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 .
The amendment filed 15 April 2026 is acknowledged and has been entered.
Status of the Claims
Claims 1-221, 224 and 238 have been cancelled.
Claims 240 and 241 have been withdrawn.
New claims 242 and 243 have been submitted.
Claims 222, 223, 225-238 and 242-243 are presented for examination on the merits.
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 222, 223, 225-238 and 242-243 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.
Claim 222 is rendered vague and indefinite by the phrase “wherein the FMT has an odor as evaluated with a confidence of 95% to be odorless for more than 50% of the population using a triangular test, wherein the FMT has a flavor as evaluated with a confidence of 80% to be flavorless for more than 50% of the population using the triangular test”.
It is unclear how this is meant to define the scope of the claimed FMT. Does the composition have an odor 5% of the time? How is one to know if one is within the scope of the claimed invention? Is performing the triangular test a requirement of the claim? It is further confusing in how dependent claims 232 and 233 are meant to further limit the claim scope.
Claim 231 is rendered vague and indefinite by the phrase “FMT has a color that substantially colorless”. Substantially is a relative term and a matter of degree, while color is not. That is- beige can be considered light brown, but it is still a color of its own.
The claim language has been changed from “a color that is different from human fecal matter”. Presumably this is meant convey that the FMT is not brown like human feces. But even if the brownness is removed it would still have color. Thus “substantially colorless” is contradictory.
All other claims depend directly or indirectly from rejected claims and are, therefore, also rejected under U.S.C. 112, second paragraph, for the reasons set forth above.
“[W]here there is a great deal of confusion and uncertainty as to the proper interpretation of the limitations of a claim, it would not be proper to reject such a claim on the basis of prior art. As stated in In re Steele, 35 F.2d 859, 134 USPQ 292 (CCPA 1962), a rejection under 35 USC 103 should not be based on considerable speculation about the meaning of terms employed in a claims or assumptions that must be made as to the scope of the claims.” MPEP 2173.06 II.
Given the indefiniteness of the claim scope, it is difficult to determine if the FMT of the prior art reads on the FMT of the current claims. However, in order to expedite prosecution the closest prior art is put forward in the following rejection.
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.
Claim 222, 223, 225-238 and 242-243 are rejected under 35 U.S.C. 103 as being unpatentable over Jones et al. (10,905,726).
Jones et al. beneficially teaches oral Microbiota restoration therapy (MRT) compositions and methods for manufacturing MRT compositions. Examples include the steps of: collecting a stool sample; purifying the stool sample to form a purified intermediate, wherein purifying the stool sample comprises: adding a diluent to the stool sample; mixing the stool sample and diluent to form a mixture; filtering the mixture; transferring a filtrate from the filtering step to a centrifuge tube; and centrifuging the filtrate to arrive at the purified intermediate; lyophilizing the purified intermediate to form a plurality lyophilized pellets; and encapsulating the plurality of lyophilized pellets in one or more capsules.
Filtering the mixture comprises filtering the mixture to obtain a sample having particles in the range of 50 to 70 micrometers.
Centrifuging the filtrate comprises centrifuging the filtrate at a rate such that the centrifugal force is in the range of about 8-12,000 g for in the range of 15 to 45 minutes.
Lyophilizing the purified intermediate comprises the steps of:
mixing the purified intermediate with a lyophilization excipient (e.g., at least 2.3% PEG 3350, 1% glycerin, 10% trehalose, and 10% sucrose to form a lyophilization intermediate;
placing the lyophilization intermediate into a plate having a plurality of wells;
lowering a temperature of the lyophilization intermediate to a temperature in the range of −40 to −45° C.;
applying a vacuum to the lyophilization intermediate and raising the temperature of the lyophilization intermediate to approximately 0° C.;
initializing a secondary drying step and raising the temperature of the lyophilization intermediate to approximately 25° C.;
releasing the vacuum; and
removing a plurality of lyophilized pellets from the plate.
