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 .
Response to Arguments
Applicant's arguments filed 5/7/2026 have been fully considered but they are not persuasive. On pages 6 and 7 of the Applicant’s Arguments, the Applicant states that evidentiary references Mehmood and Tarvati cannot apply because they are not directly drawn to viable cells, but rather small molecules and proteins. First, and foremost, there is absolutely no requirement in the claims or specification that the composition include a specific number of viable cells, which would include zero viable cells; the definition of “microbiota restoration therapy,” in the specification, states that it “may include, but not limited to, human fecal material containing viable gut flora.” See page 7, lines 24-26. This would suggest that viable microbiota is one embodiment, and should not be construed as the scope of the claimed invention. Second, as was discussed in the previous Office Action, Borody 1 and Borody 2 both explicitly and unambiguously teach lyophilization, and one, or more, of the claimed additives; Mehmood and Tarvati were used to show that these compounds are well-known, and widely-used, wherein they possess known and predictable impacts on lyophilization procedures. Since these compounds were discussed in Borody 1 and 2, wherein these references clearly and unambiguously teach lyophilization with a lyoprotectant, it stands to reason that well-known and widely-used lyoprotectants could be predictably applied. Since Mehmood and Tarvati teaches lyoprotectants that overlap with those explicitly mentioned in Borody 1 and 2, it would be, at the very least obvious to try, wherein the predictable outcome would be acting as a lyoprotectant. Finally, Borody 1 explicitly states that “stabilizers” are used to “reduce destruction of living bacteria,” suggesting that the additive would improve cell viability. See paragraph [0157].
On page 7 of the Applicant’s Arguments, the Applicant states that the Examiner incorrectly categorized excipients as inert. While this is true, it does not negate the fact that Borody 1 and 2 teach the claimed compounds.
On pages 8-10 of the Applicant’s Arguments, the Applicant contends that the claimed combinations provided for unexpected improvements. If the argument that the claimed combinations provide for unexpected improvements, the fact that there is no data showing the viability using individual lyoprotectants makes it impossible to assess the veracity of this statement. Furthermore, both Borody 1 and 2 make it clear that lyoprotectants are necessary and further provide examples of these compounds that align with the claimed compounds. Both Mehmood and Tarvati indicate that it is not non-obvious to use combinations of known lyoprotectants. Since the Applicant has not shown data of individual lyoprotectants, and some of the shown/claimed combinations provide for poor protection (half the combinations of Table 6, especially PEG and glycerol), this argument is not persuasive.
On page 10 of the Applicant’s Arguments, the Applicant argues improper hindsight reasoning. All of the Applicant’s claimed lyoprotectants are known. All of the claimed lyoprotectants are behaving as lyoprotectants and added for the purpose of lyoprotection. Mehmood and Tarvati show that the claimed combinations of known lyoprotectants have been considered by the ordinary artisan. All of the provided data appears to show a predictive additive improvement in lyoprotection. As the Applicant has not shown the same testing using individual lyoprotectants, there is no reasonable manner for the Office to accurately compare the cited results with those of individual lyoprotectants.
On page 11 of the Applicant’s Arguments, the Applicant argues that the excipients of Borody I are alternatives. First, there is nothing in Borody 1 to suggest that if one compound is used, it is used exclusively. Second, the paragraphs cited in the arguments do not support the Applicant’s assertion, in the sense that Borody 1 uses compounds “for freezing,” as “stabilizers” and a specific additive named for cryoprotection. Borody never states that a stabilizer and cryoprotectant cannot be used together, in fact, the ordinary artisan would be motivated to include both, because there would be a reasonable expectation that there would be a combination of cryoprotection and stabilization to “reduce destruction of living bacteria.” For example, it does not seem like it would be non-obvious to use polyethylene to stabilize the bacterial cells and trehalose as a cryoprotectant. See Borody 1, paragraph [0157] [0167]. There is nothing in Borody 1 to suggest that they should not be combined; and based upon Borody 1 and the general knowledge that the Examiner assumes an ordinary artisan possesses, there would be a reasonable expectation that the polyethylene would stabilize the cell, while the trehalose helped provided cryoprotection (for note, it is assumed the ordinary artisan possesses a Masters or PhD in a related field of microbiology and possesses ample applied experience in the field, including lyophilization techniques. This is reasonable to assume, since lyophlilization of bacterial compositions has been a standard practice for many decades. See MPEP 2141.03). Furthermore, all of this ignores that the other cited prior art shows that individually and combinations of the claimed compounds are already known and used for the purposes of lyophilization.
