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 .
Claim Status
Claims 1 and 3-15 are pending and have been examined on the merits.
Drawings
RE: Objection to the drawings
The minor informalities in the drawings have been corrected. Thus, the objection to the drawings has been withdrawn.
Claim Interpretation
The limitation “wherein the bile acid conjugated is microbially conjugated” is interpreted to refer to bile acids conjugated with phenylalanine, tyrosine, or leucine. This interpretation is based on these three amino acids being the only amino acids found by applicant to be microbially conjugated (i.e., other amino acids microbially conjugated to bile acids were not detected) that are not glycine or taurine.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
RE: Rejection of claims 1 and 3-15 under 35 U.S.C. 101
Traversal of rejections is based on the combination of the two recited natural products being a non-naturally occurring pharmaceutical composition. Applicant asserts that the Office has not provided any evidence that the combination of a bile acid conjugate and a pharmaceutically acceptable carrier is found in nature. It is also argued that the pharmaceutically acceptable carrier makes the claimed combination different from naturally occurring bile acid conjugates.
The traversal has been fully considered and is found unpersuasive. The two recited components may not occur together in nature but it does not necessarily mean that the claimed pharmaceutical composition is subject matter eligible. MPEP § 2106.04(b)(II) states that “product of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart.” Thus, claims directed to a nature-based product, even when the naturally occurring components are not found in nature together, have to be assessed for markedly different characteristics. The following guidelines must be observed when markedly different characteristics analysis is performed: (a) when the nature-based product is a composition comprising multiple components, markedly different characteristics analysis entails comparing the entire composition to its closest naturally occurring counterpart in its natural state (and when the components are all natural products but are not found in nature together, the closest counterpart may be the individual components); and (b) when the nature-based product is a composition comprising multiple components in which one component is non-natural, markedly different characteristics analysis is only applied to the natural component.
In this case, applicant’s pharmaceutical composition contains two components that are individually found in nature. But since they are not found together naturally, the claimed combination is compared to its closest naturally occurring counterpart – bile acid conjugates naturally produced by microbes. It is noted that applicant initially found the microbially conjugated bile acids that are “conjugated with an amino acid other than glycine or taurine” in germ-free and specific-pathogen-free mice, and later discovered that they are also “common in humans” (par. [0065]), particularly in the gut of humans with inflammatory bowel disease, cystic fibrosis, and in infants (par. [0066]). Review of the specification does not indicate that combining a pharmaceutically acceptable carrier with a microbially conjugated bile acid makes the resulting pharmaceutical composition significantly different from these naturally occurring bile acid conjugates. In other words, the presence of a pharmaceutically acceptable carrier does not provide a meaningful change to the structure, property, or function of a bile acid conjugate that is conjugated by microbes with an amino acid other than glycine or taurine. MPEP § 2106.04(c)(II)(C)(2) states that not all changes in characteristics will rise to the level of a marked difference, i.e., the claimed pharmaceutical composition may be different from naturally occurring bile acid conjugates as it can be administered to a patient, but they are not markedly different. Furthermore, the pharmaceutically acceptable carrier is recited in the claims with high level of generality such that it does not limit the recited natural product for a particular application or use.
Hence, the rejections of record are maintained as proper.
Maintained rejections
Claims 1 and 3-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature and natural phenomenon without significantly more.
The United States Patent and Trademark Office (USPTO) issued a revised guidance for evaluating subject matter eligibility, referred to as “2019 Revised Patent Subject Matter Eligibility Guidance”, which became effective on January 7, 2019 (see 84 Fed. Reg. 50) and updated on October 2019 and July 2024. In the instant application, claims 1 and 3-15 recite a law of nature and natural phenomenon. This judicial exception is not integrated into a practical application, and the claims do not include additional elements that are sufficient to amount to significantly more than said judicial exception as explained below:
Subject Matter Eligibility Guidance
A three-step inquiry has been established to determine subject matter eligibility under 35 U.S.C. 101, in accordance with MPEP 2106:
Step (1). Is the claim directed to a process, machine, manufacture, or composition of matter?
Step (2A). Is the claim directed to a law of nature, natural phenomenon (product of nature), or an abstract idea?
Prong 1 – Does the claim recite a law of nature, natural phenomenon, or an abstract idea?
