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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/04/2025 has been entered.
Claim 11 has been amended. No claims are newly added or newly canceled.
Claims 1-12, 15, 17-20 and 24-25 are currently pending.
Claims 1-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/31/2024.
Claims 11-12, 15, 17-20, and 24-25 have been examined on their merits.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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.
Claims 11-12, 15, 17-20, and 24-25 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.
Applicant has amended claim 11 by incorporating the limitations of canceled claims 13, 14, 16, and 21-23 in a previous amendment. This combination of embodiments has caused the scope of amended claim 11 to be indefinite as it includes multiple requirements with regard to the administration of an agent and it is unclear how they occur in the same method.
Amended claim 11 now also requires “wherein myopia and corrected eyesight are temporarily improved for an administration period during which the ocular symptom-improving agent is administered to the subject and for three months after the completion of the administration” in lines 11-15 and “wherein the ocular improving agent is administered to the subject one or more times a day for a therapeutically effective period” in lines 19-20.
This combination of limitations appears to be an attempt to combine several embodiments into one method and renders the claim confusing as to what duration of administration period is actually required.
For examination purposes “the administration period” is interpreted to refer to a therapeutically effective administration period for the improvement of myopia and corrected eyesight of myopia with nothing more than the agent of a culture supernatant of dental pulp stem cells required.
The preamble of claim 11 has been amended to “a method for improving myopia and corrected eyesight in a subject in need thereof”, however dependent claims refer to the old preamble of “The method for improving an ocular symptom”.
Dependent claim 18 still refers to subjects in the alternative to myopia and thus renders this claim indefinite as well as it appears to indicate subjects with myopia as optional and doesn’t even include subjects with corrected eyesight due to myopia as required by claim 11.
Because claims 12, 15, 17-20, and 24-25 depend from indefinite claim 11 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112, second paragraph.
Appropriate correction is required.
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.
Claim(s) 11-12, 15, 17-20, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Kobayashi et al (WO 2020/130038-from IDS filed 12/13/2023, using machine translation) in view of Prockop et al (WO 2011/139357) and as evidenced by Tomarev et al (US 2019/0224242).
Regarding claims 11, 15, 17, 24, Kobayashi disclose methods for administering an effective amount of a composition for regenerative therapy wherein the composition contains cytokines contained in a stem cell culture supernatant obtained from culturing dental pulp-derived stem cells (abstract, pages 3-5). The regenerative therapy is disclosed as being used to treat ocular symptoms such as myopia, presbyopia, and dry eye (all include treatment of blurred vision) (page 9, page 14). Patients with myopia are deemed to also require eye glasses for correction of their eyesight as well. Therefore an improvement in myopia is deemed to also improve the corrected eyesight of the subject as well.
Kobayashi is silent with regard to how long the ocular symptom is corrected during which the agent is administered to the subject, however Kobayashi is carrying out the same step of administering the same agent and directed to the treatment of the same subjects of myopia (which requires the correction of the eyesight) and therefore the effect is either inherently present or obtainable through routine optimization and experimentation.
Providing guidance on instances where the method steps of the prior art and instant claims are the same, Ex parte Marhold, 231 USPQ 904, 905 (Bd. Pat. App. & Int. 1986) relying on In re Sussman, 141 F.2d 267, 269-70, 60 USPQ 538, 540-41 (CCPA 1944) states “[T]hat since the steps are the same, the results must inherently be the same unless they are due to conditions not recited in the claims.”
The presence of exosomes in the culture supernatant of dental pulp stem cells is an inherent feature as evidenced by Tomarev (page 11 para 110) and Applicant’s Specification (page 13 para 27).
One of ordinary skill in the art would have had additional motivation to select the eye disorder of myopia from the list of disorders to be treated in the method of Kobayashi because Prockop teach methods of treating anterior ocular conditions, such as myopia, by administering the culture supernatant of mesenchymal stem cells (page 18, page 42 third paragraph). One of ordinary skill in the art would have had a reasonable expectation of success because Prockop indicate that MSCs can be obtained from any source (page 32) and that they secrete therapeutic proteins (page 18, page 40, page 47).
Kobayashi is silent with regard to the number of times or duration of administration of the stem cell culture supernatant (ocular symptom improving agent).
