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 .
Response to Amendment
Applicant’s remarks and amendments filed 7/23/2025, in response to the non-final rejection mailed 4/25/2025 are acknowledged and have been fully considered.
Any previous rejection or objection not mentioned herein is withdrawn.
Applicant’s amendment to the claims is acknowledged. This listing of the claims replaces all prior versions and listings of the claims. The previous rejections of the claims under 35 U.S.C. § 112(b) for indefiniteness is herein withdrawn in light of the amendments.
Applicant has submitted a declaration titled “Declaration of Availability and Maintenance of Microorganism” that fulfils the requirements of 37 CFR § 1.801-1.809. The prior rejection of claims 1-3 under 35 U.S.C. § 112(a) for lack of enablement is withdrawn.
Claims 1-3 are pending and have been examined on the merits herein.
Claim Objections
Claims 1 is objected to because of the following informalities:
In claim 1, line 2, the article “a” is missing before “Ligilactobacillus animalis strain”. The claim should be amended to recite “a Ligilactobacillus animalis strain” for clarity.
In claim 1, line 2 recites the phrase “strain been deposited in”. The word “been” is unnecessary and results in improper grammar. It appears that the word should have been removed. The claim should be amended to recite “strain, deposited in”.
Appropriate correction is required.
Claim Rejections – 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-3 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The amended claims recite a “pharmaceutical composition or probiotic formulation”, which comprises two components: 1) the Ligilactobacillus animalis strain of deposit number GDMCC No. 62867, and 2) at least one pharmaceutically acceptable carrier.
The B.R.I. of the term “pharmaceutically acceptable carrier” includes any possible carrier known to the art. Carriers may include a variety of substances, including but not limited to water, alcohols, dextrins, creams, gels, emulsions, liposomes, nanoparticles, coatings, and suspensions. No such examples are provided in the instant application.
There is no description nor mention of a “pharmaceutically acceptable carrier” in the application as filed. The specification does not contain any general or specific description of the carrier, nor does the disclosure provide working examples and/or reduction to practice with specific embodiments that employ a carrier.
Therefore, the disclosure as filed does not provide adequate written description for the claimed composition or formulation that includes the specific strain (GDMCC 62887) and a carrier. Claims 1-3 are rejected under 35 U.S.C. § 112(a).
It is suggested to cancel or remove the new matter in the reply to this Office Action.
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.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more.
Claim 1, as amended, recites a composition comprising a Ligilactobacillus animalis strain having deposit number GDMCC No. 62867 and at least one pharmaceutically acceptable carrier. According to the specification, this corresponds to Ligilactobacillus animalis strain “HHP002”. The broadest reasonable interpretation (BRI) of the claim language encompasses the naturally occurring bacteria strain and any suitable carrier.
Claims 2-3 recite a method for inhibiting expression of pro-inflammatory cytokines in human colon cancer in a subject in need thereof, comprising administering to the subject the composition comprising the Ligilactobacillus animalis strain (GDMCC No. 62867). Because claims 2 and 3 are drawn to a specific application of the nature-based product, but clearly do not attempt to tie up the nature-based product itself, these claims do not require a markedly different characteristics analysis to identify a "product of nature" exception. When viewed as a whole, claims 2 and 3 integrate the judicial exception into a practical application and do not seek to tie up the judicial exception such that others cannot practice it. See the streamlined analysis described in MPEP § 2106.06.
For determining subject matter eligibility of claim 1, drawn to a composition comprising a natural based product, the following analysis was considered, per MPEP § 2106.
Patent Eligibility Analysis Step 1: is the claim to a process, machine, manufacture, or composition of matter? For claim 1, YES, the claim is directed to a composition of matter, the Ligilactobacillus animalis strain having deposit number GDMCC NO.62867. (Step 1: YES).
Patent Eligibility Analysis Step 2A Prong 1: is the claim directed to a law of nature, a natural phenomenon (product of nature) or an abstract idea? Claim 1 recites a composition that comprises a strain of Ligilactobacillus animalis, having a particular deposit identifier, and at least one pharmaceutically acceptable carrier. The broadest reasonable interpretation of the claim language encompasses the naturally occurring bacteria strain in a naturally occurring carrier, e.g. in water. No genetic modifications or other manipulations to the bacteria are disclosed. Therefore the claims recite a judicial exception, a product of nature.
When a claim recites a natural product limitation, the markedly different characteristics (MDC) analysis is used to determine whether the natural product has markedly different characteristics from its natural counterpart (see MPEP 2106.04(c)). MPEP § 2106.04(c) explains “Where the claim is to a nature-based product produced by combining multiple components, the markedly different characteristics analysis should be applied to the resultant nature-based combination, rather than its component parts.”
