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The Office action mailed on 07/15/2026 is withdrawn in order to apply the following rejections.
Withdrawn Rejections:
Applicant's amendments and arguments filed on 05/26/2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below is herein withdrawn.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Claims 16-17, 22-24 are pending and under examination.
Priority
Acknowledge is made that this application is national stage of international patent application PCT/KR2023/000838, filed on 01/18/2023; which claims priority from Korean
patent application KR10-2023-0006807, filed on 01/17/2023; and KR10-2022-0008554,
filed on 01/20/2022.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 16-17, 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over Goodman et al. (US20200254028) and Ballok et al. (US20220296654) in view of Kelly et al. (US20150071957).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Goodman et al. teaches compositions related to EVs useful as therapeutic agents (abstract). In certain aspects, provided herein are pharmaceutical compositions comprising bacterial extracellular vesicles (EVs) useful for the treatment and/or prevention of disease (e.g., cancer, autoimmune disease, inflammatory disease, metabolic disease), as well as methods of making and/or identifying such EVs, and methods of using such pharmaceutical compositions (e.g., for the treatment of cancers, autoimmune diseases, inflammatory diseases, metabolic diseases, either alone or in combination with other therapeutics). In some embodiments, the pharmaceutical compositions comprise both EVs and whole bacteria (e.g., live bacteria, killed bacteria, attenuated bacteria). In certain embodiments, provided herein are pharmaceutical compositions comprising bacteria in the absence of EVs. In some embodiments, the pharmaceutical compositions comprise EVs in the absence of bacteria. In some embodiments, the pharmaceutical compositions comprise EVs and/or bacteria from one or more of the bacteria strains or species listed in Table 1 and/or Table 2 ([0002]). In one embodiment, the bacteria strains is Roseburia intestinalis (page 20, [0080], Table 1). EVs are 20-250 nm in diameter ([0100]). In some embodiments, the methods and compositions described herein relate to the treatment or prevention a disease or disorder associated a pathological immune response, such as an autoimmune disease, an allergic reaction and/or an inflammatory disease. In some embodiments, the disease or disorder is an inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) ([0192]). Several major forms of inflammatory bowel diseases are known, with Crohn's disease (regional bowel disease, e.g., inactive and active forms) and ulcerative colitis (e.g., inactive and active forms) the most common of these disorders ([0199]).
Ballok et al. teaches methods and pharmaceutical compositions related to processed microbial extracellular vesicles (pmEVs) that can be useful as therapeutic agents (abstract). As disclosed herein, certain types of microbial extracellular vesicles (mEVs), such as processed microbial extracellular vesicles (pmEVs) obtained from microbes (such as bacteria) have therapeutic effects and are useful for the treatment and/or prevention of disease and/or health disorders ([0002]). n certain aspects, provided herein are pharmaceutical compositions comprising mEVs (such as pmEVs) useful for the treatment and/or prevention of a disease or a health disorder (e.g., adverse health disorders) (e.g., a cancer, an autoimmune disease, an inflammatory disease, a dysbiosis, or a metabolic disease), as well as methods of making and/or identifying such mEVs, and methods of using such pharmaceutical compositions (e.g., for the treatment of a cancer, an autoimmune disease, an inflammatory disease, a dysbiosis, or a metabolic disease, either alone or in combination with other therapeutics). In some embodiments, the pharmaceutical compositions comprise both mEVs and whole microbes from which they were obtained, such as bacteria, (e.g., live bacteria, killed bacteria, attenuated bacteria). In some embodiments, the pharmaceutical compositions comprise mEVs in the absence of microbes from which they were obtained, such as bacteria (e.g., over about 95% (or over about 99%) of the microbe-sourced content of the pharmaceutical composition comprises mEVs) ([0011]). Pharmaceutical compositions containing mEVs (such pmEVs) can provide potency comparable to or greater than pharmaceutical compositions that contain the whole microbes from which the mEVs were obtained. For example, at the same dose of mEVs (e.g., based on particle count or protein content), a pharmaceutical composition containing mEVs can provide potency comparable