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 .
Status of the Claims
Claims 4 and 7 are pending.
Claims 4 and 7 have been examined on their merits.
Withdrawn Objections & Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application. Any objections or rejections not specifically reiterated are hereby withdrawn.
The rejection of claims 4 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (Plos One, 2019) in view of Li et al. (Journal of Agricultural Food Chemistry, 2009) and Su et al. (The Journal of Pharmaceutical and Experimental Therapeutics, 2006) are maintained as discussed below.
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 4 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (Plos One, 2019) in view of Li et al. (Journal of Agricultural Food Chemistry, 2009) and Su et al. (The Journal of Pharmaceutical and Experimental Therapeutics, 2006).
In regards to claim 4, Yu teaches a composition for maturing embryos comprising sodium butyrate (Title, Abstract, p1; Experimental Design, p5-6).
In regards to the difference between sodium butyrate (which is the salt of butyric acid, also called butyrate), it is noted that as taught by Li, tributyrin is a pro-drug of butyrate, that consists of three butyric acids esterified to a glycerol (Introduction, p9243). As further taught by Li, there is an interest in developing pro-drug derivatives of butyrate that are more efficacious, that tributyrin is approved as an additive in the US and Canada, that that it is known in the art that tributyrin can be used as a culture supplement (Introduction, 9244).
This is confirmed by Su who teaches that tributyrin is a butyrate pro-prodrug with butyrate being its metabolite (Abstract, p62). Additionally, as taught by Su, in comparison to butyrate, tributyrin not only has more favorable pharmacokinetic properties and is better tolerated, but also demonstrates more potent activity in vitro (Introduction, p63). Furthermore, Su teaches that cells can be cultured in 0.1 mM (which is the same as 100 µmol/L) (Fig. 5, p68), which overlaps with the claimed range.
Therefore, taken together, a person of ordinary skill in the art would have been motivated to substitute sodium butyrate with tributyrin because it would be longer lasting with better more efficacious activity. Furthermore, because both Li and Su indicate that cell can be cultured with tributyrin (which results in the same effect, a source of butyric acid), a person of ordinary skill in the art could have substituted sodium butyrate with tributyrin with predictable results and a reasonable expectation of success.
In regards to claim 7, Yu teaches the medium comprises KSOM media (Experimental Design, p5-6).
Therefore, the combined teachings of Yu, Li, and Su renders the invention unpatentable as claimed.
Response to Arguments
Applicant argues, “Yu teaches a composition for maturing embryos including sodium butyrate, while the instant application discloses an in vitro embryonic development culture medium including tributyrin . . . Yu does not contain any mention, teaching, or suggestion of tributyrin, let alone its application in embryo culture at any concentration, particularly not at the claimed 100 µmol/L . . . Yu provides no guidance or incentive for a skilled artisan to look beyond sodium butyrate toward tributyrin, a chemically distinct compound (a triglyceride pro-drug, not a salt) (Remarks, p3).
Applicant therefore concludes, “[T]he Examiner's substitution of tributyrin for sodium butyrate is therefore based on impermissible hindsight, rather than any teaching in Yu itself” (Remarks, p3).
Applicant’s arguments filed 08/192026 have been fully considered but are not found persuasive.
As discussed above, Yu teaches a composition for maturing embryos comprising sodium butyrate (Title, Abstract, p1; Experimental Design, p5-6).
In regards to the difference between sodium butyrate (which is the salt of butyric acid, also called butyrate), it is noted that as taught by Li, tributyrin is a pro-drug of butyrate, that consists of three butyric acids esterified to a glycerol (Introduction, p9243).
As further taught by Li, there is an interest in developing pro-drug derivatives of butyrate that are more efficacious, that tributyrin is approved as an additive in the US and Canada, that that it is known in the art that tributyrin can be used as a culture supplement (Introduction, 9244).
This is confirmed by Su who teaches that tributyrin is a butyrate pro-prodrug with butyrate being its metabolite (Abstract, p62). Additionally, as taught by Su, in comparison to butyrate, tributyrin not only has more favorable pharmacokinetic properties and is better tolerated, but also demonstrates more potent activity in vitro (Introduction, p63). Furthermore, Su teaches that cells can be cultured in 0.1 mM (which is the same as 100 µmol/L) (Fig. 5, p68), which overlaps with the claimed range.
Therefore, taken together, a person of ordinary skill in the art would have been motivated to substitute sodium butyrate with tributyrin because it would be longer lasting with better more efficacious activity. Furthermore, because both Li and Su indicate that cell can be cultured with tributyrin (which results in the same effect, a source of butyric acid), a person of ordinary skill in the art could have substituted sodium butyrate with tributyrin with predictable results and a reasonable expectation of success.
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).
