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 .
Status of the Claims
Claims 1-15 responsive to communications on 04/14/2023 are pending.
Claims 1-15 have been examined on their merits.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3-6, 11-12, and 14-15 are rejected under 35 U.S.C. 102(a)(1) or 35 U.S.C. 102(a)(2) as being anticipated by de la Rosa et al. (US20170121685A1, 2017, on IDS 07/13/2023).
In regards to claims 1 and 14, de la Rosa discloses a medium for culturing MSCs (animal cells) to derive exosomes (a type of extracellular vesicle) comprising DMEM (a basal medium) and at least the additive insulin (paragraph [0093]; claim 7).
In regards to the limitation “wherein the concentration of L-glutamine or salt thereof is 5 mM or more in the culture medium”, since claim 1 is limited to “at least one component selected from L-glutamine . . . transferrin, etc.”, the claim does not necessarily require L-glutamine, and therefore, does not specifically require the concentration of L-glutamine either (it is noted that claim 3, which is discussed below, does require this limitation).
In regards to claims 3-6 and 11-12, de la Rosa discloses that the medium comprises at least insulin, transferrin and selenium (selenious acid) (paragraph [0093]).
In regards to claim 15, de la Rosa discloses methods for producing extracellular vesicles (Claim 7; paragraph [0093]).
Therefore, de la Rosa anticipates the invention as claimed.
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 2 is rejected under 35 U.S.C. 103 as being unpatentable over de la Rosa et al. (US20170121685A1, 2017, on IDS 07/13/2023) in view of Dos Santos et al. (Stem Cell Rev and Rep, 2017).
De la Rosa anticipates claim 1 as discussed above.
In regards to claim 2, de la Rosa teaches that the medium comprises glutamine (L-glutamine) (paragraph [0093]).
In regards to the concentration, it is noted that as above in claim 1, if the embodiment comprises L-glutamine, then the claimed concentration is 5mM. To this regard, de la Rosa teaches that the concentration of L-glutamine is 2mM (paragraph [0093]). While less than a concentration of 5mM or more, it is nonetheless close, and according to MPEP 2144.05(I), a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985).
Furthermore, a person of ordinary skill in the art could have arrived at a concentration of 5 mM or greater and the disclosure does not point to a criticality in this concentration.
In regards to routine optimization, MPEP 2144.05(II)(A), generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
In the instant case because do Santos teaches that MSCs can be cultured in a range of concentrations including at least 10 mM L-glutamine (Abstract, p482; Fig. 1, p485), which overlaps with the range of at least 5 mM L-glutamine, a person of ordinary skill in the art could have arrived at a concentration of 5 mM or greater by routine optimization with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of de la Rosa and dos Santos renders the invention unpatentable as claimed.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over de la Rosa et al. (US20170121685A1, 2017, on IDS 07/13/2023) in view of Ma et al. (Aging, 2019).
De la Rosa anticipates claim 1 as discussed above.
In regards to claim 7, de la Rosa does not explicitly teach that the medium comprises insulin-like growth factor.
However, a person of ordinary skill in the art would have been motivated to include insulin-like growth factor (IGF) because Ma teaches that exosomes produced in media supplemented with IGF demonstrate anti-inflammatory and anti-apoptotic effects and in particular, inhibit neuroinflammation and have neuroprotective effects (Abstract, p12278; Fig. 2, p12280; Figure 3, p12282-12283).
Furthermore, because Ma teaches that stem cells can be cultured in media comprising IGF (Preparation and characterization of IGF-Exo, p12279) and that it is known in that MSC-derived exosomes promote neurovascular reshaping and functional recovery after stroke (Introduction, p12278), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of de la Rosa and Ma renders the invention unpatentable as claimed.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over de la Rosa et al. (US20170121685A1, 2017, on IDS 07/13/2023) in view of Glustafsson et al. (Journal of Cellular Biochemistry, 2006).
De la Rosa anticipates claim 1 as discussed above.
In regards to claim 8, de la Rosa does not explicitly teach that the medium comprises serotonin.
However, a person of ordinary skill in the art would have been motivated to include serotonin in the media because Glustafsson teaches that serotonin supplementation promotes proliferation of MSCs (Abstract, p139; Fig. 7, p147).
Furthermore, because Glustafsson teaches that serotonin can be added to media for culturing MSCs (Proliferation Assays, 142; Fig. 7, p147).) and de la Rosa are in the same technical field culturing MSCs, it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of de la Rosa and Glustafsson renders the invention unpatentable as claimed.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over de la Rosa et al. (US20170121685A1, 2017, on IDS 07/13/2023) in view of Zhang et al. (Journal of Cellular Physiology, 2018).
De la Rosa anticipates claim 1 as discussed above.
In regards to claim 9, de la Rosa does not explicitly teach that the medium comprises TGF-β.
However, a person of ordinary skill in the art would have been motivated to include TGF-β in the media because Zhang teaches that exosomes derived MSCs stimulated with TGF-β promotes Treg differentiation (Title, Abstract, p6832; Preparation of conditioned medium, p6834; Fig. 6, p6837).
Furthermore, because Zhang teaches methods for producing media comprising TGF-β for culturing MSCs (Preparation of conditioned medium, p6834) and de la Rosa and Zhang are in the same technical field of deriving exosomes from MSCs, it could have been done with predictable results and a reasonable expectation of success.
Therefore, de la Rosa and Zhang renders the invention unpatentable as claimed.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over de la Rosa et al. (US20170121685A1, 2017, on IDS 07/13/2023) in view of Ludwig et al. (International Journal of Molecular Science, 2019) and Hoang et al., Frontiers in Molecular Biosciences, 2020.
De la Rosa anticipates claim 1 as discussed above.
In regards to claim 10, de la Rosa teaches that the medium comprises serum (paragraph [0093]).
However, Ludwig teaches that there are exosomes present in fetal bovine serum (FBS) itself and that they are biologically active and that that co-isolation may lead to interference in subsequent in vitro or in vivo studies; that FBS can have confounding effects on highly sensitive gene profiling technologies; and that not only FBS in culture supernatants but also proteins present in serum or plasma or any body fluid used as a source of extracellular vesicles can “contaminate” exosomes leading to artefactual data in downstream applications, especially in mass spectrometry (Medium Composition, p4-5). Therefore, a person of ordinary skill in the art would have been motivated to use serum free conditions in order avoid this contamination.
Furthermore, because Hoang teaches that MSCs can be specifically cultured in serum-free conditions for the derivation of exosomes (Title, Abstract, p1; Figure 4, p8), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of de la Rosa, Ludwig, and Hoang renders the invention unpatentable as claimed.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over de la Rosa et al. (US20170121685A1, 2017, on IDS 07/13/2023) in view of Shpall et al. (WO2019099927, on IDS 05/06/2024).
De la Rosa anticipates claim 1 as discussed above.
In regards to claim 13, de la Rosa does not explicitly teach the composition as a kit.
However, a person of ordinary skill in the art would have been motivated to incorporate the composition into a kit because Shpall teaches that kits comprising compositions for deriving MSCs exosomes can be used to administer exosome compositions (paragraph [00176]). Furthermore, kits for media compositions are well-known in the art and it would have been obvious to combine components into a kit for the purpose of convenience and economy. Furthermore, because Shpall teaches that kits for preparing exosomes can be made (paragraph [00176]), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of de la Rosa and Shpall renders the invention unpatentable as claimed.
Conclusion
No claims are allowed.
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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631