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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 on 07/29/2025 has been entered.
DETAILED ACTION
In Applicant’s amendment filed on 29 July 2025, claims 117, 128-129, and 131 are amended, claim 119 is canceled, and claims 137-139 are new. Claims 117-118, 122-126, and 128-139 are pending. Claim 134 remains withdrawn. Claims 117-118, 122-126, 128-133, and 135-139 are under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 29 July 2025 is being considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in claims 117 and 137-139 are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide amended claims providing the sequence identifiers for each of the nucleotide and/or amino acid sequences appearing in claims 117 and 137-139.
Claim Objections
Claim 133 is objected to because of the following informalities: the claim recites the alternative limitation: a mammalian milk source selected from human, bovine, pigs, rabbits, goats, sheep, or camel. The limitation is in improper form because it is terminated with the conjunction “or”. Standard practice for reciting alternatives following the phrase “selected from” has the terminal conjunction be “and”, rather than “or” as the claim presently recites, to emphasize that the listed members are all part of the “group” of alternatives to be selected from. It is suggested to amend the Markush group to change the terminal conjunction “or” to “and” to obviate this objection.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 117-118, 122-126, 128-133, and 135-139 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 117 is unclear if the harvested activated Bifidobacterium cells recited in step (b) are the Bifidobacterium cells that were incubated in step (a), or if the Bifidobacterium cells are harvested from some other source. In other words, it is not clear if the incubating step (a) results in the activated Bifidobacterium cells which are harvested in step (b).
Claims 117 and 137-139 recite the following genes without sequence identifiers: Blon_2331, Blon_2334, Blon_2335, Blon_2336, Blon_2337, Blon_2338, Blon_2339, Blon_2340, Blon_2342, Blon_2343, Blon_2344, Blon_2346, Blon_2347, Blon_2354, Blon_2355, Blon_0042, Blon_R0015, Blon_R0017, Blon_R0021, and Blon_R0022. Without appropriate sequence identifiers, the structures of the claimed genes are indefinite and the metes and bounds of the claimed invention cannot be ascertained.
Claims 118, 122-126, 128-133, and 135-139 are dependent on claim 117, so are indefinite for the same reason.
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 117-118, 122-126, 128-131, and 137-139 are rejected under 35 U.S.C. 103 as being unpatentable over Garrido et al. (Oligosaccharide Binding Proteins from Bifidobacterium longum subsp. infantis Reveal a Preference for Host Glycans, PLoS ONE 6(3): e17315, published March 15, 2011) in view of Garner et al. (US 7858336 B1, published December 2010).
Regarding claims 117, 118, 122-126, 128, and 137-139, Garrido teaches a method of incubating Bifidobacterium longum subsp. infantis under anaerobic conditions in the presence of a human (mammalian) milk oligosaccharide (HMO), including the elected oligosaccharide lacto-N-tetraose (LNT) (Garrido page 11 RNA Extraction para. 1, sentences 1-2). The cells were then harvested in exponential and/or stationary phase, immediately purified by pelleting and resuspending the pelleted cells in 1ml of buffer, and stored in refrigerated/frozen conditions until later use (Garrido page 11 RNA Extraction para. 1 sentence 4). Garrido also teaches that B. infantis possesses many enzymes involved in the transportation and deconstruction of HMO and the metabolism of its constituents, including ABC transporters and glycosyl hydrolases (Garrido Page 2 para. 2 sentences 3-6), and affinity of these transporters and hydrolases include fucose and sialic acid compounds (Garrido Fig. 1 structures with red triangles (fucose) and pink diamonds (sialic acid)). Garrido teaches that the Bifidobacterium longum subsp. infantis increased (upregulated) expression of the gene Blon_2344 when activated by incubation in the presence of LNT, thus also upregulating the resultant mRNA and proteins encoded by said Blon--_2344 gene. (Garrido Fig. 2F).
Garrido does not teach drying the centrifuged Bifidobacterium longum subsp. infantis cells.
Garner teaches preserving cells, including Bifidobacterium longum and Bifidobacterium infantis cells (Garner col. 3 lines 25-27 and col. 4 lines 4-11 and 27-32), by a process of freeze-drying and/or spray drying (Garner Col. 15 lines 23-26). Garner also teaches that the dried cells are included into a carbohydrate preservation matrix comprising lactose, which maintains the native, un-collapsed state of the cells’ proteins and membranes during the preservation and storage process, acting as a cryoprotectant (Garner Col. 16 lines 46-52).