On page 12 of the Applicant’s Arguments, the Applicant argues that the Examiner is engaging in impermissible hindsight reasoning, and argues that Borody 2’s list in a “length laundry list.” With respect to the argument of impermissible hindsight reasoning, see the paragraph before the previous paragraph. With respect to the claim that Borody 2 provides a “laundry list.” As there is no definition of “laundry list” in the MPEP, the Examiner disagrees that the length is too long to make it obvious to the ordinary artisan. It is contended, that based on Borody 2 and the other cited art, the claimed combinations would be obvious; this is underscored by the fact that Borody 2 is not considered in a vacuum, but is considered based upon the other cited prior art, and the knowledge the Examiner assumes an ordinary artisan possesses, the combination would be obvious and predictable.
On page 13 of the Applicant’s Arguments, the Applicant states that the Examiner is providing a highly speculative rejection. The Applicant has provided a limitation that is an inherent property to the composition being claimed. The limitation does not appear to limit the claimed composition’s structure or ingredients; that is to say, if the composition possesses the claimed excipients, and has been lyophilized, it will possess the claimed glass transition temperatures. Based upon the instant specification, this assessment appears to be true. Therefore, if the prior art motivates the ordinary artisan to create a composition that is consistent with that claimed, it must inherently provide for these features. Since the Office does not have laboratories to test the obviousness and predictability of hypothetical combinations, the Examiner can only assess what is printed and what appears to be inherent to a method or composition. Since the rejection is based upon a combination of references that lead the ordinary artisan to the claimed invention, there is no reasonable expectation that the prior art would teach a hypothetical combination’s glass transition temperature. However, since the Examiner has provided motivation to combine, then the hypothetical combination should possess the same inherent features as the claimed composition. See MPEP 2112. For example, the ordinary artisan knows that the lyoprotectant trehalose increases the glass transition temperature.
For the reasons provided above, and the reproduced rejections below, all claims are rejected.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 21, 24-27, 33, 34, 37-43, 46, and 49-55 are rejected under 35 U.S.C. 103 as being unpatentable over Borody (PGPub 2013/0195804 [Borody 1]) and Borody (WO 2014/078911 [Borody 2]) and evidenced by Mehmood, et al (Open Science Journal of Pharmacy and Pharmacology, 3, 19-27, 2015) and Taravati, et al (World Applied Sciences Journal 2, 353-363, 2007). Borody 1 teaches methods of microbiota restoration by providing a treated fecal microbiota composition. See paragraph [0001]. Borody indicates that it can be administered by the oral route and can be provided as a lyophilize composition. See paragraph [0042] [0136]. Borody 1 indicates that the composition can include compounds that help reduce the destruction of living bacteria, which can be polyethylene glycol, and sugars that include the monosaccharide components of sucrose. See paragraph [0157]. Borody 1 indicates that trehalose can be used as a cryoprotectant. See paragraph [0167]. Borody 1 indicates that glycerol is added as a stabilizing agent and to help reduce the formation of ice crystals in the lyophlizatsion process/ See paragraph [0147] [0156]. Although Borody teaches glucose and fructose (to aid in bacteria survival), the monosaccharide components of the disaccharide sucrose, Borody 1 is silent towards sucrose. Since each of the 3 named ingredients of Borody 1 are all used for different purposes, there is nothing in Borody 1 to suggest that these should be used separately. Furthermore, the ordinary artisan possesses ample knowledge of fecal processing and lyophilization, and as such, would find the inclusion of known compounds already used in lyophilization and cryopreservation as being obvious, since the ordinary artisan is fully aware of their uses and functions. See MPEP 2141.03
Borody 2 provides for a method that overlaps with Borody 1, wherein methods of providing fecal microbiota are taught. See page 1, lines 5-23. Borody 2 provides the composition by oral route. See page 17, line 16. Borody 2 indicates that the composition can be provided in a lyophilized form. See page 9, line 27. Borody 2 indicates that various sugars, including sucrose and trehalose can be used; Borody 2 also indicates that both polyethylene glycol and glycerol can be added to the composition. See page 21, lines 1-3. Borody 2 notes that polyethylene glycol can be used for delayed or gradual enteric release. See page 27, line 19. Borody 2 states that glycerol is used to stabilize the composition. See page 32, line 30. Borody 2 does not state the purpose for including trehalose or sucrose, but generally suggests that these can be used as lyoprotectants and food for the microbiota. See page 7, line 3; page 20, lines 28-32 (continuing to page 21, lines 1 and 2; page 23, line 14. As such, even though Borody 2 is broadly describing the inclusion of these sugars, and is not explicitly teaching the inclusion of sucrose with the other claimed compounds, the uses of these compounds are well-described, known and predictable.
