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 14-15, 21, 23-24, 26-28, 30-31, 33-35, and 37-38 are rejected.
No claims are allowable.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/14/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Maintained Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 14-15, 21, 23-24, 26-28, 30-31, 33-35, and 37-38 are rejected under 35 U.S.C. 103 as being unpatentable over Weon et al., (KR 2019/0045829 A, May 03, 2019) (hereinafter Weon) in view of Gupta et al., (US 2018/0185285 A1, July 05, 2018) (hereinafter Gupta).
Weon teaches a therapeutic method for enhancing transdermal penetration of exosomes ([0016]). The method comprises the steps of topically applying a composition containing exosomes as an active ingredient to the skin of a mammal ([0018]). The term "exosomes" refers to vesicles measuring tens to hundreds of nanometers (preferably approximately 30 to 200 nm) in size and contain proteins, nucleic acids (mRNA, miRNA, etc.) ([0019]) and means all vesicles having a nano-sized vesicle structure secreted from various cells of animals released into the extracellular space ([0021]). Various exosomes can be used as long as they are applicable to the skin and do not cause adverse effects on the human body ([0022]). The method is also used for treating skin disease ([0038]). Skin disease treatment means removing, alleviating or improving pigmented skin lesions, and alleviating, improving or restoring to normal of autoimmune progesterone dermatitis and neurogenic scratch wounds ([0025]). The method is also used for improving the condition of the skin, which can include skin regeneration, wrinkle removal or improvement, whitening ([0037]). In Example 6, exosomes were applied to pig skin at a proper concentration of 1 × 10 5 to 1 × 10 9 particles / mL, demonstrating that the method helps transdermal permeation of exosomes to pig skin ([0075]).
Weon differs from the instant claims insofar as not disclosing exosomes isolated from milk.
However, Gupta discloses exosomes isolated from both bovine milk and colostrum, ranging from 30-100 nm, which can be loaded with a variety of hydrophilic and lipophilic compounds, but exosomes per se (in the absence of therapeutic agent) from both milk and colostrum showed significant cancer cell killing activity ([0134]). The milk-derived exosomes are used in pharmaceutical compositions acceptable in humans and for therapeutic delivery to a subject ([0082]). The composition may be used in transdermal delivery ([0093]). Colostrum-derived exosomes can serve as effective immune booster ([0130]). Microvesicle is used interchangeably with the exosome ([0070]). The exosomes are isolated by a series of sequential centrifugations comprising a first centrifugation at 20,000×g at 4° C. for 30 min, a second centrifugation at 100,000×g at 4° C. for 60 min, and a third centrifugation at 120,000×g at 4° C. for 90 min and passing through a 0.22 μm filter to remove any coagulated particles ([0075]).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. Weon discloses wherein the transdermal composition of the method comprises various exosomes. Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated exosomes isolated from colostrum into the composition of Weon since they are known and effective exosomes suitable for transdermal delivery as taught by Gupta.
Regarding claim 14 reciting accelerating regeneration of wounded skin, Weon teaches that the exosomes are applied to skin and are used in the treatment of skin diseases to improve or restore normal state of a nervous scraping wound, further to improve the condition of the skin through skin regeneration. Neither the claims nor the specification provides a baseline as to what qualifies as “acceleration of wounded skin regeneration”. Therefore, because the application of the composition comprising exosomes as taught by Weon helps with wounded skin restoration and regeneration, it is understood that application of the composition accelerates wounded skin regeneration when compared to no application at all, thus meeting the limitation of claim 14.
Regarding claims 21, 23-24, 28, 30-31, 35, and 37-38, Gupta discloses that the milk-derived exosomes are isolated through a series of steps including centrifugation and filtration. "[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. Since the final product disclosed in the instant application holds no patentably distinct structural differences from the final product disclosed by Gupta, the claim is unpatentable.
