Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Applicant’s amendment submitted on 11/24/2025 is acknowledged. Claims 36 and 51 are currently amended. Claims 1-35, 37-41, and 48 are canceled. Claims 36, 42-47, and 49-52 remain pending in 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.
New Rejection Necessitated by Amendment: Claims 51-52 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 51 recites the limitations “under the same conditions” in lines 8, 11-12, and 14-15. It is not clear if “the same conditions” is intended to refer to the conditions caused by an infection with Helicobacter pylori in a human or an animal as recited in the preamble or if it refers to conditions under which co-aggregates are formed between Helicobacter pylori and Lactobacillus reuteri DSM 17648. Thus, the metes and bounds of the claim are unclear. Applicant’s amendment should clearly reflect if the conditions recited in lines 8, 11-12, and 14-15 refer to the conditions caused by an infection as recited in the preamble or if it refers to co-aggregation conditions.
Claim 52 is also rejected for being dependent on a rejected base claim and failing to remedy the issues set forth above.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Maintained Rejection: Claims 36, 42-44, 46-47, and 49-52 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Boettner (US2007/0148149; Applicant IDS; Of Record) in view of Teixeira (Journal of Applied Bacteriology, 1995; Of Record) as evidenced by Holz et al. (Probiotics & Antimicro. Prot., 2015, Vol. 7, p.91-100; Of Record).
Regarding claims 36, 42-43, 47 and 49-50, Boettner teaches compositions comprising Lactobacillus cells which are capable of aggregating Helicobacter pylori under conditions of the human digestive tract and use of such compositions (see Abstract). Boettner teaches administering its pharmaceutical composition comprising viable Lactobacillus cells to a person for the prophylaxis and/or treatment of diseases caused by infection with Helicobacter pylori (see para [0023] and Claim 14). Boettner teaches the Lactobacillus strains to be selected from DSM 17646, DSM 17647, DSM 17648, DSM 17649, DSM 17650, DSM 17651, DSM 17652 and DSM 17653, and demonstrates their examples with DSM 17648 (see para [0021], Examples 2-4, and Claim 1). Boettner teaches DSM 17646, DSM 17649, DSM 17652 and DSM 17653 are Lactobacillus brevis strains (see para [0021] – reads on claim 42). Even though Boettner discloses DSM 17648 is a Lactobacillus fermentum strain (see para [0021]), in light of the instant amended claim 36, Boettner teaches a Lactobacillus reuteri strain when disclosing DSM 17648 (for evidence - see Abstract of Holz). Boettner teaches the bacteria to be present in lyophilized/freeze-dried form (see paras [0024]-[0027]). Boettner teaches the Lactobacillus strains in its compositions are capable of binding to free Helicobacter pylori to form aggregates in culture conditions of the stomach, reading on wherein co-aggregates are formed between Helicobacter pylori and Lactobacillus reuteri DSM 17648 and claim 47 (see para [0017]). Boettner further teaches lyophilization of Lactobacillus has no effect on its H. pylori aggregation ability (see para [0044]). Boettner further teaches the size of the co-aggregates comprising Lactobacillus and H. pylori to be between 1 µm to 1,000 µm and more (see paras [0020], [0038], and Fig. 1A – reads on wherein the co-aggregates are larger than 50 µm and the limitations of claims 49-50). Boettner teaches these large aggregates can no longer reach and infect epithelial cells in the stomach and therefore prevents gastritis, stomach cancers, and stomach ulcers (see paras [0018] and [0023]). Boettner teaches administering the same Lactobacillus strains as in instant claims to a person to treat Helicobacter pylori infections and teaches its compositions forms aggregates with Helicobacter pylori in culture conditions of the stomach. Therefore, it is expected that Boettner’s methods would also result in the formation of co-aggregates of its compositions with Helicobacter pylori in situ after application in the stomach medium, reading on claim 43.
Boettner teaches the bacteria to be present in lyophilized form (freeze-dried) but does not teach the bacteria to be in spray-dried form.