However, Prockop teach that administration of their MSC-derived compositions can vary and include intraocular administration over a period of time (administration period) and can include multiple administrations, including daily dosages (one or more times a day), for a period of time to provide a therapeutic effect (page 49, page 54). Prockop teach that it should be understood that their methods may be carried out in a number of ways and with various modifications and permutations well known in the art (page 40).
Therefore one of ordinary skill in the art would have been motivated to modify the administration of the ocular symptom improving agent in the method of Kobayashi to include daily administrations over the course of a time period found to provide a therapeutic effect for the improvement of myopia because Prockop teach and suggest that multiple administrations, including daily dosages (one or more times a day), for a period of time to provide a therapeutic effect are suitable and beneficial for treatment methods of these ocular disorders with a MSC culture supernatant. One of ordinary skill in the art would have had a reasonable expectation of success because Prockop indicate that MSCs can be obtained from any source (page 32) and that they secrete therapeutic proteins (page 18, page 40, page 47) and Kobayashi is also using the culture supernatant of a MSC culture for an ocular improving agent.
Kobayashi is silent with regard to what type of eyesight was improved (corrected or uncorrected or the focus distance), however Kobayashi is carrying out the same step of administering the same agent and directed to the treatment of the same subjects of myopia and presbyopia and therefore the effect is either inherently present or obtainable through routine optimization experimentation.
Providing guidance on instances where the method steps of the prior art and instant claims are the same, Ex parte Marhold, 231 USPQ 904, 905 (Bd. Pat. App. & Int. 1986) relying on In re Sussman, 141 F.2d 267, 269-70, 60 USPQ 538, 540-41 (CCPA 1944) states “[T]hat since the steps are the same, the results must inherently be the same unless they are due to conditions not recited in the claims.”
Regarding claims 12 and 19, Kobayashi disclose wherein their culture supernatant is administered to humans and non-human mammals (page 5).
Regarding claim 18, Kobayashi teach that administration types include eye drops (ocular administration) (page 9).
Regarding claim 20, Kobayashi teach wherein the subject may have myopia or presbyopia (page 5) but do not indicate wherein the subject has a cataract or glaucoma.
Therefore the combined teachings of Kobayashi et al and Prockop et al render obvious Applicant’s invention as claimed.
Claim(s) 25 is rejected under 35 U.S.C. 103 as being unpatentable over Kobayashi et al (WO 2020/130038-from IDS filed 12/13/2023, using machine translation) in view of Prockop et al (WO 2011/139357) and as evidenced by Tomarev et al (US 2019/0224242) as applied to claims 11-12, 15, 17-20, and 24 above, and further in view of Tatsuya (JP 2019156742-from IDS filed 12/13/2023, using machine translation).
Regarding claim 25, the combined teachings of Kobayashi and Prockop render obvious the claimed method as described above, but do not specifically mention the use of a culture supernatant of immortalized stem cells of dental pulp derived stem cells.
Tatsuya a method of treating an ocular disorder, such as presbyopia, with a culture supernatant component by culturing mesenchymal stem cells (abstract). Tatsuya teach that not only primary cells but also mesenchymal stem cells established/immortalized by genetic modification or the like can be used (page 2).
One of ordinary skill in the art would have been motivated to use a culture supernatant of immortalized stem cells in the method of Kobayashi because Tatsuya teach that not only primary cells but also mesenchymal stem cells established/immortalized by genetic modification or the like can be used (page 2). One of ordinary skill in the art would have had a reasonable expectation of success because Kobayashi and Tatsuya are both directed to the treatment of ocular disorders with the culture supernatant of mesenchymal stem cells and Prockop indicate that MSCs can be obtained from any source (page 32) and that they secrete therapeutic proteins (page 18, page 40, page 47).
Therefore, the combined teachings of Kobayashi et al, Prockop et al and Tatsuya render obvious Applicant’s invention as claimed.
Response to Arguments
Applicant's arguments filed 03/03/2025 have been fully considered but they are not persuasive.
Applicant asserts that their amendment has overcome the issues under 35 USC 112(b).
This is not found persuasive. As explained above, it is still unclear what administration period is required for the claimed method. Claim 11 still requires therapeutic effects of improving myopia and corrected eyesight with temporary improvement for three months after completion of administration and wherein the agent is administered one or more times a day for a therapeutically effective period. Since there does not appear to be anything specific other than the agent required for these effects to occur (including no special administration requirements connected to these claimed effects disclosed in Applicant’s Specification) the claim has been interpreted as inherently providing the claimed effects when the agent is administered to a subject with myopia and corrected eyesight. If a special dose or administration detail is required for the effect of temporary improvement three months after completion of administration of the agent then these details would need to be recited in the claims for purposes of enablement.
