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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1/8/2026 has been entered.
Status of Claims
Currently, claims 1-4, and 6-21 are pending in the instant application. Claims 17 and 19 are withdrawn from consideration as being directed to non-elected species. Accordingly, claims 1-4, 6-16, 18, and 20-21 are examined herein. The elected species being considered are Clostridium, Clostridium innocuum, and type IV fimbrae, depending on the limitations for each claim. All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections are newly applied or reiterated. They constitute the complete set being presently applied to the instant Application. Response to Applicant's arguments follow, where applicable. This action is NON-FINAL.
Claim Rejections - 35 USC § 103
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Chia (Chia et al; Clinical Microbiology and Infection, vol 24, 2018, pages 1195-1199) and Hung (Hung et al; Anaerobe, vol 30, 2014, pages 24-26) in view of Lee (Lee et al; Ann Lab Med, vol 36; 2016, pages 387-389), and further in view of Forbes (Forbes et al; Inflamm Bowel Dis, vol 22, 2016, pages 817-825) and Neut (Neut et al; The American Journal of Gastroenterology, vol 97, 2002, pages 939-946).
Chia teaches analysis of Clostridium innocuum, resistant to vancomycin, in antibiotic associated diarrhea (AAD) patients. Chia teaches that patients with AAD caused by C. innocuum had diarrhea and severe colitis (see abstract). Chia teaches that 16S rRNA gene sequence (gene sequencing) was capable of detecting clostridium species (see last paragraph page 1199). Additionally, Hung teaches pathogen analysis of a patient with initial C. difficile associated diarrhea, who developed further bacteremia following vancomycin treatment. Hung teaches PCR analysis of the triosephosphate isomerase gene and sequencing to detect C. innocuum (see page 25). Hung teaches antibiotics to treat vancomycin resistant C. innocuum infection. Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to treat patients with C. innocuum infection with antibiotics other than vancomycin because Chia and Hung teach that the infection causes diarrhea and colitis. Chia and Hung do not teach treating a subject with Crohn’s disease, however Lee teaches bacterial analysis using 16 S rRNA gene sequencing in patients with inflammatory bowel disease (see abstract). Lee teaches that biopsy tissue of a subject with Crohn’s disease was found to have Clostridium innocuum (see table 1). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date, to have treated patients with C. innocuum infection with an antibiotic other than vancomycin, including patients with Crohn’s disease as taught by Lee, for the benefit of treating the symptoms of C. innocuum infection.
Chia, Hung, and Lee do not teach obtaining a sample from an ileal biopsy, however the presence of bacteria in the ileum and ileal mucosa of patients with Crohn’s disease had been analyzed and established prior to the effective filing date. Neut teaches ileal samples of patients with CD, at 3 months following ileocolectomy, showed the presence of Clostridium, Bifidobacterium, and Bacteroides (see figure 2). Additionally, Forbes teaches the presence of Clostridium and Parabacteroides in mucosal samples from the ileum in patients with Crohn’s disease. Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to include treatment in patients with C. innocuum infection detected in samples from the ileum, in the method of Chia, Hung, and Lee for the obvious benefits of treating the symptoms of C. innocuum infection.
Response to Arguments
The response traverses the rejection with regard to newly added claim 21 and asserts that the references are directed to CD associated diarrhea or colitis, not to CD fibrosis. This argument has been thoroughly reviewed but was not found persuasive because claim 21 only requires an active step of administering a treatment to a subject who has been detected with a presence of a microorganism (Clostridium) in an ileal biopsy or ileal mucosal wash or a cultivated isolate therefrom. The wherein clause directed to CD fibrosis is an intended use limitation and does not distinguish the active steps from the teachings of the prior art. Additionally, it appears to be directed to a property of the presence of the microorganism.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Martinez-Medina (hereinafter referred to as Medina: Martinez-Medina et al; Inflamm Bowel Dis; 2006, vol 12; pages 1136-1145) in view of Fujimori (Fujimori et al; Journal of Gastroenterology and Hepatology, vol 22, 2007; pages 1199-1204).