Response to Applicant’s Arguments
Applicant argues that nothing in either of Gupta or Weon (Lee) indicates that exosomes isolated from milk have a recognized suitability for use in a method as claimed. Nor do Gupta or Lee provide any teaching, suggestion, motivation, or guidance to utilize exosomes isolated from milk (wherein the exosomes are not drug carriers) in a method as claimed with a reasonable expectation of success because Weon expressly states that the term exosome preferably refers to exosomes excreted by stem cells.
Applicant’s arguments have been fully considered and are found to be persuasive. A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art. See MPEP 2123. As discussed above, Weon discloses a method of restoring skin damaged by scratch wounds, and skin regeneration, wrinkle removal or improvement, and whitening through application of exosomes and teaches that the term exosomes means all vesicles having a nano-sized vesicle structure secreted from various cells of animals released into the extracellular space ([0021]). Thus, various exosomes can be used as long as they are applicable to the skin and do not cause adverse effects on the human body. Gupta teaches that exosomes per se (in the absence of therapeutic agent) isolated from colostrum are suitable for transdermal delivery on human skin. Therefore, since Weon does not limit the types of suitable exosomes to only exosomes secreted by stem cells, one of ordinary skill in the art would have used the exosomes isolated from colostrum disclosed by Gupta in the method of Weon since they are safe and effective for transdermal delivery on human skin. One would have a reasonable expectation of success since Gupta teaches that exosomes isolated from colostrum are safe and effective for treatment of human skin and it is widely known in the art that colostrum is secreted from animal cells.
Further, as stated above, the prior art is evaluated for all that it reasonably suggests, and additionally, it is not limited to preferred embodiments. Although the Examples disclosed by Weon are directed to exosomes excreted by stem cells, as discussed above, Weon also teaches that the term exosomes means all vesicles having a nano-sized vesicle structure secreted from various cells of animals released into the extracellular space. Thus, one of ordinary skill in the art would have expected that any exosome secreted from an animal cell would be suitable for use in the method of Weon.
Applicant argues that Gupta does not teach the use of exosomes isolated from milk as an active agent for skin repair or cosmetic improvement, or provides a reasonable expectation of success for using exosomes isolated from milk that are not drug carrier in methods of accelerating regeneration of wounded skin, reducing wrinkles, or whitening skin.
Applicant’s arguments have been fully considered and are found to be persuasive. Weon teaches that various exosomes may be used in the disclosed skin treatment method and Gupta teaches that exosomes isolated from colostrum (i.e., milk) are safe and effective for treatment of human skin. Thus, as discussed above, it would have been obvious to one of ordinary skill in the art to have used exosomes isolated from colostrum in the method of Weon with a reasonable expectation of success.
Applicant argues that exosomes isolated from milk showed significantly superior efficacy as compared to exosome from other sources, such as HaCat (human keratinocytes)-derived exosomes and serum-derived exosomes, citing FIG. 16 and Fig. 19 of the instant application.
Applicant’s arguments have been fully considered and are found to be persuasive. The results do not appear to be unexpected. The results of FIG. 16 indicate that wound healing was accelerated during treatment with colostrum and commercial milk exosomes compared to serum derived exosomes. FIG. 19 indicates a reduction in melanin pigment production during treatment with colostrum and commercial milk exosomes compared to melanoma cell derived exosomes. However, as evidenced by Schuh et al., (Exosomes on the border of species and kingdom intercommunication, August 2019) (hereinafter Schuh), exosomes isolated from breast milk promote intestinal epithelial cell growth and epithelial–mesenchymal transition and influence immune responses but exosomes isolated from blood serum and malignant effusions are used as biomarkers and for proteomic characterization, respectively (Table 1, page 83). Accordingly, the evidentiary teachings of Schuh indicate that exosomes isolated from breast milk (i.e., colostrum and commercial milk) are used clinically and have a therapeutic effect, as opposed to serum and malignantly derived exosomes being used diagnostically rather than therapeutically. Thus, it would not be unexpected that treatment with the colostrum and commercial milk derived exosomes of the instant invention would result in accelerated wound healing and reduced melanin production when compared to serum and malignant cell exosomes since these are therapeutic results, and breast milk derived exosomes are known to produce therapeutic results while serum and malignantly derived exosomes are known to be used for diagnostic purposes, as taught by Schuh. As such, the superior results shown by the instantly claimed invention would not be unexpected to one of ordinary skill in the art.
