-by process limitations that do not appear to impart a markedly different characteristic. See In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (see MPEP 2113 cited above)
Claim 9 recites the additional element “at least 40% of the extracellular vesicles express at least one of transmembrane proteins of CD9, CD63, or CD81”
Alptekin et al. (Immunol Rev. 2022 Jul 8;312(1):76–102; henceforth “Alptekin”) evidences almost all exosomes have CD63, CD9, and CD81 (pg. 3 and para.) and therefore this is a property inherent to naturally occurring exosomes and does not impart a markedly different characteristic.
Claims 12 and 13 each recite the additional element of “cells showed significant expression of the miRNA-31 after cultured with the cell repair-promoting preparation then the cells without treatment from the cell repair-promoting preparation” which is indefinite for the reason set forth below (see rejection under 35 U.S.C. 112b below) and therefore because this limitation is indefinite, it cannot impart a markedly different characteristic. This is interpreted as a conditional limitation and therefore because the naturally occurring extracellular vesicles have the required structures, this does not impart a markedly different characteristic.
Claim 13 recites the additional element of “a hydrogel carrying an extracellular vesicle formed by silicate-induced human adipose-derived stem cell secretion”
Naturally occurring extracellular matrix is not markedly different than engineered hydrogels and therefore this limitation reads on naturally occurring exosomes released into naturally occurring extracellular matrix and does not impart a markedly different characteristic.
Claims 15-16 each recite additional elements of uses which are interpreted as intended uses. How the composition is used does not impart a markedly different characteristic.
Therefore, the claims a whole are directed to the naturally occurring product of ADSC-derive extracellular vesicles.
Step 2A Prong Two
In regard to step 2A prong two, the claims do not recite additional elements that integrate the judicial exception into a practical application. As set forth above the additional elements recited by claims 1 and 12 do not differentiate from naturally occurring extracellular vesicles from ADSCs and therefore these additional elements also do not integrate the judicial exception into a practical application.
Furthermore, the recited additional elements do not integrate the judicial exception into a practical application for the reasons stated below.
Claims 1 and 12 each recites the additional element of “a membrane surface potential lower than -15 mV”
Because it is noted that Midekessa evidences that zeta potential of extracellular vesicles is affected by buffer content, valency and ionic strength of the buffer, and pH levels Figures 6-8 and pg. 16704-16705), zeta potential of extracellular vesicles appears to be a result of buffer optimization which is routine and conventional does not integrate into a practical application
Claim 1 and 12 each also recites the indefinite limitation of “a total content of protein more than 4 μg/109” which also does not integrate into a practical application because loading protein into an exosome for therapeutic purposes is well understood, routine and conventional and furthermore loading to a specific amount represents routine optimization which is also well understood, routine and conventional.
Claim 7 recites the additional element of “the membrane surface potential is between -20 m V and -30 m V” which does not integrate into a practical application because zeta potential of extracellular vesicles appears to be a result of buffer optimization which is routine and conventional and merely placing the vesicle in a buffer does not integrate into a practical application.
Claims 12 recites the additional element of “cells showed significant expression of the miRNA-31 after cultured with the cell repair-promoting preparation then the cells without treatment from the cell repair-promoting preparation” which is indefinite for the reason set forth below (see rejection under 35 U.S.C. 112b below) and therefore because this limitation is indefinite, it cannot integrate into a practical application. This is interpreted as a conditional limitation and merely being capable of meeting a contingent limitation does not integrate into a practical Application.
Claim 13 recites the additional element of “a hydrogel carrying an extracellular vesicle formed by silicate-induced human adipose-derived stem cell secretion”
Chen evidences hydrogel mixture is a current method to load extracellular vesicles (pg. 2 col. 1 2nd para.) and therefore merely loading the extracellular vesicle in a hydrogel would be well understood, routine, and conventional and not integrate into a practical application.
Claims 15-16 each recite additional elements of uses which are interpreted as intended uses. How the composition is used does not integrate into a practical application.
Step 2B
Regarding step 2B, the claims as a whole do not amount to significantly more than the judicial exception. As stated above, all the additional recited elements either do not impart a markedly different characteristic, do not integrate into a practical Application, or both. Since no further elements are recited, the claims as a whole do not amount to significantly more than the judicial exception.
Judicial Exception - Conclusion
Therefore, the claims are directed to a naturally occurring product (natural extracellular vesicles from ADSC) that is not integrated into a practical application, does not include elements that amount to significantly more than the judicial exception, and do not qualify as patent eligible subject matter under 35 U.S.C. § 101.
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.
Claims 1-2, 4-5, 7, 9 and 12-16 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.
