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 .
Applicant should note that the instant application has been reassigned to a new examiner and now resides in Art Unit 1617.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/04/2016 has been entered.
Claim Status
Claims 1-9 are pending and under current examination.
All rejections not reiterated are withdrawn.
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 1-7 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Shiels et al., (US 2019/0167732 A1, June 06, 2019; of record) in view of Li (TW201021809; publication date: 06/16/2010; citing the English machine translation) and further in view of Lim et al. (US20150024011; publication date: 01/22/2015).
With regard to claims 1 and 2, Shiels discloses methods and compositions based on microvesicles for the treatment of various diseases, disorders and conditions, recognizing that microvesicles contain specific microRNAs which may function as intercellular regulators involved in cell or tissue regeneration, remodeling, reconstruction, reprogramming or transdifferentiation and provide more predictable and effective therapeutic results ([0006]). The invention provides a method of treating a disease, disorder or condition comprising administering to a patient in need of treatment a therapeutically effective amount of microvesicles ([0007]). The term “microvesicle” refers to an exosome ([0060]). Microvesicles are obtained from the milk of a living mammal ([0081]). Examples of diseases, disorders or conditions of the integumentary system that may be treated by the methods and medicaments of the invention include hair loss ([0149]) and autoimmune diseases, such as alopecia ([0127]). The term “treat,” “treatment,” or “treating” refers to any method used to partially or completely inhibit one or more symptoms or features of a particular disease, disorder, and/or condition ([0069]). Suitable microvesicles are isolated or purified by differential ultracentrifugation and/or by precipitation ([0012]).
Shiels discloses a method of treating a disease, disorder or condition comprising administering to a patient in need of treatment a therapeutically effective amount of microvesicles ([0007]), which are exosomes ([0060]) obtained from the milk of a living mammal ([0081]), wherein the treatment includes inhibiting ([0069]) hair loss ([0149]). The prior art is not anticipatory insofar as these combinations must be selected from various lists/locations in the reference.
Moreover, Li teaches that colostrum can rejuvenate follicles (abstract).
Lim teaches that exosomes in general can promote or enhance hair growth.
It would have been obvious, however, to make the combination of elements taught by Shiels, to inhibit hair loss of a subject by administering a therapeutically effective amount for inhibiting hair loss of exosomes isolated from milk, specifically colostrum, wherein the exosomes are not drug carriers. The skilled artisan would have been motivated to focus on these embodiments of Shiels based upon the additional prior art teachings of Li and Lim suggesting efficacy of colostrum (early phase milk) and exosomes in general in hair follicle stimulation/promotion/enhancement of hair growth, and had reasonable expectation of success for the same reason. Moreover, prior art is presumed enabling (see MPEP 2121(I)).
Regarding claims 3-7, as discussed above, Shiels discloses a milk-derived exosome used for hair loss isolated and purified by differential ultracentrifugation and precipitation. Even 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). Similarly, "[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes." Amgen Inc. v. F. Hoffmann-La Roche Ltd., 580 F.3d 1340, 1370 n. 14, 92 USPQ2d 1289, 1312, n. 14 (Fed. Cir. 2009). See also Biogen MA Inc. v. EMD Serono, Inc., 976 F.3d 1326, 1334, 2020 USPQ2d 11129 (Fed. Cir. 2020) ("Biogen is certainly correct that the scope of composition and method of treatment claims is generally subject to distinctly different analyses. But where, as here, the novelty of the method of administration rests wholly on the novelty of the composition administered, which in turn rests on the novelty of the source limitation, the Amgen analysis will necessarily result in the same conclusion on anticipation for both forms of claims."); United Therapeutics Corp. v Liquidia Techs., Inc., 74 F.4th 1360, 1373, 2023 USPQ2d 862 (Fed. Cir. 2023) (the court held that product-by-process claims were properly rejected as "anticipated by a disclosure of the same product irrespective of the processes by which they are made."); and Purdue Pharma v. Epic Pharma, 811 F.3d 1345, 117 USPQ2d 1733 (Fed. Cir. 2016).
In view of the foregoing, the final product disclosed in the instant application holds no patentably distinct structural differences from the final product disclosed by Shiels.
