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 .
This office action is in response to the amendment filed on May 18th, 2026.
The Applicant has added claims 16-22. Claims 8 and 16-22 are pending and are under examination.
Any objections or rejections not reiterated below are hereby withdrawn.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a
prior Office action.
Withdrawal of Objections and Rejections
Applicant’s arguments, filed May 18th, 2026, with respect to the rejection of claim 8 under 35 U.S.C. 112(b) have been fully considered and are persuasive. The applicant has amended claim 8 to recite the materials used in the extraction of bee pollen exosomes, the time and temperature parameters of the extraction, and explicitly recite “to provide an extract”. Therefore, the previous ground of rejection under 35 U.S.C 112(b) has been withdrawn. However, upon further consideration, a new ground of rejection is made in view of the requirements for compliance with 35 U.S.C. 112(b), as explained below.
Pending Objections and Rejections
Specification
The disclosure is objected to because of the following informalities: the disclosure recites at least the following abbreviations without providing their non-abbreviated forms at their first mention: "FBS", and "MMP-1".
The disclosure is objected to because of the following informalities: the disclosure recites "0.00003% of the bee pollen exosome" in Preparation example 2, but it is not clear whether this value is a weight percent, volume percent or weight/volume percent. Clarification is requested regarding whether "0.00003% of the bee pollen exosome" in Preparation example 2, refers to a weight percent, volume percent or weight/volume percent.
Appropriate correction is required.
The use of the terms DuoSet and Antera 3D, each of which is a trade name or a mark used in commerce, has been noted in this application. Each term should be accompanied by the generic terminology; furthermore, each term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 20 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: the materials used in the washing step and how they are combined or contacted. appears that step iv of claim 16 provides a purified exosome, so it is not clear what is being washed. It is not clear what materials are used to perform the wash.
Claim 21 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 21 disclosure recites "0.00003% of the purified exosome", but it is not clear whether this value is a weight percent, volume percent or weight/volume percent. The specification recites "0.00003% of the bee pollen exosome" in Preparation example 2, but it is not clear whether this value is a weight percent, volume percent or weight/volume percent.
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.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Schuh et al. (Journal of Experimental Biology 2019, 222, jeb208702), abbreviated “Schuh” .
Applicant's arguments filed May 18th, 2026 have been fully considered but they are not persuasive.
Although the extraction of bee pollen is not explicitly recited by Schuh, dissolving. Although Schuh recites combining bee pollen with particle-free
phosphate-buffered saline (pf-PBS) instead of purified water, it would have been obvious to one of skill in the art to substitute purified water for pf-PBS. Both purified water and pf-PBS are known in the art as polar solvents able to dissolve polar molecular structures. One of skill in the art could have substituted pf-PBS with purified water with the predictable effect of dissolving exosomes by dissolving the solvent-exposed polar head groups of the phospholipids comprising the exosome membrane. Therefore, it would be obvious to one of skill in the art to substitute pf-PBS with purified water as an extraction solvent for preparing an exosome.
Although Schuh does not explicitly recite an extraction temperature range from 4 °C to 25 °C and an extraction time of 24 hours to 72 hours, these parameters are obvious to one of skill in the art over routine optimization. One of skill in the art could use a thermometer to measure temperature and a timer to measure time. One of skill in the art could use a refrigerator to manipulate the temperature of an extraction mixture between 4 °C and 25 °C. One of skill in the art could test the efficiency of different exosome extraction procedures, varying according to time and/or temperature, by analyzing the resulting extract for exosome content by comparing the mass of isolated exosome material (measured using an analytical balance). Therefore, the extraction time and temperature parameters recited in claim 8 are obvious to one of skill in the art over routine optimization.
Schuh is relied upon for the reasons discussed above. If not expressly taught thereby, based upon the overall beneficial teachings provided by the references with respect to providing the method of preparing a bee pollen exosome, the adjustments of particular conventional working conditions (e.g., the selection from among known components and determining one or more suitable ranges (amounts, proportions, ratios thereof) in which to provide the method of extraction and isolation of a bee pollen exosome), is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan.