However, spray drying is an alternative and known technique in the art to prepare bacterial compositions. Teixeira teaches that spray-drying is an alternative method to freeze drying and compares the viability of Lactobacillus bulgaricus bacteria when prepared by the two methods (see Abstract and Table 1). Teixeira teaches by comparison of the two methods, spray-drying and freeze-drying (lyophilized), in terms of survival, acid production and extent of the lag phase, no significant differences were obtained (see p.460, left column, 4th paragraph, p.461, left column, 2nd paragraph). Teixeira also teaches spray-drying is preferable to freeze-drying because it has a lower cost and that spray-drying of lactic acid bacteria dates back to 1914 (p.456, left column, 1st paragraph).
Therefore, it would have been obvious to one of ordinary skill in the art, at the time of the instant invention, to modify the compositions of Boettner and prepare the bacteria in the compositions of Boettner using spray-drying instead of freeze-drying. One of ordinary skill in the art would have been motivated to do so because the artisan is using a known alternative drying method to prepare the bacteria and it is cheaper compared to freeze drying as taught by Teixeira. Since Boettner teaches the same Lactobacillus strains as instantly claimed and the strains in freeze-dried form are capable to form aggregates with H. Pylori, it would have been reasonable to expect that spray-dried bacteria would also cause aggregates, since Teixeira teaches by comparison of the two methods, spray-drying and freeze-drying (lyophilized), in terms of survival, acid production and extent of the lag phase, no significant differences were obtained.
With respect to the limitations “wherein the co-aggregates are larger in size compared to using the same composition comprising non-spray-dried Lactobacillus reuteri DSM 17648” and “wherein the co-aggregates are larger than 50 µm,” the limitations pertaining to the size of the co-aggregates are intended outcomes of the recited method. Boettner teaches administering its pharmaceutical composition comprising viable Lactobacillus cells to a person for the prophylaxis and/or treatment of diseases caused by infection with Helicobacter pylori (see para [0023] and claim 14) and teaches the same Lactobacillus strain, DSM 17648, (see para [0021]) as instantly claimed). Boettner teaches the Lactobacillus strains in its compositions are capable of binding to free Helicobacter pylori to form aggregates in culture conditions of the stomach (see para [0017]). Teixeira teaches that lactic acid bacteria are commonly spray-dried and is an alternative technique to freeze-drying. The combined teachings of Boettner in view of Teixeira teach the same method steps of preparing spray-dried bacterial compositions (same strain - DSM 17648) and administering it to a subject to treat H. pylori as instantly claimed. Therefore, it is expected that the method of Boettner in view of Teixeira would also result in the co-aggregates being the same size as instantly recited in the claimed invention.
Regarding claim 44, Boettner teaches the compositions can be prepared as pharmaceutical compositions comprising suitable active substances (see para [0025]).
Regarding claim 46, the limitation that the “Lactobacillus cells are essentially present in monomer and/or dimer form” is an intended outcome of the spray-drying method. Since Boettner teaches the same Lactobacillus strains as instantly claimed and Teixeira teaches that lactic acid bacteria are commonly spray-dried and is an alternative technique to freeze-drying, the combined teachings of Boettner in view of Teixeira teach the same method steps of preparing the bacterial compositions (same strains) as instantly claimed. Therefore, it is expected that the composition as prepared by the teachings of Boettner in view of Teixeira would also result in a composition wherein the “Lactobacillus cells are essentially present in monomer and/or dimer form”.