Applicant argues, “[T]ributyrin is a prodrug that typically requires esterases to release its active metabolite, butyrate. Although Li and Su teach that tributyrin is a prodrug of butyrate, such teachings are established in the context of in vivo circulatory systems rich in esterase activity, or cancer cell culture systems supplemented with serum. In contrast, claim 4 of the instant application is directed to a static in vitro embryo culture environment, which typically employs serum-free or low-protein media that lack the substantial esterase activity present in the aforementioned prior art systems. Therefore, a person of ordinary skill in the art could not have reasonably expected that tributyrin would be efficiently converted to butyrate in this particular in vitro environment, let alone that it would promote blastocyst formation” (Remarks, p3-4).
Applicant argues that combining Yu with Li and Su would result in a direct technical contradiction because Yu teaches the use of sodium butyrate in embryonic development, while Li and Su teach that tributyrin (at concentrations above 0.1 mM) exhibits anticancer cytotoxicity, which Applicant argues is a teaching away (Remarks, p4).
Specifically, in regard to Li, Applicant argues that the reference refers specifically to cancer cell culture or anticancer efficacy and that nothing in Li suggests that tributyrin can be used as a supplement in normal embryo culture. Applicant also argues that "additive" approval in Li refers to an oral food additive, not an embryo culture medium additive which has no bearing on its biological safety or efficacy when directly supplemented into an in vitro embryo culture medium (Remarks, p4-5).
Specifically, in regards to Su, Applicant argues that this reference is limited to in vivo administration, which lacks scientific basis. Applicant also argues that the teachings of Su refer to cytotoxicity/anticancer activity in malignant cells, and therefore, are a teaching away (Remarks, p5-6).
Applicant’s arguments filed 08/192026 have been fully considered but are not found persuasive.
In regards to Applicant’s arguments regarding in vivo contexts, as discussed above, both Li and Su teach that tributyrin is a known in vitro additive (see Li, Introduction, p9243 and Su, Introduction, p63).
In regards to Applicant’s arguments regarding cancer cell in vitro treatments and their inapplicability to culturing embryos, the claims are drawn to a composition not method. The claims do not require embryos, and do not require steps of culturing embryos and obtaining specific effects. Instead, the preamble only states “An in vitro embryonic development culture medium for promoting embryo development” which an intended use.
Additionally, according to MPEP 2111.02, to satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997) (anticipation rejection affirmed based on Board’s factual finding that the reference dispenser (a spout disclosed as useful for purposes such as dispensing oil from an oil can) would be capable of dispensing popcorn in the manner set forth in appellant’s claim 1 (a dispensing top for dispensing popcorn in a specified manner)).
In the instant case, as taught by both Li and Su, it was known in the art that tributyrin was capable of being used as an in vitro supplement and therefore are capable of performing this intended use.
Furthermore, again as above, tributyrin is a known butyrate pro-prodrug with butyrate being its metabolite and as specifically taught by Yu compositions comprising butyrate for maturing embryos were known in the art (Title, Abstract, p1; Experimental Design, p5-6).
Therefore, it would have been predicably obvious to substitute tributyrin for butyric acid in a media composition as discussed above.
In regards to allegations of “teaching away”, a reference does not teach away if it merely expresses a general preference but does not criticize, discredit or otherwise discourage investigation into the invention claimed.”) (see MPEP 2145(X)(D)(1)).
Continuing, in regards to Su, Applicant argues that the teaching of 0.1 mM is the starting point, which only demonstrated marginal inhibition, but that the IC50 was between 1.6 and 1.0 mM (Remarks, p5). Therefore, Applicant argues that Su does not teach that the cited concentration of 0.1 mM would have any specific biological effect for promoting embryo development (Remarks, p5).
Applicant’s arguments filed 08/192026 have been fully considered but are not found persuasive.
As noted by Applicant, 0.1 mM tributyrin is a specific concentration for use in an in vitro media. Therefore, it would have been predictably obvious to use this concentration in a composition as discussed above.
Applicant argues that Claim 4 of the instant application using the tributyrin in the culture medium to significantly promote embryo development (e.g., increasing blastocyst rate from 69.53% to 86.07%) is therefore unexpected and non-obvious. Relatedly, Applicant argues that the medium aims to reduce ROS, improve mitochondrial membrane potential, and increase blastocyst rates (Remarks, p4-5).
Applicant’s arguments filed 08/192026 have been fully considered but are not found persuasive.
As discussed above, the claims are drawn to a composition not method. The claims do not require embryos, and do not require steps of culturing embryos and obtaining specific effects. Instead, the preamble only states “An in vitro embryonic development culture medium for promoting embryo development.”
However, according to MPEP 2111.02, to satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997) (anticipation rejection affirmed based on Board’s factual finding that the reference dispenser (a spout disclosed as useful for purposes such as dispensing oil from an oil can) would be capable of dispensing popcorn in the manner set forth in appellant’s claim 1 (a dispensing top for dispensing popcorn in a specified manner)).
Conclusion
No claims are allowed.
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 JOSEPH (PAUL) MIANO whose telephone number is (571)272-0341. The examiner can normally be reached Mon-Fri from 8:30am to 5:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Doug) Schultz can be reached at (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
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