With regard to claim 9, the exosomes are the only active ingredient in the composition.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Shiels et al., (US 2019/0167732 A1, June 06, 2019; of record), Li (TW201021809; publication date: 06/16/2010; citing the English machine translation) and Lim et al. (US20150024011; publication date: 01/22/2015) as applied to claims 1-7 and 9 above, and further in view of Lim (US 2017/0135915 A1, May 18, 2017; of record).
As discussed above, Shiels in view of Li and Lim ‘011 makes obvious the limitations of claim 1 but does not teach wherein the exosomes are formulated in a shampoo formulation.
However, Lim ‘915 discloses the use of an exosome for the preparation of a pharmaceutical composition to promote or enhance would healing or hair growth, or both, in an individual (Abstract). The exosome composition may be applied to skin and hair using any suitable treatment regime ([0075]) and for the treatment or prevention of hair loss and/or the promotion of hair regrowth on the head, a user may wash their hair with a shampoo and then use a conditioner, both the shampoo and the conditioner constituting exosome compositions, the user massaging each product into their scalp before rinsing ([0080]).
As discussed above, Shiels discloses a method of treating and inhibiting hair loss comprising administration of a therapeutically effective amount of exosomes. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have formulated the exosomes used in the method of Shiels in a shampoo since this is a known and effective formulation of exosomes for hair loss as taught by Lim.
Claims 3-7 are rejected under 35 U.S.C. 103 as being unpatentable over Shiels et al., (US 2019/0167732 A1, June 06, 2019; of record), Li (TW201021809; publication date: 06/16/2010; citing the English machine translation) and Lim et al. (US20150024011; publication date: 01/22/2015) as applied to claims 1-7 and 9 above, and further in view of Izumi et al., (EP 3192518 A1, July 19, 2017; Morinaga Milk Industry, cited by applicant on IDS), Bolen et al. (US 2018/0193270 A1, July 12, 2018; of record) and Thery et al. (Journal of Extracellular Vesicles, 2018; of record).
Instant claims 3-7 have been rejected as being obvious over Shiel, Li, and Lim as set forth supra. However, purely arguendo, for the purposes of complete prosecution, and for the purposes of this ground of rejection only, the product by process language of instant claims 3-7 is also obvious as follows:
However, Izumi discloses a method for isolating exosomes from milk, comprising: a centrifugation step of centrifuging raw milk so as to remove fat and cells at 4 degrees Celsius; a step of removing centrifuged fat and cells; a step of adjusting the pH to 4.6 by adding 10% acetic acid and precipitating casein; a step of centrifuging the milk in which casein is precipitated at 4,500 × g and 4°C for 30 minutes, and collecting a supernatant; and a step of filtering the collected supernatant by using a 0.22 µm filter ([0046]), reading on claims 3-4 and 6-7.
Bolen teaches methods of producing exosomes (Abstract) from milk ([0009]) by a first step of centrifugation ([0970] – [0972]), then a first filtration step to further remove fat and cells therefrom ([0973 – 0979]), then a dilution step of adding distilled water to the filtered milk as needed (approximately 10 mL) in order to satisfy manufacturer instructions for properly filled/balanced tubes ([0980]), reading on claim 3.
Thery teaches that for the separation of extracellular vesicles (i.e. exosomes), there is no single optimal separation method, so choose based on the downstream applications and scientific question (Table 1, page 13). Thery et al. teaches the k factor can be determined from the rotor type, tube/adapter, and centrifuge speed and must sometimes be adjusted (Table 1, subparagraph a). Thery et al. teaches for filtration techniques; one must take care to remove cells and other large membranous structures prior to ultrafiltration and that the pore size of the matrix should be taken into account (Table 1 subparagraph b). Thery et al., teaches that time and temperature are also factors that may require adjustment during the exosome separation process (Table 1, Examples for classical technique). A person of ordinary skill in the art, with a reasonable expectation of success, would have been able to adjust the k factor and time of the first centrifugation step to encompass 4,000 to 6,000 x g for 20 to 40 minutes as recited in claim 4, the desired mesh size of the strainer to 20 to 60 µm or 30 to 50 µm as recited in claims 3 and 5, an equal amount of distilled water added to the filtered milk or goat milk as recited in claim 3, and the temperature to room temperature as recited in claim 7 in the instant application with repeated experimentation and a reasonable expectation of success based on the teachings of Thery.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the exosome preparation processes of Izumi and Bolen to prepare the exosomes taught by Shiel motivated by the desire to optimize the separation process according to the downstream application of the exosomes (Thery, Table 1) and to adjust the volume of liquid in the tubes in order to satisfy manufacturer instructions for properly filled/balanced tubes (Bolen, ([0980]).