From the teachings of Schuh, the invention as a whole, drawn to method of preparing a bee pollen exosome as described in Claim 8, would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, and one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Please note, since the Office does not have the facilities for examining and comparing Applicants’ methods with the methods (including compositions thereof) of the prior art, the burden is on applicant to show a novel or unobvious difference between the claimed methods and the methods of the prior art (and compositions thereof). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980), and “as a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
Claims 16, 17, 21, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Schuh et al. (Journal of Experimental Biology 2019, 222, jeb208702), abbreviated “Schuh”, and further in view of Kim (KR 20220150088 A).
Claim 16 recites “A method of preparing a bee pollen exosome, comprising: (i) grinding a composition comprising bee pollen; (ii) extracting the bee pollen with purified water at a temperature from 4° C to 25° C for 24 hours to 72 hours to provide an extract; (iii) removing a precipitate from the extract by centrifugation then taking a supernatant; (iv) filtering the supernatant to provide a purified exosome; (v) adding butylene glycol, 1,2-hexanediol, ethylhexylglycerin, and purified water to the purified exosome to provide a mixture, followed by agitation; and (vi) filtering the mixture to provide a bee pollen exosome”. Claim 17 recites “The method according to claim 16, wherein the filtering in (iv) is performed using a filter having a pore size of 0.2 pm to 5.0 pm”. Claim 21 recites “The method according to claim 16, wherein in step (v), 10% of butylene glycol, 2% of 1,2-hexanediol, 0.05% of ethylhexylglycerin, and purified water (to 100%), based on wt %, is added to 0.00003% of the purified exosome from (iv)”. Claim 22 recites “The method according to claim 16, wherein in (vi), a density of the bee pollen exosome is 1.004 g/mL”.
Schuh recites the following procedure for the isolation of exosomes from bee products: “Honey and royal jelly (Apicola del Alba, Chile) were diluted 1:20 in particle-free phosphate-buffered saline (pf-PBS). Bee pollen was dissolved 1:40 (w/v) in pf-PBS. All samples were centrifuged at 500 g, 1500 g and 2500 g for 15 min each and subsequently filtered (0.2 µm). Supernatant was ultra centrifuged twice at 100,000 g for 70 min (Thermo Scientific Sorvall). The resulting pellet containing exosomes was resuspended in pf-PBS and stored at −80°C until experimentation (scheme depicted in Fig. S1)” (Schuh et al., Materials and Methods, Isolation of exosomes from bee products; instant claim 8). The method recited by Schuh et al. is explicitly recited as isolating exosomes from bee products in the first subheading under Materials and Methods, and provides a pellet containing exosomes. The instantly claimed procedure in claim 16, and dependent claims 17-19, 21, and 22 comprises analogous steps but exclude centrifuging the supernatant as recited in the reference. However, in both the instant claims and Schuh, the exosome is sourced from this supernatant.
Although Schuh does not explicitly recite grinding a composition comprising bee pollen (instant claim 16, step i), it is within the knowledge of one of skill in the art that grinding a material increases its surface area to volume ratio, providing more surface area for solvent to contact, improving the efficiency of dissolving components from the composition into the solvent(the efficiency of extraction). Therefore, grinding the composition comprising bee pollen before extracting the bee pollen, or combining the bee pollen with a solvent to dissolve the bee pollen exosome therefrom, would be obvious to one of skill in the art (instant claim 16).
Although Schuh does not explicitly recite that the centrifugation of bee pollen samples removes a precipitate, it is within the knowledge of skill in the art that centrifugation is a method of separating components of a mixture, including liquid phases from solid phases (instant claim 16, step iii). Furthermore, Schuh explicitly recites a supernatant directly after the first centrifugation step, implying that there was pellet left, distinct from the supernatant. The separation of supernatant from pellet implies the removal of a precipitate from the liquid phase of the mixture. Therefore, one of skill in the art would have a reasonable expectation of success at performing the first centrifugation step taught by Schuh, above, resulting in the removal of a precipitate (instant claim 16, step iii).
Although Schuh des not explicitly recite filtering the supernatant after the first centrifugation step (claim 16, step iv), Schuh recites the samples being centrifuged and subsequently filtered, and does not exclude filtering the supernatant or the pellet resulting from the first centrifugation (claim 16, step iii). The filtering threshold recited by Schuh above is 0.2 μM (instant claim 17).