Regarding claims 51-52, Boettner teaches compositions comprising Lactobacillus cells which are capable of aggregating Helicobacter pylori under conditions of the human digestive tract and use of such compositions (see Abstract). Boettner teaches administering its pharmaceutical composition comprising viable Lactobacillus cells to a person for the prophylaxis and/or treatment of diseases caused by infection with Helicobacter pylori (see para [0023] and Claim 14). Boettner teaches the Lactobacillus strains to be selected from DSM 17646, DSM 17647, DSM 17648, DSM 17649, DSM 17650, DSM 17651, DSM 17652 and DSM 17653, and demonstrates their examples with DSM 17648 (see para [0021], Examples 2-4, and Claim 1). Boettner teaches DSM 17646, DSM 17649, DSM 17652 and DSM 17653 are Lactobacillus brevis strains (see para [0021]). Even though Boettner discloses DSM 17648 is a Lactobacillus fermentum strain (see para [0021]), in light of the instant amended claim 36, Boettner apparently teaches a Lactobacillus reuteri strain when disclosing DSM 17648 (for evidence - see Abstract of Holz). Boettner teaches the bacteria to be present in lyophilized/freeze-dried form (see paras [0024]-[0027]). Boettner teaches the Lactobacillus strains in its compositions are capable of binding to free Helicobacter pylori to form aggregates in culture conditions of the stomach, reading on wherein co-aggregates are formed between Helicobacter pylori and Lactobacillus reuteri DSM 17648 (see para [0017]). Boettner further teaches lyophilization of Lactobacillus has no effect on its H. pylori aggregation ability (see para [0044]). Boettner further teaches the size of the co-aggregates comprising Lactobacillus and H. pylori to be between 1 µm to 1,000 µm and more (see paras [0020], [0038], and Fig. 1A – reads on wherein the co-aggregates are larger than 50 µm as recited in claim 51). Boettner teaches these large aggregates can no longer reach and infect epithelial cells in the stomach and therefore prevents gastritis, stomach cancers, and stomach ulcers (see paras [0018] and [0023]). With respect to the limitations “under the same conditions”, Boettner teaches administering the same Lactobacillus strains as in the instant claims to a person to treat Helicobacter pylori infections and teaches its compositions form aggregates with Helicobacter pylori in culture conditions of the stomach, observing that lyophilization does not affect aggregation ability.
Boettner teaches the bacteria to be present in lyophilized form (freeze-dried) but does not teach the bacteria to be in spray-dried form.
However, spray drying is an alternative and known technique in the art to prepare bacterial compositions. Teixeira teaches that spray drying is an alternative method to freeze drying and compares the viability of Lactobacillus bulgaricus bacteria when prepared by the two methods (see Abstract and Table 1). Teixeira teaches by comparison of the two methods, spray-drying and freeze drying (lyophilized), in terms of survival, acid production and extent of the lag phase, no significant differences were obtained (see p.460, left column, 4th paragraph, p.461, left column, 2nd paragraph). Teixeira also teaches spray drying is preferable to freeze drying because it has a lower cost and that spray drying of lactic acid bacteria dates back to 1914 (p.456, left column, 1st paragraph).
Therefore, it would have been obvious to one of ordinary skill in the art, at the time of the instant invention, to modify the compositions of Boettner and prepare the bacteria in the compositions of Boettner using spray-drying instead of freeze-drying. One of ordinary skill in the art would have been motivated to do so because the artisan is using a known alternative drying method to prepare the bacteria and it is cheaper compared to freeze drying as taught by Teixeira. Since Boettner teaches the same Lactobacillus strains as instantly claimed and the strains in freeze-dried form are capable to form aggregates with H. Pylori, it would have been reasonable to expect that spray-dried bacteria would also cause aggregates, since Teixeira teaches by comparison of the two methods, spray drying and freeze drying (lyophilized), in terms of survival, acid production and extent of the lag phase, no significant differences were obtained.