For the foregoing reasons, the rejection is maintained.
Maintained Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 14-15, 21, 23-24, 26-28, 30-31, 33-35, and 37-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of copending Application No. 18/133,886 in view of Weon et al., (KR 2019/0045829 A, May 03, 2019) (hereinafter Weon).
The copending claims are directed to a method of enhancing immunity of a subject, comprising administering a therapeutically effective amount of exosomes isolated from cow milk or goat milk to the subject, wherein the therapeutically effective amount of exosomes is effective to increase expression of CD54, CXCL1, CCL3, CCL5, and TNF-a in the subject, wherein the exosomes are not drug carriers, but does not teach a method of accelerating regeneration of wounded skin, reducing wrinkles, or whitening skin of a subject in need thereof.
However, Weon teaches a cosmetic method for regulating the condition of mammalian skin other than for therapeutic use or a method for treating skin disease by using the method for enhancing transdermal penetration of exosomes ([0015]). The method comprises the steps of topically applying a composition containing exosomes as an active ingredient to the skin of a mammal ([0018]). The term "exosomes" refers to vesicles measuring tens to hundreds of nanometers (preferably approximately 30 to 200 nm) in size and contain proteins, nucleic acids (mRNA, miRNA, etc.) ([0019]) and means all vesicles having a nano-sized vesicle structure secreted from various cells of animals released into the extracellular space and having a composition similar to exosomes (e.g., exosome-like vesicles) (0021]). Various exosomes can be used as long as they are applicable to the skin and do not cause adverse effects on the human body ([0022]). Skin disease treatment means removing, alleviating or improving pigmented skin lesions, and alleviating, improving or restoring to normal of autoimmune progesterone dermatitis and neurogenic scratch wounds ([0025]). Regulating the condition of the skin means improving the condition of the skin, which can include skin regeneration, wrinkle removal or improvement, whitening ([0037]). Accordingly, it would have been obvious to one of ordinary skill in the art to have used the exosomes of the copending claims in a method of accelerating regeneration of wounded skin, reducing wrinkles, or whitening skin of a subject in need thereof, since exosomes are used as an active ingredient that regenerate skin, including wounded skin, remove wrinkles, and whiten skin, as taught by Weon.
This is a provisional nonstatutory double patenting rejection.
Claims 14-15, 21, 23-24, 26-28, 30-31, 33-35, and 37-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of copending Application No. 18/133,918 in view of Weon et al., (KR 2019/0045829 A, May 03, 2019) (hereinafter Weon).
The copending claims are directed to a method of inhibiting UV-induced oxidative damage of cells, comprising treating the cells with an effective amount for inhibiting UV-induced oxidative damage of exosomes isolated from cow milk or goat milk, wherein the exosomes are not drug carriers, but does not teach a method of accelerating regeneration of wounded skin, reducing wrinkles, or whitening skin of a subject in need thereof.
However, Weon teaches a cosmetic method for regulating the condition of mammalian skin other than for therapeutic use or a method for treating skin disease by using the method for enhancing transdermal penetration of exosomes ([0015]). The method comprises the steps of topically applying a composition containing exosomes as an active ingredient to the skin of a mammal ([0018]). The term "exosomes" refers to vesicles measuring tens to hundreds of nanometers (preferably approximately 30 to 200 nm) in size and contain proteins, nucleic acids (mRNA, miRNA, etc.) ([0019]) and means all vesicles having a nano-sized vesicle structure secreted from various cells of animals released into the extracellular space and having a composition similar to exosomes (e.g., exosome-like vesicles) (0021]). Various exosomes can be used as long as they are applicable to the skin and do not cause adverse effects on the human body ([0022]). Skin disease treatment means removing, alleviating or improving pigmented skin lesions, and alleviating, improving or restoring to normal of autoimmune progesterone dermatitis and neurogenic scratch wounds ([0025]). Regulating the condition of the skin means improving the condition of the skin, which can include skin regeneration, wrinkle removal or improvement, whitening ([0037]). Accordingly, it would have been obvious to one of ordinary skill in the art to use the exosomes of the copending claims in a method of accelerating regeneration of wounded skin, reducing wrinkles, or whitening skin of a subject in need thereof since exosomes are used as an active ingredient that regenerate skin, including wounded skin, remove wrinkles, and whiten skin, as taught by Weon.