Prong 2 – If the claim recites a judicial exception, does it recite additional elements that integrate the judicial exception into a practical application? Limitations that are indicative of integration into a practical application include:
Improvements to the functioning of a computer, or to any other technology or technical field. See MPEP 2106.05(a)
Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. See Vanda Memo
Applying the judicial exception with, or by use of, a particular machine. See MPEP 2106.05(b)
Effecting a transformation or reduction of a particular article to a different state or thing. See MPEP 2106.05(c)
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception. See MPEP 2106.05(e) and Vanda Memo.
Step (2B). If the recited judicial exception is not integrated into a practical application, does the claim recite additional elements that amount to significantly different than the judicial exception such that they provide an inventive concept? This step includes evaluation of the same considerations under Step (2A), Prong 2, as well as two additional considerations:
Adding a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field, which is indicative that an inventive concept may be present; and
Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, which is indicative that an inventive concept may not be present.
Analysis in View of the Interim Guidance
The answer to Step (1) is “yes” since the claims are directed to a composition of matter, which is a statutory category.
The answer to Step (2A) is “yes” because the claimed pharmaceutical composition is directed to a law of nature and natural phenomenon, specifically natural products.
Prong 1: Claim 1 recites that the pharmaceutical composition comprises “a bile acid conjugate and a pharmaceutically acceptable carrier”. The bile acid conjugate is required to be conjugated with an amino acid other than glycine or taurine and “microbially conjugated”, which are bile acids conjugated with phenylalanine, tyrosine, or leucine found not only in mice but also in humans with inflammatory bowel disease and cystic fibrosis as well as in infants (par. [0061], [0066]), and is therefore a natural product. Similarly, the pharmaceutically acceptable carrier encompasses naturally occurring substances like water and sodium chloride (par. [0048], Specification). Thus, the pharmaceutical composition is a mixture of natural products and its closest naturally occurring counterpart is the conjugated bile acid-containing metabolites in the gut. There is no evidence that the claimed combination is significantly different in structure, property, and/or function from naturally occurring microbially conjugated bile acids as they occur in nature.
Some dependent claims further specify that “the pharmaceutically acceptable carrier comprises an excipient, diluent, preservative, solubilizer, emulsifier, adjuvant, and/or vehicle”, but this limitation also does not result in markedly different characteristics. Another dependent claim requires that the composition additionally comprises Clostridia microbes, which are bacteria found in nature and adding it to the pharmaceutical composition does not also lead to markedly different characteristics.
Prong 2: There are no additional elements that integrate the recited judicial exception into a practical application. The presence of pharmaceutically acceptable carrier (and Clostridia microbes) does not cause a transformation or transformation of the microbially conjugated bile acids, nor does it limit its application to a particular field of use.
The answer to Step (2B) is “no”. Formulating bile acid conjugates as a pharmaceutical composition is well-understood and conventional in the field. For example, Tirosh et al. (US 2016/0120880 A1; previously cited) teaches a pharmaceutical composition comprising a conjugate of a bile acid with at least one basic amino acid, wherein the basic amino acid is selected from arginine, lysine, histidine, and ornithine in combination with a pharmaceutically acceptable carrier (par. [0080], [0085], [0185]).
Hence, claims 1 and 3-15 are directed to a judicial exception and do not qualify as eligible subject matter under 35 U.S.C. § 101.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
RE: Nonstatutory double patenting rejections
No arguments regarding the double patenting rejections were submitted. Accordingly, the rejections are maintained.
Maintained rejections
Claims 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,980,645.
The U.S. patent is directed to a method of treating a subject having inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), cystic fibrosis (CF), liver cancer, colorectal cancer, diabetes, non-alcoholic fatty liver disease or atherosclerosis. The method comprises administering to the subject an effective amount of a pharmaceutical composition comprising one or more microbially conjugated bile acids that modulate levels of a bile acid conjugate in the subject. The one or more microbially conjugated bile acids are specified to be conjugated with amino acids other than glycine or taurine.
Although the claims at issue are not identical, they are not patentably distinct from each other because the pharmaceutical composition used in the disclosed method is the same as the pharmaceutical composition in the claims of the instant application.
Conclusion
No claim is allowed.
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 MICHELLE F PAGUIO FRISING whose telephone number is (571)272-6224. The examiner can normally be reached Monday-Friday, 8:00 a.m. - 4:00 p.m..
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, Melenie L. 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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/Michelle F. Paguio Frising/Primary Examiner, Art Unit 1651