With respect to the limitations “wherein the co-aggregates are larger in size compared to using the same composition comprising non-spray-dried Lactobacillus reuteri DSM 17648,” “wherein the co-aggregates have increased stability compared to using the same composition comprising non-spray-dried Lactobacillus reuteri DSM 17648,” and “wherein the degree of co-aggregation is more than twice that compared to using a composition comprising non-spray-dried Lactobacillus reuteri DSM 17648,” these limitations are intended outcomes of the recited method. Boettner teaches administering its pharmaceutical composition comprising viable Lactobacillus cells to a person for the prophylaxis and/or treatment of diseases caused by infection with Helicobacter pylori (see para [0023] and claim 14) and teaches the same Lactobacillus strain, DSM 17648, (see para [0021]) as instantly claimed). Boettner teaches the Lactobacillus strains in its compositions are capable of binding to free Helicobacter pylori to form aggregates in culture conditions of the stomach (see para [0017]). Teixeira teaches that lactic acid bacteria are commonly spray-dried and is an alternative technique to freeze-drying. The combined teachings of Boettner in view of Teixeira teach the same method steps of preparing spray-dried bacterial compositions (same strain - DSM 17648) and administering it to a subject to treat H. pylori as instantly claimed. Therefore, it is expected that the method of Boettner in view of Teixeira would also result in the co-aggregates having the same properties as recited in claim 51, under the same conditions.
Therefore, the combination of Boettner and Teixeira renders claims 36, 42-44, 46-47, and 49-52 prima facie obvious.
Maintained Rejection: Claim 45 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Boettner (US2007/0148149; Applicant IDS; Of Record) in view of Teixeira (Journal of Applied Bacteriology, 1995; Of Record) as evidenced by Holz et al. (Probiotics & Antimicro. Prot., 2015, Vol. 7, p.91-100; Of Record), as applied to claims 36, 42-44, 46-47, and 49-52 above, and further in view of Lesbros-Pantoflickoba (J. Nutrit., 2007, Vol. 137, p.812S-818S; hereinafter LP; Of Record).
Boettner in view of Teixeira teach the invention of claims 36 and 44 as discussed in the rejection above.
Regarding claim 45, neither Boettner nor Teixeira teach said suitable active ingredients are antibiotics.
LP teaches combination treatments with probiotics (Lactobacillus) and antibiotics reduces side effects and improves Helicobacter pylori eradication (see Abstract, p.814S, right column, last two paragraphs, p.815S, left column, last two paragraphs, full right column, and Table 4). LP further teaches probiotic treatment with Lactobacillus decreases H. pylori bacterial loads and reduces frequency of diarrhea (see p.815S, paragraph bridging left and right columns,-right column, 3rd paragraph). Furthermore, LP teaches growth of Helicobacter pylori is inhibited by Lactobacillus reuteri by inhibiting the binding of H. pylori to glycolipid receptors (see p.813S, right column, 1st paragraph, and Table 1).
Therefore, it would have been obvious to one of ordinary skill in the art, at the time of the invention, to modify the method of prophylaxis and/or treatment of diseases caused by infection with Helicobacter pylori by administering the Lactobacillus composition of Boettner in view Teixeira to include antibiotics as taught by LP, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to because LP teaches the combination of Lactobacillus and antibiotics is effective at improving H. pylori eradication and reducing side effects, which would yield predictable results. Furthermore, it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. See MPEP § 2144.06.
Thus, the combination of Boettner, Teixeira, and LP renders claim 45 prima facie obvious.
Response to Arguments
Applicant's arguments filed 11/24/2025 have been fully considered but they are not persuasive.
In Applicant’s Remarks, see p.5, 2nd paragraph, and the paragraph bridging pp.5-6, Applicant argues that Boettner does not teach or suggest using spray-dried Lactobacillus reuteri cells (let alone Lactobacillus reuteri DSM 17648 cells of the amended claims) to form co-aggregates with H. pylori. Applicant argues that Teixeira does not teach or suggest using Lactobacillus reuteri cells (let alone Lactobacillus reuteri DSM 17648 cells of the amended claims), nor using spray-dried Lactobacillus reuteri to form co-aggregates with H. pylori. Applicant further argues they have clearly made a contribution to the field, since none of the prior art teach or suggest using the claimed spray-dried Lactobacillus reuteri DSM 17648 cells for the treatment of an infection by H. pylori. Applicant further argues the Office has failed to show that the art as a whole would teach or suggest using the selected strains of the claimed invention and would have expected the same results as Applicant discloses. This is not found persuasive.