This is a provisional nonstatutory double patenting rejection.
Claims 14-15, 21, 23-24, 26-28, 30-31, 33-35, and 37-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of copending Application No. 18/133,901 in view of Weon et al., (KR 2019/0045829 A, May 03, 2019) (hereinafter Weon).
The copending claims are directed to a method of inhibiting or treating hair loss of a subject, comprising administering to the subject a therapeutically effective amount for inhibiting or treating hair loss of exosomes isolated from milk, wherein the exosomes are not drug carriers, but does not teach a method of accelerating regeneration of wounded skin, reducing wrinkles, or whitening skin of a subject in need thereof.
However, Weon teaches a cosmetic method for regulating the condition of mammalian skin other than for therapeutic use or a method for treating skin disease by using the method for enhancing transdermal penetration of exosomes ([0015]). The method comprises the steps of topically applying a composition containing exosomes as an active ingredient to the skin of a mammal ([0018]). The term "exosomes" refers to vesicles measuring tens to hundreds of nanometers (preferably approximately 30 to 200 nm) in size and contain proteins, nucleic acids (mRNA, miRNA, etc.) ([0019]) and means all vesicles having a nano-sized vesicle structure secreted from various cells of animals released into the extracellular space and having a composition similar to exosomes (e.g., exosome-like vesicles) (0021]). Various exosomes can be used as long as they are applicable to the skin and do not cause adverse effects on the human body ([0022]). Skin disease treatment means removing, alleviating or improving pigmented skin lesions, and alleviating, improving or restoring to normal of autoimmune progesterone dermatitis and neurogenic scratch wounds ([0025]). Regulating the condition of the skin means improving the condition of the skin, which can include skin regeneration, wrinkle removal or improvement, whitening ([0037]). Accordingly, it would have been obvious to one of ordinary skill in the art to use the exosomes of the copending claims in a method of accelerating regeneration of wounded skin, reducing wrinkles, or whitening skin of a subject in need thereof since exosomes are used as an active ingredient that regenerate skin, including wounded skin, remove wrinkles, and whiten skin, as taught by Weon.
This is a provisional nonstatutory double patenting rejection.
Response to Applicant’s Arguments
Applicant argues that the OTDP rejections rely on Weon (Lee) to bridge the gap between the pending claims and the cited claims, however, Lee does not suggest or provide a reasonable expectation of success for using exosomes isolated from milk in a method as claimed.
Applicant’s arguments have been fully considered and are found to be persuasive. The Examiner submits that Applicant’s argument with regards to Weon (Lee) is addressed above and is unpersuasive. Therefore, these rejections are maintained.
Applicant disagrees with the basic premise underlying the OTDP rejections that the claimed methods for accelerating regeneration of wounded skin (claim 14), reducing wrinkles (claim 26), or whitening skin (claim 33), are not patentably distinct from the methods recited in the cited claims.
Applicant’s argument has been fully considered but found not to be persuasive. As discussed above, Weon teaches the use of all exosomes secreted from various cells of animals in methods of accelerating regeneration of wounded skin, reducing wrinkles, and whitening skin and that they are the active ingredient. Thus, it would have been obvious to use the milk exosomes of the copending applications in such methods since they are exosomes secreted by the cells of bovine animals.
For the foregoing reasons, the rejections are maintained.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Samantha J Knight whose telephone number is (571)270-3760. The examiner can normally be reached Monday - Friday 8:30 am to 5:00 pm ET.
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/S.J.K./ Examiner, Art Unit 1614
/TRACY LIU/ Primary Examiner, Art Unit 1614