Lyophilization excipient comprises
The human fecal material is optionally filtered prior to its use in the microbiota restoration therapy. Once the sample has been processed to have a particle size of approximately 60 μm or less, the sample may then be washed and further concentrated using a centrifuge. In some instances, centrifuge tubes may have a volume in the range of 50 to 500 mL, or more. The filtered suspension is filled to approximately 20 to 80% of the volume of the centrifuge tube. In one example, the samples may be centrifuged at 1100 to 3600 revolutions per minute (rpm) for 10 to 15 minutes cycles. In another example, the samples may be centrifuged at a rate such that the centrifugal force is in the range of about 8-12,000 g (e.g., about 10,000 g) for 15-45 minutes or 20-30 minutes. The centrifuge may be ramped up or gradually accelerated to the speed needed to create a centrifugal force in the range of about 8-12,000 g (e.g., about 10,000 g). It is further contemplated that the centrifuge may also be slowly ramped down or decelerated when the centrifugation process is complete. In some instances, it may be desirable to decelerate the centrifuge as slowly as possible so that the return to atmospheric pressure is slow so as to protect the bacterial cells from potentially bursting. The supernatant is removed and the remaining material in the tube is the purified intermediate MRT composition. This may result in a product that has been concentrated by approximately 60%. In some instances, the centrifugation process may be a 2-tiered process. For example, the product may first undergo a “pre-spin” (for example 300 g for 2-5 minutes) to remove fecal fibrous material and then may undergo a longer centrifugation to concentrate the product. It is further contemplated that volumes of up to 300 mL may be centrifuged without resulting in a drop in the amount of concentration. The resulting MRT composition is a bacterial suspension having a particle size of 70 μm or less and a bacterial concentration on the order of approximately 1×1010 CFU/g. The resulting MRT composition may also be stable for 3 weeks at refrigeration conditions.
In some embodiments, centrifugation alone can be used multiple times for purification and concentration.
In some instances, lyophilization, or freeze-drying, may be used to convert the sample from a liquid to a solid. The sample may be provided with a cryoprotectant such as, but not limited to PEG, skim milk, charcoal, ascorbic acid or a combination thereof to protect the bacteria from the effects of freezing. The sample may also be provided with a lyoprotectant such as, but not limited to sucrose, inositol, trehalose, glycerol, or a combination thereof.
Since the USPTO is not equipped to manufacture products by the myriad processes put before it and then obtain prior art products and make comparisons therewith, a lesser burden of proof is required to make out a case of prima facie anticipation/obviousness for the product-by-process claims because of their peculiar nature than when a product is claimed in the conventional manner. MPEP 2113. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the Application to administer an oral FMT preparation with minimized fecal odor and color based on the teaching Jones et al.
In KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court emphasized a flexible approach to the obviousness question, stating that the analysis under 35 U.S.C. § 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418; see also id. at 421 ("A person of ordinary skill is... a person of ordinary creativity, not an automaton."). In KSR, the Supreme Court indicated that the obviousness analysis should consider the “background knowledge possessed by a person having ordinary skill in the art.” KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398 (2007). Under KSR, information deemed within PHOSITA’s general knowledge is more powerful than that found buried in a prior art reference because we assume that PHOSITA would consider using their general knowledge in combination with the prior art — even absent any express motivation to do so. Under 35 U.S.C. § 103, the obviousness inquiry turns not only on the prior art, but whether “the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious . . . to a person having ordinary skill in the art to which the claimed invention pertains.” 35 U.S.C. § 103. Regardless of the tribunal, the inquiry into whether any “differences” between the invention and the prior art would have rendered the invention obvious to a skilled artisan necessarily depends on such artisan’s knowledge. See Philips v. Google & Microsoft 2020. The adjustment of particular conventional working conditions (e.g., determining optimum conditions such as centrifuge speed, filtration conditions, etc. depending on the desired result) is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan.