Boettner teaches the Lactobacillus strains to be selected from DSM 17646, DSM 17647, DSM 17648, DSM 17649, DSM 17650, DSM 17651, DSM 17652 and DSM 17653, and demonstrates their examples with DSM 17648 (see para [0021], Examples 2-4, and Claim 1). While Boettner discloses DSM 17648 is a Lactobacillus fermentum strain (see para [0021]), in light of the instant amended claim 36, Boettner apparently teaches a Lactobacillus reuteri strain when disclosing DSM 17648. Holz’s Abstract provides evidence that the Lactobacillus strain DSM17648 is a Lactobacillus reuteri strain. Boettner teaches the bacteria to be present in lyophilized/freeze-dried form (see paras [0024]-[0027]). Boettner teaches the Lactobacillus strains in its compositions are capable of binding to free Helicobacter pylori to form aggregates in culture conditions of the stomach, reading on wherein co-aggregates are formed between Helicobacter pylori and Lactobacillus reuteri DSM 17648 (see para [0017]). Boettner further teaches lyophilization of Lactobacillus has no effect on its H. pylori aggregation ability (see para [0044]). While Boettner does not teach the Lactobacillus DSM 17648 is in spray-dried form, Teixeira teaches that spray-drying is an alternative method to freeze-drying and compares the viability of Lactobacillus bulgaricus bacteria when prepared by the two methods (see Abstract and Table 1). Teixeira teaches by comparison of the two methods, spray-drying and freeze-drying (lyophilized), in terms of survival, acid production and extent of the lag phase, no significant differences were obtained (see p.460, left column, 4th paragraph, p.461, left column, 2nd paragraph). Teixeira also teaches spray-drying is preferable to freeze-drying because it has a lower cost and that spray-drying of lactic acid bacteria dates back to 1914 (p.456, left column, 1st paragraph). Therefore, it would have been obvious to one of ordinary skill in the art, at the time of the instant invention, to modify the compositions of Boettner and prepare the bacteria in the compositions of Boettner using spray-drying instead of freeze-drying. One of ordinary skill in the art would have been motivated to do so because the artisan is using a known alternative drying method to prepare the bacteria and it is cheaper compared to freeze drying as taught by Teixeira. Since Boettner teaches the same Lactobacillus strains as instantly claimed and the strains in freeze-dried form are capable to form aggregates with H. Pylori, it would have been reasonable to expect that spray-dried bacteria would also cause aggregates, since Teixeira teaches by comparison of the two methods, spray-drying and freeze-drying (lyophilized), in terms of survival, acid production and extent of the lag phase, no significant differences were obtained. Thus, one of ordinary skill in the art would have been motivated to spray-dry the Lactobacillus strains of Boettner, including Lactobacillus DSM 17648, in order to provide a cheaper method of obtaining dried cells with no significant differences in the dried cells. Considering Boettner teaches the lyophilization process has no effect on the ability of Lactobacillus to form aggregates with H. pylori, an ordinarily skilled artisan would have a reasonable expectation of success modifying the Lactobacillus DSM 17468 of Boettner to be spray-dried rather than lyophilized and would have yielded the expectable results in terms of aggregation with H. pylori and aggregate size. Therefore, the claimed invention is prima facie obvious over Boettner in view of Teixeira.
In Applicant’s Remarks, see p.6, 1st paragraph,-p.7, 2nd paragraph, Applicant argues that Teixeira teaches that spray-drying in general is not a commercial means of preparing lactic acid bacteria because of low survival rates. Applicant further argues that the skilled artisan would have known from the prior art available that survival of bacterial strains to spray-drying is unpredictable and dependent on strain selection. Applicant further argues that comparing the survival between spray-dried and freeze-dried Lactobacillus bulgaricus strains described in Teixeira is immaterial to the Lactobacillus reuteri strains in the pending claims in view of survivability of spray-dried Lactobacillus being unpredictable. Applicant further argues that obviousness under 35 U.S.C. § 103 requires that the combination of references would have yielded nothing more than predictable results, and is not possible since Teixeira states “[f]urther investigation is necessary to try to protect the membrane from injury” (p.461, left column, last paragraph). This is not found persuasive.