Claims 1 and 12-13 each recite “a total content of protein more than 4 μg/109” which does not recite a unit for 109 and therefore makes the scope of the claim indefinite because it is unclear what the metes and bounds of “109” encompasses and therefore it is unclear what the measurement refers to.
By nature of their ultimate dependency on claim 1, claims 2, 4-5, 7, 9 and 15-16 are also rejected because they do not clarify the issue.
Claim 5 contains the trademark/trade name DMEM. 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) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). 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. In the present case, the trademark/trade name is used to identify/describe a basal cell culture media and, accordingly, the identification/description is indefinite.
Because this reagent was developed by the manufacturer at the time of the applicant’s invention under the trade name DMEM and as a result is proprietary, which means what constitutes as DMEM can change, and these changes do not need to be disclosed by these companies to the public. Accordingly, the identification of the trade name is indefinite and the applicant is advised to employ a sequence, the SeqID, IUPAC name and/or CAS number for this agent.
MPEP 2173.05(u) states that if 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 the 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). See also Eli Lilly & Co. v. Apotex, Inc., 837 Fed. Appx. 780, 784-85, 2020 USPQ2d 11531 (Fed. Cir. 2020).
Regarding the status of DMEM as a trademark, Applicant is directed to MPEP 608.01(v) which defines a trademark as follows:
The term "trademark" includes any word, name, symbol, or device, or any combination thereof-
(1) used by a person, or
(2) which a person has a bona fide intention to use in commerce and applies to register on the principal register established by this chapter,
to identify and distinguish his or her goods, including a unique product, from those manufactured or sold by others and to indicate the source of the goods, even if that source is unknown.
Although the Trademark for DMEM (number 98618988) was abandoned, it still meets the definition of a trademark according to the MPEP because it is a term “which a person has a bona fide intention to use in commerce” “to identify and distinguish his or her goods.” Since the trademark Application was filed (i.e. “applies to register on the principal register” MPEP 608.01(v) above), it falls under the definition of a trademark, even if the Trademark Status is now Dead/Abandoned.
Accordingly, for the reasons stated above, the claims are indefinite due to the presence of the trademark term “DMEM.”
Claim 5 recites “the silicate culture medium,” however, claim 1, upon which claim 5 depends, does not recite a silicate culture medium. Therefore, there is improper antecedent basis for this term and the metes and bounds of the claim are unclear because it is unclear how the silicate culture medium is intended to be incorporated into the extracellular vesicle of claim 1, upon which claim 5 depends.
Claim 7 is an orphaned claim that is dependent on cancelled claim 6. Therefore, the metes and bounds of this claim are indefinite because it is unclear how the limitations recites in claim 7 are incorporated into a prior claim.
Claim 14 is vague and indefinite in the use of parenthesis, since it is unclear whether the parenthetical material is or is not intended to be part of the claim.
Claim 15 recites “A use of the preparation for wound repair,” but fails to but fails to recite steps which renders the claim indefinite (see MPEP 2173.05(q) for “Use Claims”). First, because the claim fails to recite steps, the scope of the claim is indefinite because it is unclear what the scope encompasses. Additionally, claim 14 depends on claim 1 which is a product and therefore claim 14 includes both a product and a method of using and is indefinite. See In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1318, 97 USPQ2d 1737, 1748-49 (Fed. Cir. 2011).
Claim 16 is also rejected by nature of its dependency on claim 15 and because it does not clarify the issue.
Claim 16 recites the subjective term “difficult” with no corresponding definition. Therefore the scope of the claim is unclear. A claim may be rendered indefinite by reference to subjective term (see MPEP 2173.05(b), IV). Specifically, the term “difficult” is a subjective phrase which renders the claim indefinite. The term is not defined by the claim, the specification does not provide a standard for some standard for measuring the scope of the term, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention
Generally, when the claims are indefinite, vague or unclear, they cannot be construed without speculation or conjecture; therefore, the indefinite claims are not treated on the merits with respect to prior art. See In re Steele, 305 F.2d 859, 862 (CCPA 1962) (A prior art rejection cannot be sustained if the hypothetical person of ordinary skill in the art would have to make speculative assumptions concerning the meaning of claim language.); see also In re Wilson, 424 F.2d 1382, 1385 (CCPA 1970) ("If no reasonably definite meaning can be ascribed to certain terms in the claim, the subject matter does not become obvious-the claim becomes indefinite."). Notwithstanding Steele, the Office has made every attempt to construe the claims in what the Office believes is the intent of the Applicants in the interest of compact prosecution.