to or greater than a comparable pharmaceutical composition that contains whole microbes of the same bacterial strain from which the mEVs were obtained. Such mEV containing pharmaceutical compositions can allow the administration of higher doses and elicit a comparable or greater (e.g., more effective) response than observed with a comparable pharmaceutical composition that contains whole microbes of the same bacterial strain from which the mEVs were obtained. As a further example, at the same dose (e.g., based on particle count or protein content), a pharmaceutical composition containing mEVs may contain less microbially-derived material (based on particle count or protein content), as compared to a pharmaceutical composition that contains the whole microbes of the same bacterial strain from which the mEVs were obtained, while providing an equivalent or greater therapeutic benefit to the subject receiving such pharmaceutical composition ([0077-0078]). In one embodiment, the bacteria strains is Roseburia intestinalis (page 25, [0195]). In some embodiments, the methods and pharmaceutical compositions described herein relate to the treatment or prevention of a disease or disorder associated a pathological immune response, such as an autoimmune disease, an allergic reaction and/or an inflammatory disease. In some embodiments, the disease or disorder is an inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis). In some embodiments, the disease or disorder is psoriasis. In some embodiments, the disease or disorder is atopic dermatitis ([0320]). In exemplary embodiments, pharmaceutical compositions useful for treatment of disorders associated with a dysbiosis stimulate secretion of one or more anti-inflammatory cytokines by host immune cells. Anti-inflammatory cytokines include, but are not limited to, IL-10, IL-13, IL-9, IL-4, IL-5, TGFβ, and combinations thereof. In other exemplary embodiments, pharmaceutical compositions useful for treatment of disorders associated with a dysbiosis that decrease (e.g., inhibit) secretion of one or more pro-inflammatory cytokines by host immune cells. Pro-inflammatory cytokines include, but are not limited to, IFNγ, IL-12p70, IL-1α, IL-6, IL-8, MCP1, MIP1α, MIP1β, TNFα, and combinations thereof. Other exemplary cytokines are known in the art and are described herein ([0367]).
Kelly et al. teaches A reduction in inflammation in a subject can be determined by determining the levels of pro-inflammatory cytokines and chemokines in tissue, serum and/or faecal samples in a subject before, and after, the Roseburia flagellin, and/or the polypeptide Fla (such as FlaA1 or FlaA2), and/or the polynucleotide sequence encoding said Roseburia flagellin and/or the polypeptide Fla (such as FlaA1 or FlaA2), and/or the vector comprising said polynucleotide sequence, and/or the host cell comprising said vector, and/or the host cell comprising said polynucleotide sequence, and/or Roseburia (such as the bacterial species Roseburia hominis, or the bacterial species Roseburia intestinalis), is administered to the subject. (0181]). Thus, in one aspect, the Roseburia flagellin, and/or the polypeptide Fla (such as FlaA1 or FlaA2), and/or the polynucleotide sequence encoding said Roseburia flagellin and/or said polypeptide Fla (such as FlaA1 or FlaA2), and/or the vector comprising said polynucleotide sequence, and/or the host cell comprising said vector, and/or the host cell comprising said polynucleotide sequence, and/or Roseburia (such as the bacterial species Roseburia hominis, or the bacterial species Roseburia intestinalis), is for use in treating coeliac disease and Inflammatory Bowel Diseases such as Crohn's disease and ulcerative colitis ([0209]). In one embodiment, the expression level of one or more pro-inflammatory genes is decreased such that the level is at least 10%, 20%, 30%, 40% or 50% lower when compared to the level in the subject before the Roseburia flagellin, and/or the polypeptide Fla (such as FlaA1 or FlaA2), and/or the polynucleotide sequence encoding said Roseburia flagellin and/or said polypeptide Fla (such as FlaA1 or FlaA2), and/or the vector comprising said polynucleotide sequence, and/or the host cell comprising said vector, and/or the host cell comprising said polynucleotide sequence, and/or Roseburia (such as the bacterial species Roseburia hominis, or the bacterial species Roseburia intestinalis), is administered to the subject ([0251]).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02)
The difference between the instant application and Goodman et al. is that Goodman et al. does not specific teach Roseburia intestinalis for treating inflammatory bowel disease. The deficiency of Goodman et al. is cured by the teaching of Ballok et al. and Kelly et al.
Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce the instant invention under guidance of Ballok et al. and Kelly et al.
Goodman et al. teaches a method of treating a list of diseases including inflammatory bowel disease by administering a pharmaceutical composition comprising extracellular vesicles (EVs) from a list of bacterial species including Roseburia intestinalis, the broad teaching from Goodman et al. alone is not specific enough for teaching extracellular vesicles (EVs) of Roseburia intestinalis to treat inflammatory bowel disease.
Under guidance from Ballok et al. teaching a pharmaceutical composition containing mEVs (extracellular vesicles) may contain less microbially-derived material (based on particle count or protein content), as compared to a pharmaceutical composition that contains the whole microbes of the same bacterial strain from which the mEVs were obtained, while providing an equivalent or greater therapeutic benefit to the subject receiving such pharmaceutical composition. This suggest to one artisan in the art that extracellular vesicles and bacterial species from which the extracellular vesicles were obtained have the same therapeutic benefit. Under further guidance from Kelly et al. teaching bacterial species Roseburia intestinalis for use in treating coeliac disease and Inflammatory Bowel Diseases such as Crohn's disease and ulcerative colitis, one artisan in the art would have reasonable expectation of success to treat Inflammatory Bowel Diseases such as Crohn's disease and ulcerative colitis with extracellular vesicles of Roseburia intestinalis.
Regarding claims 16 and 24, prior art teaches a method of treating Inflammatory Bowel Diseases such as Crohn's disease and ulcerative colitis by administering a pharmaceutical composition comprising extracellular vesicles of Roseburia intestinalis. Since prior art teaches treating disease, extracellular vesicles of Roseburia intestinalis must be at effective amount for treating disease.
Regarding claim 17, Goodman et al. teaches EVs at 20-250 nm in diameter.
Regarding claim 22, Goodman et al. teaches Crohn's disease or ulcerative colitis.
Regarding claim 23, since prior art teaches a method of treating Inflammatory Bowel Diseases, and Kelly et al. teaches a reduction in inflammation in a subject can be determined by determining the levels of pro-inflammatory cytokines; and the expression level of one or more pro-inflammatory genes (producing pro-inflammatory cytokines) is decreased after treatment, it is reasonable to conclude that treatment would result in inhibiting inflammatory cytokine production. In summary, although the reference is silent about all the functional properties instantly claimed, it does not appear that the claim language or limitations result in a manipulative difference in the method steps when compared to the prior art disclosure. See Bristol-Myers Squibb Company v. Ben Venue Laboratories, 58 USPQ2d 1508 (CAFC 2001). “It is a general rule that merely discovering and claiming a new benefit of an old process cannot render the process again patentable.” In re Woodruff, 16 USPQ2d 1934, 1936 (Fed. Cir. 1990). Granting a patent on the discovery of an unknown but inherent function would remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art. In re Baxter Travenol Labs, 21 USPQ2d 1281 (Fed. Cir. 1991). See M.P.E.P. 2145. On this record, it is reasonable to conclude that the same patient is being administered the same active agent by the same mode of administration in the same amount in both the instant claims and the prior art reference. The fact that Applicant may have discovered yet another beneficial effect from the method set forth in the prior art does not mean that they are entitled to receive a patent on that method. Thus, prior art teaches, either expressly or inherently implied, each and every limitation of the instant claims. it remains the Examiner's position that the instantly claimed method is obvious.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
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 ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Argument:
Applicants argue that there is no teaching of amended claim.
In response to this argument: this is not persuasive. The new ground of 103 rejection teaches each limitation of applicant’s amended claimed invention expressly or inherently.
MPEP 2141 III states: “The proper analysis is whether the claimed invention would have been obvious to one of ordinary skill in the art after consideration of all the facts.” Respectfully, after weighing all the evidence, the Examiner has reached a determination that the instant claims are not patentable in view of the preponderance of evidence and consideration of all the facts which is more convincing than the evidence which has been offered in opposition to it.
Conclusion
No claim is allowed.
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 JIANFENG SONG. Ph.D. whose telephone number is (571)270-1978. The examiner can normally be reached M-F 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached at (571)272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JIANFENG SONG/Primary Examiner, Art Unit 1613
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