While Teixeira relates to L. bulgaricus, Teixeira is only relied upon to teach the technique of spray-drying. Boettner is modified by Teixeira to teach spray-dried L. reuteri cells, taught as Lactobacillus DSM 17648, for use in treating infection by H. pylori, as claimed in the present invention. It is the combination of Boettner in view of Teixeira that teach a spray-dried L. reuteri DSM 17648. Boettner is modified in view of Teixeira to teach a spray-dried L. reuteri rather than a freeze-dried L. reuteri as originally taught by Boettner. Teixeira does not state that spray-drying cannot be a commercial means of preparing LAB, only that it has not yet been developed. Teixeira states low survivability is mainly the reason behind spray-drying not being developed commercially, but not the only reason. Teixeira finds no significant difference in the survival of freeze-dried vs. spray-dried cells (see p.460, left column, 4th paragraph, p.461, left column, 2nd paragraph). Thus, one of ordinary skill in the art would have reasonably expected little differences between freeze-dried (lyophilized) and spray-dried lactic acid bacteria within the context provided by Teixeira. Furthermore, Teixeira teaches spray-drying of lactic acid bacteria dates back to 1914, thus the drying technique has been known in the relevant field (see p.456, left column, 1st passage). Additionally, the process of spray-drying does not have to be commercial in order to satisfy the claimed invention. See MPEP 2145(VII). While spray-drying may be inconsistent across all bacteria and depends on strain selection, Teixeira provides motivation for an ordinarily skilled artisan to modify the teaching of Boettner in view of Teixeira’s teaching that there are no significant differences between spray-drying and freeze-drying. The assertion that Teixeira’s teachings are immaterial to the present invention is not persuasive because Teixeira compares freeze-drying and spray-drying in a lactic acid bacterium which L. reuteri is and the nature of the teaching is highly relevant. With respect to Teixeira’s statement that “[f]urther investigation is necessary to try to protect the membrane from injury”, Teixeira prefaces that comparison of spray-drying and freeze-drying demonstrated that “in terms of survival, acid production and extend of the lag phase, no significant differences were obtained.” Accordingly, the ordinarily skilled artisan would have a reasonable expectation of success of preserving the survivability of the spray-dried Lactobacillus.
In Applicant’s Remarks, see p.7, 3rd paragraph,-p.8, 1st paragraph, Applicant argues that the Office has provided no teaching in the prior art of a nexus between survival and aggregation, nor any teaching in the prior art the spray-dried bacteria (living or dead) are capable of aggregation with Helicobacter pylori. Applicant further argues that the prior art teaches heat treatment of spray-drying causes additional damage and stress to bacteria that doesn’t occur during freeze-drying. Applicant concludes that the impact of heat damage from spray-drying Lactobacillus reuteri DSM 17648 cells on the ability to co-aggregate with Helicobacter pylori was completely unknown and could not be predicted prior to Applicant’s invention. This is not found persuasive.
The arguments regarding a nexus between survival and aggregation have been discussed in the responses above. With regards to the prior art teaching heat treatment of spray-drying causing additional damage and stress to bacteria that is absent in freeze-drying, the prior art cited does not teach away from spray-drying. In fact, the prior art is general and states spray-drying can be detrimental and has the same stresses mentioned during freeze-drying. Moreover, the prior art cited does not, with certainty, teach that spray-drying damages cells and mentions the potential for damage to cells. Therefore, it could not be said that spray-drying has always detrimental effects and should be avoided or that freeze-drying should be ultimately preferred. Furthermore, none of the citations from the prior art cited are with regards to Lactobacillus bacteria, and thus Applicant makes assertions taken out of context from the art.
