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 .
DETAILED ACTION
Applicant’s amendment filed on 06 November 2025 is entered. Claim 1 is amended, and claim 62 is new.
Claims 1-2, 7-9, 13, 59, and 62 are pending and under examination.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06 November 2025 has been entered.
Claim Rejections - 35 USC § 103
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.
Claims 1-2, 7-9, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Kweon et al. (US 20170333492 A1, published 23 November 2017) in view of Malo et al. (Intestinal alkaline phosphatase promotes gut bacterial growth by reducing the concentration of luminal nucleotide triphosphates, Am J Physiol Gastrointest Liver Physiol. 2014 May 15;306(10):G826-38. doi: 10.1152/ajpgi.00357.2013. Epub 2014 Apr 10).
Regarding claims 1, 7-8, and 13, Kweon teaches a method for treating metabolic diseases comprising administering isolated human commensal gastrointestinal bacteria Bacteroides acidifaciens to a subject in need thereof (Kweon claim 11). Kweon confirms that the Bacteroides acidifaciens is an intestinal symbiotic bacteria (i.e. from human GI-tract) (Kweon [0204]). Kweon teaches that isolated Bacteroides acidifaciens may be administered as the active ingredient in a pharmaceutical composition to treat metabolic diseases such as obesity, diabetes, and metabolic syndrome (Kweon claims 1-2), and that the diabetes can be type 1 or type 2 (Kweon [0029]).
However, Kweon does not teach their method to comprise co-administering bovine intestinal alkaline phosphatase (IAP).
Malo teaches that administering IAP can normalize gut flora and promote the growth of a wide range of intestinal commensal bacteria (Malo Pg. G826 para. 1). Malo also teaches that the IAP administered in their experiments was bovine IAP (bIAP) (Malo Pg. G827 para. 2).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to administer bovine intestinal alkaline phosphatase (bIAP) together with human commensal gastrointestinal bacteria Bacteroides acidifaciens to treat metabolic diseases, including obesity, type 1 and type 2 diabetes, and metabolic syndrome, in a subject in need thereof. One of ordinary skill in the art would have been motivated to so because adding bIAP to the composition comprising Bacteroides acidifaciens would advantageously promote the growth of intestinal symbiotic bacteria Bacteroides acidifaciens in the subject administered the composition. One of ordinary skill in the art would have a reasonable expectation of success because Kweon taught that compositions comprising Bacteroides acidifaciens can be used in a method of treating metabolic diseases and Malo taught that bIAP can advantageously promote the growth of a wide range of intestinal commensal bacteria, such as Bacteroides acidifaciens taught by Kweon.
Regarding claim 2, Kweon teaches that the administered bacterial composition may be from fecal microbiota transplanted (FMT) in their examples (Kweon [0099], [0177], and Fig. 21).
Regarding claim 9, Kweon teaches that the Bacteroides acidifaciens can be cultures of the bacteria (Kweon [0026]).
Claims 59 and 62 are rejected under 35 U.S.C. 103 as being unpatentable over Kweon in view of Malo as applied to claims 1-2, 7-9, and 13 above, and further in view of Mueller et al. (US 7202072 B2, published 10 April 2007).
Neither Kweon nor Malo explicitly teach that the bIAP comprises an amino acid sequence having at least about 97% sequence identity to instant SEQ ID NO: 11.
However, Mueller teaches an intestinal alkaline phosphatase comprising an amino acid sequence that aligns 100% to the amino acid sequence of instant SEQ ID NO: 11 (Mueller SEQ ID NO: 2, see alignment below Qy=instant SEQ ID NO: 11, Db = SEQ ID NO: 2 of Mueller). Mueller also teaches that their SEQ ID NO: 2 encodes a highly active bovine IAP (Mueller Col. 6 lns. 66-67).
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Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to use the bIAP having amino acid sequence SEQ ID NO: 2 of Mueller in the method of Kweon modified by Malo as discussed above. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because Mueller taught that the bIAP of amino acid sequence SEQ ID NO: 2 is an advantageously highly active bovine IAP, and thus would have the advantageous benefit of greatly promoting the growth of the intestinal commensal bacteria Bacteroides acidifaciens used as the active ingredient in the method of Kweon in view of Malo.
Response to Arguments
Applicant's arguments filed 06 November 2025 have been fully considered but they are not persuasive.
Regarding Applicant’s arguments that one of ordinary skill in the art would have no reason to believe that administering AP would help combat a disease characterized by high levels of AP (Remarks pg. 4 para. 1-3), Kweon teaches that Bacteroides acidifaciens is administered to treat metabolic diseases. AP is not taught to be administered to treat the diseases, but rather as a helpful agent that promotes the growth of intestinal commensal bacteria like Bacteroides acidifaciens as taught by Malo. The rejection does not state that one of ordinary skill in the art would be motivated to administer AP alone to treat the metabolic diseases. One of skill in the art would not have avoided introducing AP just because the diseases are characterized by high AP, especially in light of the art’s recognition that high AP is not the reason these metabolic diseases exist, nor does high AP exacerbate or otherwise negatively affect the outcomes of the disease. As discussed in previous arguments, Applicant’s cited references Kim, Chen, and Gurler all suggest that high levels of AP is a good marker of metabolic diseases, but none of them suggest that high AP would be harmful. Thus, in view of the prior art, one of ordinary skill in the art would have been motivated to administer AP in combination with the Bacteroides acidifaciens administered in the method of Kweon because Malo taught that AP promotes the growth of intestinal commensal bacteria, including Bacteroides acidifaciens.