Claim Interpretation
Due to the 112b issues identified above, for the sake of compact prosecution, the claims identified with 112b issues above are being examined against the prior art and for double-patenting as follows:
The “a total content of protein more than 4 μg/109” recited in claims 1 and 12-13 is interpreted as more than 4 x 10-9 µg (equal to 4 μg divided by 109).
The limitations of claims 2 and 5 are interpreted as intending to further limit the product-by process limitation of “silicate-induced secretion” recited in claim 1.
Orphaned claim 7 is interpreted as depending on independent claim 1.
The use claims of claims 15 and 16 are interpreted as intended uses.
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.
Claims 1-2, 4-5, 7, 9, 12, and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Ofir et al. (US-20230190822-A1; published 22nd, June 2023 with PCT filed 5th, May, 2021).
Regarding claims 1 and 12, Ofir discloses an extra cellular vesicle formed by section of human adipose-derived stem cells (ADSC) (human ASC from adipose tissue; para. [0021, 0085, 0131]),
Wherein the extracellular vesicle comprises a membrane surface potential of -37 or -38 mV which is lower than -15mV (Table 2); and
a total content of protein of calculated µg of protein per exosome from Table 3 of from 3.09 x 10-9 µg (sample P3) to 3.60 x 10-9 µg (sample R6) (Table 3). The upper value of this range of 3.60 x 10-9 µg is very close to the lower value of the claimed range of slightly more than 4 x 10-9 µg (equal to 4 μg divided by 109).
Regarding claims 1 and 12, Applicant is directed to MPEP section 2144.05 which states a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). In the instant case, the taught values of 3.60 x 10-9 µg is so close to the claimed more than 4 x 10-9 µg (which encompassed slightly more than 4 x 10-9 µg) that one of ordinary skill would have expected them to have the same properties.
Regarding claims 1 and 12, concerning the preambles of claims 1 “a cell repair-promoting extracellular vesicle” (instant claim 1) “a cell repair-promoting preparation” (instant claim 12), the extracellular vesicle taught by Ofir is obvious over the structurally complete invention in the claim body for the reasons set forth above and is therefore capable of meeting the intended use recited in the preambles and meets instant claims ((see MPEP 2111.02) See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997). Furthermore, Ofir teaches the extracellular vesicles can be used in methods of treatment (para. [0076]; Examples 6-10) and therefore the vesicles would fall under the broadest reasonable interpretation of “cell repair-promoting” as claimed.
Regarding claims 1 and 12, concerning the limitation of “formed by silicate-induced secretion” (instant claim 1) and “formed by silicate-induced” (instant claim 12), these recite product-by process limitations. Applicant is reminded that product-by process claims are not limited by the manipulation of the recited steps, only the structure implied by the steps. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the 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.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (see MPEP 2113). In the instant case, for the reasons set forth above, the extracellular vesicle of instant claims is obvious over the extracellular vesicle of Ofir and therefore the claim is unpatentable.
Furthermore, regarding claims 1 and 12, once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an nonobvious difference between the claimed product and the prior art product. See In re Marosi, 710 F.2d 799, 803, 218 USPQ 289, 292-33 (Fed. Cir. 1983) (see MPEP 2113 (II)).
Regarding claims 2, 4, and 5, further to the discussion of claim 1 above, these claims further limit the product-by process steps of the “silicate-induced secretion” of claim 1. Specifically the product-by process steps of “the stem cells are cultured in a silicate culture medium containing a silicate component” (instant claim 2), “the silicate is a calcium silicate” (instant claim 4), and “the silicate culture medium comprises a culture medium, which comprises a mesenchymal stem cell medium (MSCM) or a Dulbecco' s modified Eagle's medium (DMEM)” (instant claim 5) do not appear to impart an additional structure to the claimed extracellular vesicle and therefore, because the extracellular vesicle of instant claims is obvious over the extracellular vesicle of Ofir for the reasons set forth above, the claim is unpatentable even though the extracellular vesicle of Ofir is made by a different process.
Regarding claim 7, further to the discussion of claim 1 above, as stated above (see claim 1 rejection above), Ofir teaches the extracellular vesicle comprises a membrane surface potential of -38 mV (Table 2) which is very close to the claimed value of -30 mV. As stated above (see claim 1 rejection above), a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close (see Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) and MPEP 2144.05. In the instant case, the taught value of -38 mV is so close to the claimed -30 mV that one of ordinary skill would have expected them to have the same properties.