In Applicant’s Remarks, see p.8, 2nd paragraph,-p.9, last paragraph, Applicant argues that they surprisingly discovered that spray-dried Lactobacillus reuteri DSM 17648 co-aggregates with Helicobacter pylori and that the co-aggregates are larger in size, more stable, and co-aggregate at a larger degree. Applicant argues this is a significant contribution to the art because improved co-aggregation provides better inhibition/reduced colonization of the stomach lining by Helicobacter pylori. Applicant argues that Boettner did not demonstrate an increase in co-aggregate size when comparing fresh-culture to lyophilized Lactobacillus in Example 4 of Boettner. Applicant further argues that instant Example 3 surprisingly demonstrates increased size of co-aggregates and improved stability of co-aggregates using spray-dried L. reuteri DSM 17648. Applicant argues the Boettner essentially uses the same protocols as the Applicant, and thus are directly comparable to Applicant’s disclosure. Applicant further argues instant Example 5 demonstrates a surprising doubling of degree of co-aggregation using spray-dried L. reuteri DSM 17648. Applicant argues that Boettner did not find an increase in co-aggregate size when comparing fresh culture of L. reuteri to lyophilized L. reuteri. Applicant argues that the fresh culture in Boettner disclosed in paragraph [0038] resulted in aggregates usually from 5 to 50 μm in size, which is outside of the range of the claimed invention. Applicant concludes that spray-dried L. reuteri DSM 17648 have surprisingly improved aggregation properties over the prior art and were unexpected. This is not found persuasive.
The examples of Boettner demonstrate aggregates having sizes from 1 μm to 50 μm and even to 1000 μm and more, and thus the size of aggregates were realized in the prior art (see Example 2, paragraphs [0038], and Fig. 1A). Moreover, Boettner demonstrates that lyophilization had no effect on the ability of Lactobacillus to aggregate H. pylori (see Example 4). The fact that lyophilization had no effect on the ability of Lactobacillus DSM17648 to aggregate with H. pylori, and that it was known that typical aggregates can have a size of 1000 μm and more, it follows that the lyophilized Lactobacillus DSM 17648 would also comprise these features. While Boettner is silent as to the average or typical size of aggregates formed by lyophilized Lactobacillus DSM 17648 in Example 4, Boettner explicitly discloses in paragraph [0020] that aggregates have a size of at least 1 μm to 1000 μm and more, which certainly appreciates aggregate sizes of the claimed invention. Thus, the increased size of the aggregates is not an unexpected result as evidenced by Boettner. Furthermore, it would have been obvious to spray-dry the Lactobacillus cells of Boettner rather than lyophilize the cells as discussed above. One of ordinary skill in the art would not have expected surprising results in the ability of aggregation from what Boettner discloses about the effect of lyophilization in paragraph [0044] and Teixeira’s findings that freeze-drying (lyophilization) and spray-drying are not significantly different. Applicant did not demonstrate that the properties of aggregation of H. pylori between spray-dried and lyophilized Lactobacillus is surprising, and only showed the differences between fresh culture and spray-dried Lactobacillus. Boettner only discloses that lyophilized DSM 17648 did not affect the capability of DSM17648 to induce aggregation, and thus does not make an admission of the average aggregate size using lyophilized DSM 17648. Thus, the ordinarily skilled artisan can only infer that the aggregate sizes of lyophilized DSM 17648 would be in the range as disclosed in Boettner, which clearly overlaps that of the claimed invention. Therefore, Applicant’s argument that the spray-dried form yields unexpected results is not persuasive because the modification to spray-dry, as taught by Teixeira, the DSM 17648 cells of Boettner, would be expected to yield aggregate sizes and capabilities overlapping those observed by Applicant.
For these reasons, the 35 U.S.C. § 103 rejections are maintained.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN PAUL SELWANES whose telephone number is (571)272-9346. The examiner can normally be reached Mon-Fri 7:30-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise W. Humphrey can be reached at 571-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/J.P.S./Examiner, Art Unit 1657
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