Regarding Applicant’s arguments that the conclusion that AP promotes the growth of Bacteroides acidifaciens is pure speculation without any supporting evidence (Remarks pg. 5 paras. 3-4), Malo provides sufficient evidence for one of ordinary skill in the art to conclude that AP promotes the growth of intestinal commensal bacteria (Malo Pg. G826 para. 1). Kweon confirms that the Bacteroides acidifaciens is an intestinal symbiotic bacteria (i.e. from human GI-tract) (Kweon [0204]). Thus, one of ordinary skill in the art would reasonably conclude that administration of AP as taught by Malo would beneficially promote the growth of Bacteroides acidifaciens since it is an intestinal symbiotic bacteria. The conclusion is based on the combination of prior art references. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Regarding Applicant’s arguments that Gurler highlights the unpredictability of the field, stating that “the relationship between obesity and alkaline phosphatase (ALP) is controversial” and Chen notes that “Previous studies have reported inconsistent results of the associations of AP with incident type 2 diabetes” (Remarks pg. 4 paras. 4-5 and pg. 7 para. 1), as stated above, AP is not being used to treat the metabolic disease. Bacteroides acidifaciens is administered to treat metabolic diseases. AP is only administered as a helpful agent that promotes the growth of intestinal commensal bacteria like Bacteroides acidifaciens as taught by Malo. Any unpredictability in the field regarding the associations of AP and metabolic diseases are not tantamount to unpredictability in the treatment of metabolic diseases by administering Bacteroides acidifaciens. The evidence presented in the prior art and in Applicant’s cited Exhibits do not point to AP being harmful or an ingredient that might exacerbate the metabolic diseases being treated by administering Bacteroides acidifaciens. Mere statements about controversiality and unpredictability are insufficient to surmount the conclusions drawn on evidence.
Regarding Applicant’s argument that exhibitory references Kim et al., Chen et al., and Gurler et al. (provided in IDS dated 20 December 2024) would have motivated one of ordinary skill in the art to avoid administering exogenous IAP for fear that it would make a metabolic disorder worse, and thus would not have been motivated with reasonable expectations of success to combine the teachings of Kweon, Malo, and Mueller because the field allegedly teaches that IAP may have a negative effect on metabolic disorders (Remarks Pgs. 5-6), Kim et al. teaches that no mechanism for alkaline phosphatase association with metabolic syndrome has been elucidated. (Kim Pg. 321 para. 2 sent. 5). Kim teaches that elevated AP levels are associated with metabolic syndrome (Kim Table 1). Kim does not provide any evidence nor any suggestion that AP causes or exacerbates metabolic syndrome. Rather, Kim suggests that the associations of AP with metabolic syndrome are that AP is a marker of visceral obesity or hepatic steatosis, or AP is a marker of subclinical inflammation (Kim p. 326 para. 1 sent. 1). Thus, one of ordinary skill in the art would conclude that the elevated levels of AP that are associated with metabolic syndrome are good markers for the disease, but would not conclude that AP causes or exacerbates metabolic syndrome.
Chen et al. teaches that elevated levels of AP has been found in diabetes patients, but notes that other studies show no significant association between AP and diabetes (Chen Pg. 2 para. 2.); thus the association of elevated AP levels with diabetes is unpredictable. Chen teaches that elevated AP can be a predictor of diabetes (Chen Pg. 4 Description para. 1 sent. 1). Chen therefore teaches that AP is associated with diabetes, but provides no evidence nor suggestion that AP is a causative or exacerbating agent for diabetes. Thus, one of ordinary skill in the art would conclude that the elevated levels of AP that are associated with diabetes are good predictors for diabetes, but would not conclude that AP causes or exacerbates diabetes.
Gurler et al. teaches that AP levels are not associated with insulin resistance, but rather might be a response to elevated parathormone levels (Gurler Abstract). Therefore, Gurler does not demonstrate AP causes or exacerbates insulin resistance at least because Gurler teaches that AP levels are note associated with insulin resistance.
Thus, one of skill in the art would not have avoided introducing IAP just because it has been taught to be a good marker of metabolic diseases. Rather, one of skill in the art would have been motivated to administer IAP because the art teaches IAP’s beneficial effect of promoting the growth of intestinal bacteria such as Bacteroides acidifaciens, which is taught by Kweon to be suitable to treat metabolic disorders. In view of the art, one of ordinary skill in the art would not have concluded that exogenous IAP would make a metabolic disorder worse, and thus would still have been motivated a with reasonable expectation of success to combine the teachings of Kweon, Malo, and Mueller to co-administer Bacteroides acidifaciens and IAP to treat metabolic disorders.
Regarding Applicant’s argument that Example 1 of Applicant’s specification demonstrated that IAP can favor the survival and expansion of bacteria known to ameliorate metabolic syndrome, weight loss, and type 2 diabetes and the results of Figure 2 demonstrated that Bacteroides acidifaciens was not eliminated, but rather proliferated, in the IAP co-administered mice even after streptomycin treatment, and that those results were unexpected in view of the teachings of the cited references (Remarks P g. 6 last sentence through pg. 7 para. 1), Malo already taught that administering IAP can normalize gut flora and promote the growth of a wide range of intestinal commensal bacteria (Malo Pg. G826 para. 1), and Kweon already taught that the intestinal commensal bacteria Bacteroides acidifaciens was able to treat metabolic syndrome, obesity, and type 1 and type 2 diabetes. Thus, contrary to Applicant’s argument, the art already recognized the results and these are not unexpected results.
Conclusion
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/Alexander M Duryee/Examiner, Art Unit 1657
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
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