In this case, the closest naturally occurring counterpart is the Ligilactobacillus animalis strain (HHP002) in nature. The isolated and deposited bacterial strain is identical to the naturally occurring strain because the act of isolation does not change a microbial strain; it merely obtains prior naturally-occurring bacteria in a way that allows isolation to a pure colony from the mixture of strains present in nature. No manipulations or changes to the bacteria are disclosed in the instant application. The claimed composition or probiotic formulation including the bacterial strain and a carrier encompasses naturally occurring carriers of the bacteria, such as the natural bacteria in water or a similar suspension.
The second step in the MDC analysis is to identify appropriate characteristics to compare. The appropriate characteristics for analysis can be expressed as the natural product’s structure, function, and/or other properties, and are evaluated on a case-by-case basis. In this case, the appropriate characteristics to compare the bacteria to are the functional properties, including any inherent properties of the strain. No structural properties of the claimed bacteria strain or provided. No information such as sequence data, source of the isolation, or physical properties are recited. The specification describes a variety of functional properties of the claimed L. animalis strain, including a property of suppressing expression of pro-inflammatory cytokines when applied to cultured human colon cancer cells ([0025]-[0034]; [0041]); and properties related to acid resistance and choline (a bile salt) resistance ([0043]-[0050]).
The final step in the markedly different characteristics analysis is to compare the characteristics of the claimed nature-based product to its naturally-occurring counterpart in its natural state, in order to determine whether the characteristics of the claimed product are markedly different. The courts have emphasized that to show a marked difference, a characteristic must be changed as compared to nature, and cannot be an inherent or innate characteristic of the naturally-occurring counterpart or an incidental change in a characteristic of the naturally occurring counterpart. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. Thus, in order to be markedly different, the inventor must have caused the claimed product to possess at least one characteristic that is different from that of the counterpart (MPEP § 2016.04(c).II.C.). If there is no change in any characteristic, the claimed product lacks markedly different characteristics, and is a product of nature exception.
In order to evaluate the functional properties and inherent characteristics of the claimed bacteria strain, the relevant prior references (of record) discussed below were consulted.
Boll et al. (“Ligilactobacillus animalis 506 Protects the Intestinal Barrier from the Damaging Effects of Enteric Pathogens and Deoxynivalenol.” Animals: an open access journal from MDPI vol. 14,2 269. Published Jan. 15, 2024), provided herein as evidence pertaining to properties of naturally occurring L. animalis bacterium, teaches L. animalis strain 506, a probiotic lactic acid-producing bacterial strain that is used in commercial products to support the health and performance of cattle (Summary). Boll discloses studies on the impact of L. animalis strain 506 on gut barrier integrity and regulation of inflammation in vitro using intestinal epithelial cell lines, including using HT29 cell lines (Abstract; Methods), the same cancer cell line as in the instant application. In a cytokine release assay, HT29 cells incubated with the probiotic L. animalis strain had decreased expression of the cytokine IL-8 upon exposure to inflammation-inducing pathogenic bacteria (Figure 2, page 6).
Lee et al. (“Antimicrobial activity of dominant Ligilactobacillus animalis strains in healthy canine feces and their probiotic potential.” FEMS microbiology letters vol. 369,1; 2022) teaches various naturally-occurring strains of Ligilactobacillus animalis, that were identified as the dominant lactic acid bacterium in dog feces, which display various inhibitory effects against pathogenic and enteropathogenic bacteria (Abstract; Table 1). Lee et al. demonstrates that natural strains of L. animalis exhibit tolerance to acidic conditions (Table 1) and resistance to bile salts (Table 2) (Page 2, left column).
Thus, the evidence in the art suggests that the effect on cytokine inhibit and resistance to acids and bile salts (such as choline) are natural properties of the bacteria, as they exist in nature.
The combination of the bacteria strain and a carrier does not result in any markedly different characteristics to the bacteria itself. This merely affects the media (broadly the suspension or encapsulation) of the natural product. The natural product itself is not changed by the media (e.g. carrier) in which it is stored or administered.
To show a marked difference, a characteristic must be changed as compared to nature, and cannot be an inherent or innate characteristic of the naturally occurring counterpart or an incidental change in a characteristic of the naturally occurring counterpart (see MPEP 2106.04 (C)(II)(c)). There is no indication in the record that isolation and use of the claimed strain in a composition or formulation results in a marked difference in structure, function, or other properties compared to its natural counterpart, the claimed strain is a product of nature exception (claim 1, Step 2A, Prong 1: YES).
Patent Eligibility Analysis Step 2A Prong 2: Step 2A, prong 2 asks: does the claim recite additional elements that integrate the judicial exception into a practical application?
This judicial exception is not integrated into a practical application because the claims do not recite any directed application or practical use of the claimed product of nature. Claim 1 is drawn to a composition (or formulation) of the bacteria strain and a carrier. The B.R.I. of the claim encompasses naturally occurring carriers of the bacteria, such as the natural bacteria in water or a similar suspension. However, such the providing of a carrier with the bacterial strain is not a practical application of the naturally-occurring product. The claim as a whole does not integrate the exception into a practical application (claim 1: Step 2A, Prong 2: NO).