Response to Arguments
Applicant's arguments filed 06/04/2026 have been fully considered but they are not persuasive.
On pages 4-8, Applicant argues that Shiels discloses many conditions that may be treated and many sources of exosome. Applicant cites the examples of Shiels as not providing direction to select milk exosomes or treat hair growth as they are directed to different exosome sources and different conditions. Applicant argues that one having ordinary skill in the art would not have had reasonable expectation of success because microvesicles obtained from different sources have different concentrations and types of internal components, citing Hamzah and Sanch-Albero. Applicant argues that one having ordinary skill in the art would only arrive at the claimed invention using Applicant’s disclosure as a roadmap, and that the office has used improper hindsight to reconstruct the instant claims.
Applicant’s arguments that Shiels does not provide sufficient direction or expectation of success have been addressed by the new grounds of rejection citing Li and Lim to establish that colostrum and exosomes in general were recognized to promote hair growth. Moreover, simply because the prior art "discloses a multitude of effective combinations does not render any particular formulation less obvious." Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989). "[P]icking and choosing may be entirely proper in the making of a 103, obviousness rejection." In re Arkley, 455 F.2d 586, 587 (CCPA 1972). Furthermore, it is noted that Applicants do not identify secondary consideration demonstrating criticality or anything unexpected about the combination of two known prior art pharmaceutical agents. Conclusive proof of efficacy is not required to show a reasonable expectation of success, and obviousness does not require absolute predictability, but at least some degree of predictability is required. See MPEP 2143.02(I) and (II). Finally, in response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
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 1-9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 14, 21, 23, 24, 26, 28, 30, 31, 33, 35, 37, and 38 of co-pending Application No. 17780391;
claims 1-3, 5, 6, and 9-20 of co-pending Application No. 18/133,886; and
claims 1, 3-9 of co-pending Application No. 18133918
in view of Shiels et al., (US 2019/0167732 A1, June 06, 2019) (hereinafter Shiels), Li (TW201021809; publication date: 06/16/2010; citing the English machine translation) and further in view of Lim et al. (US20150024011; publication date: 01/22/2015).
Co-pending application claims 14, 26, and 33 of the ‘391 application, claim 1 of the ‘886 application, and claim 1 of the ‘918 application teach a method comprising administering a therapeutically effective amount of exosomes isolated from milk or goat milk to the skin of the subject but do not teach a method of preventing or treating hair loss of a subject, as recited in instant claim 1.
Shiels discloses a method of treating a disease, disorder or condition comprising administering to a patient in need of treatment a therapeutically effective amount of microvesicles ([0007]), which are exosomes ([0060]) obtained from the milk of a living mammal ([0081]), wherein the treatment includes inhibiting ([0069]) hair loss ([0149]). Moreover, Li teaches that colostrum can rejuvenate follicles (abstract). Lim teaches that exosomes in general can promote or enhance hair growth.
It would have been obvious to one of ordinary skill in the art to topically administer exosomes derived from milk for the intended use of inhibiting hair loss of a subject, with a reasonable expectation of success according to the teachings of Shiels, Li, and Lim since these references together teach that milk exosomes are effective for inhibiting hair loss.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 06/04/2026 have been fully considered but they are not persuasive.
On page 8, Applicant argues that the Office relies on Shields to bridge the gap between the pending claims and the cited claims and the rejections should be withdrawn for the same reasons presented in traversal of the obviousness rejection.
This is not persuasive for the same reasons set forth above in the Response to Arguments section following the rejection of the claims under 35 USC 103.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE PEEBLES whose telephone number is (571)272-6247. The examiner can normally be reached Monday through Friday: 9 am to 3 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHERINE PEEBLES/ Primary Examiner, Art Unit 1617
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