Applicant asserts that the Examiner admits that Kobayashi do not disclose how long the ocular symptom is corrected during which the administration is administered and that Kobayashi do not disclose a method for improving myopia and corrected eyesight. Applicant asserts that Kobayashi do not have all the inherent features of claim 11 in view of the combination of all the claimed limitations regarding therapeutic effects, duration of administration, administration interval, second administration and improving myopia or corrected eyesight.
This is not found persuasive. First, Kobayashi does in fact teach the treatment of myopia with culture supernatant of dental pulp stem cells as described above. Second, while Kobayashi is silent with regard to how long the ocular symptom is corrected during which the agent is administered to the subject, they are carrying out the same step of administering the same agent and directed to the treatment of the same subjects of myopia (which requires the correction of the eyesight) and therefore the effect is either inherently present or obtainable through routine optimization and experimentation. Applicant’s claims do not include any specifics for how administration is to be carried out to achieve the claimed effects and therefore, baring evidence to the contrary, the effects are deemed to be inherently present or achieved through routine experimentation and optimization.
Applicant argues that the reliance on the teaching of Prockop and thus “multiple references” to render the claims obvious cannot be accomplished because an unrecognized property that may be inherent to a single reference cannot be properly applied to a combination of references.
This is not found persuasive. Regarding the issue of inherency, see Persion Pharms. LLC v. Alvogen Malta Operations LTD., 945 F.3d 1184, 1191, 2019 USPQ2d 494084 (Fed. Cir. 2019), where the court stated that a proper finding of inherency does not require that all limitations are taught in a single reference, and that inherency may meet a missing claim limitation when the limitation is "the natural result of the combination of prior art elements." (emphasis in original). The court found that pharmacokinetic limitations of the asserted claims were inherently met by combining prior art references because the limitations were necessarily present in the prior art combination. Id. See also Hospira, Inc. v. Fresenius Kabi USA, LLC, 946 F.3d 1322, 1329-32, 2020 USPQ2d 6227 (Fed. Cir. 2020). (see MPEP 2112 (IV)).
Applicant argues that amended claim 11 is not obtainable by routine optimization. Applicant argues that because Prockop are limited to administering only cells and do not specifically teach administering the culture supernatant that they cannot be combined with the teaching of Kobayashi. Applicant requests that the Examiner reconsider this argument because claim 11 has been amended to include exosomes and Kobayashi do not teach the inclusion of exosomes. Applicant asserts that a prima facie case of obviousness has not been established because there is no proper reason or rationale that would allow one of ordinary skill in the art to arrive at the claimed invention.
This is not found persuasive. First, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In the current case, both Kobayashi and Prockop are drawn to the treatment of ocular disorders with the therapeutic properties of mesenchymal stem cells as described above.
Prockop teach that administration of their MSC-derived compositions can vary and include intraocular administration over a period of time (administration period) and can include multiple administrations, including daily dosages (one or more times a day), for a period of time to provide a therapeutic effect (page 49, page 54). Prockop teach that it should be understood that their methods may be carried out in a number of ways and with various modifications and permutations well known in the art (page 40).
Therefore one of ordinary skill in the art would have been motivated to modify the administration of the ocular symptom improving agent in the method of Kobayashi to include daily administrations over the course of a time period found to provide a therapeutic effect for the improvement of myopia, presbyopia and astigmatism because Prockop teach and suggest that multiple administrations, including daily dosages (one or more times a day), for a period of time to provide a therapeutic effect are suitable and beneficial for treatment methods of these ocular disorders with a MSC culture supernatant. One of ordinary skill in the art would have had a reasonable expectation of success because Prockop indicate that MSCs can be obtained from any source (page 32) and that they secrete therapeutic proteins (page 18, page 40, page 47) and Kobayashi is also using the culture supernatant of a MSC culture for an ocular improving agent.
Second, evidence that the culture supernatants of MSCs, and specifically dental pulp stem cells, include exosomes that contain the therapeutic proteins of the MSCs is provided by Tomarev et al as described above and also by Applicant’s own Specification at paragraph 27.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA J SCHUBERG whose telephone number is (571)272-3347. The examiner can normally be reached 8:30-5:00 EST.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631