Although the extraction of bee pollen is not explicitly recited by Schuh, dissolving. Although Schuh recites combining bee pollen with particle-free
phosphate-buffered saline (pf-PBS) instead of purified water, it would have been obvious to one of skill in the art to substitute purified water for pf-PBS. Both purified water and pf-PBS are known in the art as polar solvents able to dissolve polar molecular structures. One of skill in the art could have substituted pf-PBS with purified water with the predictable effect of dissolving exosomes by dissolving the solvent-exposed polar head groups of the phospholipids comprising the exosome membrane. Therefore, it would be obvious to one of skill in the art to substitute pf-PBS with purified water as an extraction solvent for preparing an exosome (instant claim 16).
Instant claims 16 (step v) and 21 are distinguished from Schuh in that Schuh does not explicitly recite adding butylene glycol, 1,2-hexanediol, ethylhexylglycerin, and purified water to the purified exosome. However, diluting the exosome with a solvent is obvious over routine optimization to one of skill in the art to manipulate the dose of the exosome administered per unit volume. One of skill in the art could then observe the biological effects of the composition by photographing skin to which the composition is repeatedly applied, and an untreated (negative control) area of skin for comparison. One of skill in the art could also perform the antibacterial, biofilm inhibition, exosome internalization, and/or cellular migration assay recited by Schuh (Materials and Methods), to compare the biological effects of different compositions. Purified water would be obvious to one of skill in the art use to dilute the exosome, because water is broadly recognized as a bio-compatible substance. Butylene glycol, 1,2-hexanediol, and ethylhexylglycerin, would be obvious to one of skill in the art to add as preservatives to inhibit the growth of microorganisms in the mixture comprising the exosome (Kim, machine translation page 6 of 11, lines 24-29 from the top; instant claim 16, step v; instant claim 21). It is within the knowledge and skill of one of skill in the art to agitate the mixture to evenly distribute the mixture components, to create a substance of uniform composition, making the biological activity of any given sample of that substance predictable (instant claim 16, step v). It would further be obvious to filter the mixture, to remove debris and microbial cells that could chemically alter the mixture over time (claim 16 step vi).
Although Schuh does not explicitly recite an extraction temperature range from 4 °C to 25 °C and an extraction time of 24 hours to 72 hours (instant claim 16, step ii), these parameters are obvious to one of skill in the art over routine optimization. One of skill in the art could use a thermometer to measure temperature and a timer to measure time. One of skill in the art could use a refrigerator to manipulate the temperature of an extraction mixture between 4 °C and 25 °C. One of skill in the art could test the efficiency of different exosome extraction procedures, varying according to time and/or temperature, by analyzing the resulting extract for exosome content by comparing the mass of isolated exosome material (measured using an analytical balance). Therefore, the extraction time and temperature parameters recited in instant claim 16, step ii are obvious to one of skill in the art over routine optimization.
Instant claims 21 and 22 are distinguished from the cited references in that they recite “10% of butylene glycol, 2% of 1,2-hexanediol, 0.05% of ethylhexylglycerin, and purified water (to 100%), based on wt % is added to 0.00003% of the purified exosome from (iv)” (instant claim 21) and “a density of the bee pollen exosome is 1.004 g/mL” (instant claim 22). However, one of skill in the art can measure and adjust weight percents of components of a composition using scale instrument, and make mass and volume measurements to calculate the density of a composition. One of skill in the art could use volumetric glassware to make volume measurements and a scale to measure weight (if either volume/volume or weight/volume percent is applicable to “0.00003% of the purified exosome from (iv)” (instant claim 21)). One of skill in the art could adjust the density of the exosome composition by diluting the exosome in water (having a density of 1 g/mL), with a reasonable expectation of success at producing a composition with a density of 1.004 g/mL. One of skill in the art could then observe the biological effects of compositions varying according to the parameters recited above by photographing skin to which the composition is repeatedly applied, and an untreated (negative control) area of skin for comparison. One of skill in the art could also perform the antibacterial, biofilm inhibition, exosome internalization, and/or cellular migration assay recited by Schuh (Materials and Methods), to compare the biological effects of different compositions. Therefore, the parameters recited in instant claims 21 and 22 are obvious to one of skill in the art over routine optimization.