Medina teaches a method of assaying the biopsies of the ileal mucosa in patients with Crohn’s disease (see whole document). Medina teaches 16S rRNA sequencing revealed that patients with the presence of Clostridium, alone and in the presence of Escherichia was more consistently found in patients with CD. Medina does not teach administering a probiotic, a prebiotic, or a combination of a probiotic and a prebiotic to these patients. However Fujimori teaches that therapy with probiotics and prebiotics was safely and effectively used for the treatment of CD (see abstract, whole document). Therefore it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have administered a probiotic and/or a prebiotic as taught by Fujimori to the patients taught by Medina with a reasonable expectation of success for the obvious benefit of treating disease. The wherein clause directed to CD fibrosis is an intended use limitation and does not distinguish the active steps from the teachings of the prior art. Additionally, it appears to be directed to a property of the presence of the microorganism
Claims 1, 4, 6-8, and 11-14 are rejected under 35 U.S.C. 103 as being unpatentable over Martinez-Medina (hereinafter referred to as Medina: Martinez-Medina et al; Inflamm Bowel Dis; 2006, vol 12; pages 1136-1145) in view of Peyrin-Biroulet (hereafter referred to as Biroulet: Peyrin-Biroulet et al; Gut; 2012; vol 61, pages 78-85) and Fujimori (Fujimori et al; Journal of Gastroenterology and Hepatology, vol 22, 2007; pages 1199-1204).
Medina teaches a method of assaying the biopsies of the ileal mucosa in patients with Crohn’s disease (see abstract, whole document). Medina teaches 16S rRNA sequencing revealed that patients with the presence of Clostridium, alone and in the presence of Escherichia was more consistently found in patients with CD. Medina does not teach detecting bacteria in adipose tissue comprising mesenteric adipose tissue, however Biroulet teaches that bacterial translocation to mesenteric fact occurred in 27% of subjects with Crohn’s disease (see abstract; page 83, cols 1-2 and figure 4). Biroulet teaches that the studies conducted demonstrate that bacterial translocation to mesenteric adipocytes expressing PRMs occurs physiologically at a rate similar to that of mesenteric lymph nodes in both animals models and patients with CD. Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date to have included performing detection of Clostridium in adipose tissue as taught by Biroulet in the patients taught by Medina, because Biroulet teaches that bacterial translocation occurs in patients with CD. Given the teachings of Biroulet, the ordinary artisan would have had a reasonable expectation of success that bacteria found in ileal biopsy or mucosa could be detected in mesenteric adipose tissue of patients with CD with a reasonable expectation of success. Medina and Biroulet do not teach administering a probiotic, a prebiotic, or a combination of a probiotic and a prebiotic to these patients. However Fujimori teaches that therapy with probiotics and prebiotics was safely and effectively used for the treatment of CD (see abstract, whole document). Therefore it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have administered a probiotic and/or a prebiotic as taught by Fujimori to the patients taught by Medina and Biroulet with a reasonable expectation of success for the obvious benefit of treating disease.
Claims 2, 3, 9, 10, 15, 16, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Medina in view of Biroulet and Fujimori as applied to claims 1, 4, 6-8, and 11-14 above, and further in view of Lee.
The teachings of Medina in view of Biroulet and Fujimori is set forth above. Medina, Biroulet, and Fujimori do not teach detecting Clostridium innocuum in patients with CD, however Lee teaches bacterial analysis using 16 S rRNA gene sequencing in patients with inflammatory bowel disease (see abstract). Lee teaches that biopsy tissue of a subject with Crohn’s disease was found to have Clostridium innocuum (see table 1). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date to have included testing for Clostridium innocuum in the method of Medina, Biroulet, and Fujimori because Lee teaches that this particular species has been found in CD.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Medina, in view of Biroulet and Fujimori, further in view of Lee as applied to claim 15 above, and further in view of Bordeleau (Bordeleau et al; J. Bacteriol, March 2015, vol 197, pages 819-832).
The teachings of Medina, Biroulet, Fujimori, and Lee are set forth above. Medina, Biroulet, Fujimori, and Lee do not teach detection of Clostridium by detecting type IV fimbriae, however Bordeleau teaches Clostridium T4P genes pilA1 and pilB1 (type IV fimbriae). Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to substitute the detection of Clostridium innocuum using 16S rRNA or the triphosphate isomerase gene, with T4P genes because it would have been immediately obvious that gene sequences from the bacterial genome could be used to detect a bacteria of interest, with a reasonable expectation of success.
Conclusion
No claims are allowed.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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