The prior art is silent regarding the amount of odor of the disclosed oral FMT; however, given the amount of purification of the feces and the fact that it is used orally it is presumed to be odorless or at least as odorless as the claimed FMT. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1254-1255, 195 U.S.P.Q. (BNA) 430, 432-33 (C.C.P.A. 1977).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of skill in the art at the time the invention was made, as evidence by the references, especially in the absence of evidence to the contrary (e.g., criticality of the various conditions employed in the preparation method).
Response to Arguments
Applicant’s amendments/arguments, with respect to the indefiniteness rejections have been fully considered and are persuasive. The 35 USC 112(b) rejections of the previous Office action have has been withdrawn.
However, the amendments made to the claims have introduced some new indefiniteness issues and the claims remain unclear for the reasons set forth above.
Applicant's amendments/arguments filed with respect to the prior art rejection have been fully considered but they are not persuasive.
Applicant submits that a person having ordinary skill in the art would have recognized that the encapsulated FMT of Jones cannot be in direct contact with a subject's tongue. Additionally, Jones does not consider odor or taste of the FMT, failing entirely to mention sensory evaluation.
This is unpersuasive, since anyone working in the field of FMT would find it obvious to minimize the inherent undesirable odor/flavor of human feces if the administration is going to be oral. Furthermore, the fact that Jones discloses the possibility of employing common forms of oral administration does not mean that the FMT does not come into contact with the tongue during oral administration. Indeed, Jones teaches the form of tablets, which is now in new claim 242.
The claims are not limited to administration of FMT only, but a composition that contains it, such as a comestible. That is – it is encapsulated into another form such as a tablet. Does Applicant really mean that the FMT that is found to have an odor/flavor for most people is being administered directly, without putting it into a more acceptable form?. How does it come into direct contact with the tongue if it is administered in these other forms?
For the sake of expediting prosecution it is suggested that Applicant’s invention is predicated on an unexpected result, - an unpredictable phenomenon, highly dependent upon specific proportions and/or amounts of particular ingredients. With respect to such unexpected results, please note that in KSR, the Court also reaffirmed that evidence of unexpected results may overcome an examiner's prima facie case of obviousness. KSR, 550 U.S. at 416 ("The fact that the elements worked together in an unexpected and fruitful manner supported the conclusion that Adams' design was not obvious to those skilled in the art" - discussing United States v. Adams, 383 U.S. 39). However, "any superior property must be unexpected to be considered as evidence of non-obviousness." Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1371 (Fed. Cir. 2007). Thus, "[m]ere improvement in properties does not always suffice to show unexpected results ....[W]hen an applicant demonstrates substantially improved results.., and states that the results were unexpected, this should suffice to establish unexpected results in the absence of evidence to the contrary." In re Soni, 54 F.3d 746, 751 (Fed. Cir. 1995). Moreover, in order to establish unexpected results for claimed invention, objective evidence of non-obviousness must be commensurate in scope with the claims which the evidence is offered to support. In re Greenfield, 571 F.2d 1185, 1189 (CCPA 1978). Please also note that "the discovery of an optimum value of a variable in a known process is usually obvious." Pfizer v. Apotex, 480 F.3d at 1368. The rationale for determining the optimal parameters for prior art result effective variables "flows from the 'normal desire of scientists or artisans to improve upon what is already generally known.'" Id. (quoting In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)).
Thus it is suggested that the claims employ a product-by-process form to define FMT that was found to be substantially odorless/flavorless to distinguish the Applicant’s FMT, instead of the convoluted statistical result language. That is, specifically provide the steps employed as well as the critical variables (i.e, centrifugation speed, duration, etc.) instead of the vague broad ranges recited in claim 239.
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.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUSSELL G FIEBIG whose telephone number is (571)270-5366. The examiner can normally be reached M-F 8-4.
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/RUSSELL G FIEBIG/ Examiner, Art Unit 1655
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