Regarding claim 9, further to the discussion of claim 1 above, Ofir teaches the exosomes were positive for markers of CD63, CD81, and CD9 (para. [0210]), and Ofir teaches the exosomes in Table 3 were positive for CD63 by ELISA (para. [0212]) and therefore, because the extracellular vesicles are positive for the markers, at least at least 40% of the extracellular vesicles would be expected to express at least one of transmembrane proteins of CD9, CD63, or CD81.
Regarding claim 12, further to the discussion of claim 1 above, concerning the recited limitation of “cells showed significant expression of the miRNA-31 after cultured with the cell repair-promoting preparation then the cells without treatment from the cell repair-promoting preparation, this is interpreted as a conditional limitation. The preparation including extracellular vesicles taught by Ofir makes obvious the structural limitations of the instantly claimed preparation and therefore the preparation including extracellular vesicles taught by Ofir is capable of meeting this conditional limitation should it occur. (see MPEP § 2111.04 (II)).
Regarding claims 15-16, further to the discussion of claim 1 above, these uses are interpreted as intended uses of the claims. For the reasons set forth above, the structural requirements of the extracellular vesicle of instant claims is obvious over the extracellular vesicle of Ofir and therefore is capable the extracellular vesicle of Ofir is capable of meeting the recited intended uses of “for wound repair” (instant claim 15) and “for repairing wounds caused by diabetes which are difficult to treat” (instant clam 16).
Hence, the claimed invention as a whole was prima facie obvious.
Claims 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Ofir et al. (US-20230190822-A1; published 22nd, June 2023 with PCT filed 5th, May, 2021) as applied to claims 1 and 12 above and in further view of Lin et al. (Small. 2021 Mar;17(11):e2007235. Epub 2021 Feb 16.; henceforth “Lin”) as evidenced by Sverdlov (Bioessays. 2012 Oct;34(10):873-5. Epub 2012 Jul 20).
The teachings of Ofir above are incorporated herein in their entirety.
Regarding claims 13-14, while Ofir teaches cell repair-promoting extracellular vesicles and preparations including the vesicles (see claims 1 and 12 rejection above), Ofir is silent to including a hydrogel in the preparation (instant claim 13), and Ofir is silent to a proportion of extracellular vesicles in the hydrogel in the range of between 109-1014 particles/mL (instant claim 14).
Nevertheless, regarding claims 13-14, Lin teaches a hydrogel preparation a cell repair-promoting preparation, comprising a hydrogel carrying an extracellular vesicle at a proportion of 10 µg/mL (Supplementary Materials; Materials and Methods “ADSC-derived-exosome PEG hydrogel formulation”). Lin teaches the preparation yields an injectable preparation that is sufficient to mitigate infection risk while also possessing the antigenic contents and paracrine signaling activity of the ADSC source cells, enabling regeneration of the endometrial microenvironment and offers a convenient, safe, and noninvasive approach for repairing thin endometrium and fertility restoration (abstract).
Therefore, regarding claims 13-14, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the extracellular vesicles of Ofir, and combine the known prior art element of the hydrogel carrying an extracellular vesicle at a proportion of 10 µg/mL of Lin to obtain the predicable result of hydrogel loaded extracellular vesicles. One of ordinary skill would have been motivated to do so as taught by Lin to prepare an injectable preparation to enable regeneration of the endometrial microenvironment offers a convenient, safe, and noninvasive approach for repairing thin endometrium and fertility restoration (abstract). Regarding the reasonable expectation of success, Lin evidenced preparation of a hydrogel preparation a cell repair-promoting preparation, comprising a hydrogel carrying an extracellular vesicle at a proportion of 10 µg/mL (Supplementary Materials; Materials and Methods “ADSC-derived-exosome PEG hydrogel formulation”).
Regarding claim 14, further to the discussion of claim 13 above, while Lin teaches and makes obvious an extracellular vesicle at a proportion of 10 µg/mL for the reasons set forth above, Lin is silent to the proportion of particles/mL in the hydrogel.
Nevertheless, regarding claim 14, Sverdlov evidences 1 µg exosome protein corresponds to 2 x109 exosomes (pg. 874 col. 3rd para.).
Therefore, regarding claim 14, the proportion of 10 µg/mL of exosomes taught and made obvious by Lin above is equivalent to a proportion of 2 x 1010 particles/mL which falls within the claimed range of between 109-1014 particles/mL and thereby makes it obvious.
Notably, regarding claim 14, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. See M.P.E.P. §2144.05.
Finally, regarding claim 14, Additionally, Applicant is reminded that generally, differences in concentration will not support patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical (MPEP 2144.05 II).
Hence, the claimed invention as a whole was prima facie obvious.
Conclusion
No claim is allowable.
Correspondence
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/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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