To elaborate on the predictability of these compounds, both Mehmood and Taravati teach these compounds as well-known, and widely-used, excipients that possesses highly predictable outcomes when included in a composition.
Mehmood provides a review that discusses common excipients for lyophilized pharmaceutical compositions. See page 19, “Abstract” section. Mehmood notes all of the claimed excipients and describes their well-known and highly-predictable uses in lyophilization methods. See page 20 and 21. Mehmood also presents a table of well-known drugs, and the various combinations of excipients used, in order to elicit certain properties. See Table 3. Based upon this, there is no reason to expect that the ordinary artisan would find the inclusion of multiple well-known excipients to by non-obvious. Furthermore, since all of the claimed excipients have well-known and highly predictable physical properties, especially when used in lyophilization methods, the claimed combination would have been obvious to the ordinary artisan.
Taravati, similarly, provides a review paper discussing how various well-known and widely-used excipients affect the stability of a protein. See page 353, “Abstract” section. Specifically, Taravati notes that sucrose, trehalose and glycerol are all known to aid in stabilizing proteins. See page 353, right column, last paragraph. As such, Taravati provides even more evidence that the claimed excipients provide for highly predictable behaviors.
Since it has been shown that all of the claimed compounds can be used in a method of providing fecal microbiota to a subject, using a lyophilized product, either individually, and all of their respective behaviors are well-known to the ordinary artisan, their inclusion in a larger composition would be both predictable and obvious. It would be obvious because each compound has overlapping, yet different, functions, wherein their specific inclusion to a composition would yield predictable results.
If the Applicant believes that the claimed composition yields result that would not be predicted by the prior art, the Applicant should present this evidence; however, barring evidence of unexpected properties, the claimed method should be predictable. This predictability must be underscored by the fact that “excipient” is generally defined as an inert additive.
With respect to claims 21, 25-27, 33, and 34 the cited prior art teaches the claimed method. Providing the composition by the oral route suggests the use of a capsule.
With respect to claims 24, 30, 37 and 40, Borody teaches polyethylene glycol. Although no specific form is described, the properties of the claimed form would be well-known and predictable to the ordinary artisan. There is no evidence to suggest that the claimed form provides for any unexpected benefits.
With respect to claims 43, 46 and 49, Borody 2 suggests including mineral salts. See page 7, line 3. Since NaCl is a common salt that is essential for life, it would be obvious to include.
With respect to claims 50-55, based upon Mehmood, the glass transition temperature of the claimed excipients is known. See Table 1. Since all of these compounds are well-known, with highly predictable (and well-documented) physical properties, their glass transition temperature would be obvious. Furthermore, the ordinary artisan, who possesses ample knowledge in pharmaceutical formulations, would find particular temperature more suitable for the method of Borody than others. It is highly probable that the composition of Borody provides for a glass transition temperature with an overlapping range.
Conclusion
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 DAVID W BERKE-SCHLESSEL whose telephone number is (571)270-3643. The examiner can normally be reached M-F 8AM-5:30PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DAVID W BERKE-SCHLESSEL/Primary Examiner, Art Unit 1651
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