Schuh and Kim are relied upon for the reasons discussed above. If not expressly taught thereby, based upon the overall beneficial teachings provided by the references with respect to providing the steps of preparing a bee pollen exosome, the adjustments of particular conventional working conditions (e.g., the selection from among known components and determining one or more suitable ranges (amounts, proportions, ratios thereof) in which to provide the method of preparing a bee pollen exosome), is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan.
From the teachings of Schuh in view of Kim, the invention as a whole, drawn to a method of preparing a bee pollen exosome as described in Claims 16, 17, 21, and 22, would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, and one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Please note, since the Office does not have the facilities for examining and comparing Applicants’ methods with the methods (including compositions thereof) of the prior art, the burden is on applicant to show a novel or unobvious difference between the claimed methods and the methods of the prior art (and compositions thereof). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980), and “as a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
Claims 16-19, 21, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Schuh et al. (Journal of Experimental Biology 2019, 222, jeb2087022), abbreviated Schuh; and further in view of Kim (KR 20220150088 A), as applied to claims 16, 17, 21, and 22 above, and further in view of Kelwick (US 20220356269 A1); Cho et al. (US 20220364051 A1), abbreviated "Cho"; and Schuh (Journal of Experimental Biology 2019, 222, jeb2087022).
Claim 18 recites “The method according to claim 17, wherein the filtering in (iv) is further performed using a tangential flow filtration device (TFF device)”. Claim 19 recites “The method according to claim 18, wherein the filtering using a TFF device is performed using a 100 kDa filter”.
Claims 16, 17, 21, and 22 and the teachings of the cited references Schuh and Kim are of record above.
Although Schuh teaches a filtration step (instant claims 16, step iv), Schuh does not teach that this filtering step is performed using a tangential flow filtration device (TFF device) (instant claims 18 and 19). However, Kelwick recites tangential flow filtration as an exosome isolation method (paragraph [0005], implying that TFF is applicable to preparing an exosome, and would yield a predictable result of removing impurities above the filtration threshold from the exosome-containing composition.
Although Schuh and Kim do not explicitly recite “using a TFF device is performed using a 100 kDa filter” (instant claim 19). However, Cho recites isolating exosomes from different plant types using tangential flow filtration, where the filter cutoff value is 100 to 500 kDa (aloe peel, paragraphs [0045]-[0048]; garlic, paragraph [0055]). In an exosome purification process as recited in claim 16 step iv there is a need to remove impurities, Cho provides a finite range of filter cutoffs of 100-500 kDa for isolating plant exosomes, and there is a reasonable expectation of pursuing these filtration cutoffs using TFF as recited by Cho. Therefore, it would have at least been obvious to try using a TFF filter cutoff of 100kDa for the purification of a bee pollen exosome (instant claim 19). Based on the teaching of Cho, one of skill in the art could vary the filter cutoff for TFF between 100 and 500 kDa. One of skill in the art could then observe the biological effects of compositions varying according to the TFF cutoff by photographing skin to which the composition is repeatedly applied, and an untreated (negative control) area of skin for comparison. One of skill in the art could also perform the antibacterial, biofilm inhibition, exosome internalization, and/or cellular migration assay recited by Schuh (Materials and Methods), to compare the biological effects of different compositions. Therefore, the TFF cutoff of 100 kDa would also be obvious to one of skill in the art over routine optimization (instant claim 19).
Schuh, Kim, Kelwick, and Cho are relied upon for the reasons discussed above. If not expressly taught thereby, based upon the overall beneficial teachings provided by the references with respect to providing the steps of preparing a bee pollen exosome, the adjustments of particular conventional working conditions (e.g., the selection from among known components and determining one or more suitable ranges (amounts, proportions, ratios thereof) in which to provide the method of preparing a bee pollen exosome), is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan.
From the teachings of Schuh in view of Kim, Kelwick, and Cho, the invention as a whole, drawn to a method of preparing a bee pollen exosome as described in Claims 16-19, 21, and 22, would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, and one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Please note, since the Office does not have the facilities for examining and comparing Applicants’ methods with the methods (including compositions thereof) of the prior art, the burden is on applicant to show a novel or unobvious difference between the claimed methods and the methods of the prior art (and compositions thereof). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980), and “as a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 Robert F Spaine whose telephone number is (571)272-9099. The examiner can normally be reached 8:00 AM - 4:00 PM United States Eastern Time, Monday-Friday.
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/R.F.S./Examiner, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
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