Patent Eligibility Analysis Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
Step 2B involves evaluating whether the claims recite additional elements that amount to significantly more than the judicial exception. As discussed above, the claim recites that the natural product, the bacterial strain, is provided with “least one pharmaceutically acceptable carrier”, wherein the B.R.I. of the carrier encompasses naturally occurring carriers of the bacteria, such as water or a similar suspension.
Generally, adjustments or optimization of a concentration of natural product does not result in any particular transformation of the ineligible natural product, nor does such adjustment of concentration constitute an inventive concept. Providing of a carrier, broadly encompassing water and similar naturally-occurring substances, in order to deliver a particular microorganisms does not result in significantly more than the ineligible natural product.
Additionally, the providing of excipients as carriers, including saccharides such as dextrin, is well-known, recognized and conventional in the art when producing pharmaceutical preparations for oral delivery, as evidenced from Alvani and Tester ("Use of carbohydrates, including dextrins, for oral delivery." Starch‐Stärke 63, no. 7 (2011): 424-431).
Alvani and Tester is a review article that describes how carbohydrates are used extensively in the pharmaceutical sector as excipients to facilitate packaging and delivery of drugs in formats include tablets, capsules, liquids, suspensions, gels, inhalation products and strips (Abstract). Alvani and Tester teaches that dextrins benefit from a safe history of usage with a positive health profile, and describes many such dextrins (Abstract, Table 1).
Alvani and Tester teaches that dextrins are water soluble, hydrolytic products of starches, used widely as food and pharmaceutical ingredients to provide dilution, structure, viscosity and calories and they are generally regarded as safe (GRAS) (page 424, left col). The polymers described in Alvani and Tester include natural polymers and natural products of fermentation such as cyclodextrins (CDs)(see pages 425-426).
Alvani and Tester describe many commercially available and well-known polymer and dextrin products for use as drug carriers (see Tables 3 and 4). The reference also describes the advantages and disadvantages of the different saccharide excipients and teaches that the selection and providing of such carriers is common in the art (see the descriptions on pages 429-430).
Additionally, the providing of a probiotic bacteria with a suitable carrier, such as a dextrin or similar carbohydrate is taught at least in “Cevallos et al.”, US PGPub 20140093613; “Shimoni et al.”, US PGPub 20100189767; “Berry et al.” (US Pat No. 11,607,432). Thus, it is evident that the providing of the natural product (i.e. the bacterial strain) with a carrier, which includes liquid solutions such as water and/or excipients such as dextrins, does not amount to an inventive concept such that the claim as a whole amounts to significantly more than the judicial exception.
Additionally, a combination of a natural bacteria strain with a suitable carrier, recited generally, does not practically transform the natural product suspended therein. Further, the use of excipients for drug delivery represents well-known, recognized and conventional activities, as described above. Accordingly, claim 1 as a whole does not include additional elements that are sufficient to amount to significantly more than the judicial exception (claim 1: Step 2B: NO).
Thus, claim 1 is not patent eligible and is rejected under 35 U.S.C. § 101.
Response to Arguments
Applicant's arguments filed 7/23/2025, on pages 5-7 regarding the rejection of claim 1 under 35 U.S.C. § 101 has been fully considered but they are not persuasive.
The Applicant’s main argument pertains to the amendment of the claim to recite a “at least one pharmaceutically acceptable carrier”. The argument that the inclusion of the pharmaceutically acceptable carrier with the natural product does not occur naturally has been considered but is not found persuasive. The full breadth of the carrier encompasses water and alcohols that are naturally occurring and bacteria are typically found in an aqueous solution. Further, even if one was to consider the carrier to require an excipient such as a dextrin, which also includes naturally-occurring carbohydrates, the inclusion of a bacteria strain with such a carrier would be considered well-known in the art and this cannot represent an inventive concept.
These are conventional means in the art which are known for reconstituting bacteria, for storing the organism, and for delivery to the subject to be treated.
Additionally, the argument that the composition has an unexpected and beneficial function is not persuasive as the recitation or discovery of an inherent property of a natural product does not result in a markedly different characteristic than that of the natural product counterpart (and which thus also is presumed to have the beneficial property). See MPEP § 2106.04(b).I, which describes that: “[t]he courts have identified the following concepts and products as examples of laws of nature or natural phenomena… ii. qualities of bacteria such as their ability to create a state of inhibition or non-inhibition in other bacteria, Funk Bros., 333 U.S. at 130, 76 USPQ at 281”. The instant claim 1 is reciting similar naturally occurring properties of bacteria as explained therein.
Thus, the rejection of claim 1 under 35 U.S.C. § 101 is maintained, and modified above, as necessitated by Applicant’s amendment to the claim.
Conclusion
No claims are 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 ANDREW TERRY MOEHLMAN whose telephone number is (571)270-0990. The examiner can normally be reached M-F 9am-5pm EST.
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ANDREW T MOEHLMANExaminer, Art Unit 1655
/TERRY A MCKELVEY/Supervisory Patent Examiner, Art Unit 1655