Further regarding claim 117 and 137-139, MPEP §2112(I) states “"[t]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer…[t]hus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable". Here, the up- and/or down-regulation of the recited genes is an inherent result of practicing the method of “activating” the cells as taught by Garrido in view of Garner, as evidenced by Figure 2 of Applicant’s disclosure and Applicant’s specification [0069]. The recited up- and/or down-regulation of the genes are not active steps that are required to be performed, but are instead the inherent result of performing the method as taught by Garrido in view of Garner.
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 dry Garrido’s activated and purified Bifidobacterium longum subsp. infantis cells by using Garner’s freeze or spray drying method. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because freeze drying or spray drying Garrido’s activated and purified Bifidobacterium longum subsp. infantis would improve the survivability of the cells, which Garner teaches dramatically impacts the profitability of the direct-feed microbials (i.e. probiotics) administration (Garner col. 3 lines 25-27 and col. 4 lines 4-11).
Regarding claim 129, Garner teaches that the dried cell powder is diluted in an oil carrier to adjust the concentration of the cells to an appropriate concentration for administration (Garner Col. 15 lines 33-35 and 40-43); thus, Garner teaches a dried cell powder suspended into an oil carrier.
Regarding claim 130, Garner teaches that the preserved bacteria are in concentrations between 1x108 to 5x1012 cfu/g (Garner Col. 15 lines 26-29).
Regarding claim 131, Garner teaches that stabilizers can be added to the dried composition comprising the Bifidobacterium cells, wherein the stabilizers are milk-derived proteins (Garner Col. 20 lines 16-24).
Claims 132-133 and 135 are rejected under 35 U.S.C. 103 as being unpatentable over Garrido in view of Garner as applied to claims 117-118, 122-126, 128-131, and 137-139 above, and further in view of Sprenger et al. (US 8771674 B2, published 08 July 2014)
Garrido and Garner do not teach that the culture of Bifidobacterium longum subsp. infantis further comprises complex oligosaccharides.
Sprenger teaches that adding complex oligosaccharides, including the elected species lacto-N-fucosylpentose I, to a culture media of Bifidobacterium longum subsp. infantis increases its metabolic productivity and overall growth (Sprenger Figs. 1 and 2, Col. 6 ln. 4, Col. 11 lns. 29-32), and that the complex oligosaccharides can be derived from a natural source such as animal milks, or alternatively produced by chemical synthesis (Sprenger Col. 6 lns.10-12 and 22-24). Sprenger also teaches that the lacto-N-fucosylpentose I is a human milk oligosaccharides derived from human milk (Sprenger Col. 2 lns. 34-40).
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 add synthetic or naturally produced complex oligosaccharides such as lacto-N-fucosylpentose I into the activated Bifidobacterium longum subsp. infantis composition of Garrido in view of Garner. One of ordinary skill in the art would have been motivated to do so because adding complex oligosaccharides to the culture of Bifidobacterium longum subsp. infantis would increase the microorganism’s metabolic productivity and overall growth. One of ordinary skill in the art would have had a reasonable expectation of success because Sprenger teaches that complex oligosaccharides increase the metabolic productivity and overall growth of a culture of Bifidobacterium longum subsp. infantis.
Claim 136 is rejected under 35 U.S.C. 103 as being unpatentable over Garrido in view of Garner as applied to claims 117-118, 122-126, 128-131, and 137-139 above, and further evidenced by Sela et al (The Genome Sequence of Bifidobacterium longum subsp. infantis Reveals Adaptations for Milk Utilization within the Infant Microbiome, PNAS, Vol. 105, No. 48 (Dec. 2, 2008), pp. 18964-18969).
Garrido and Garner do not specifically teach that the activated Bifidobacterium longum subsp. infantis culture comprises secondary metabolites.
However, the activated Bifidobacterium longum subsp. infantis culture taught by Garrido inherently comprises secondary metabolites, such as acetate and lactate, as evidenced by Sela who teaches that acetate and lactate are metabolites of human milk oligosaccharide metabolism (Sela Figure 3).
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 that Garrido and Garner’s activated Bifidobacterium longum subsp. infantis cell composition inherently comprises secondary metabolites such as acetate and lactate.
Response to Arguments
Applicant's arguments and the 132 Declarations of Dr. Duar and Dr. Heiss filed 29 July 2025 have been fully considered but they are not persuasive. Regarding Applicant’s arguments that it was not appreciated or expected that activation of Bifidobacterium could survive drying prior to the instant invention (Remarks pg. 10 last para. through pg. 12 para. 4, and the 132 Declarations of Dr. Duar and Dr. Heiss), Garner teaches that freeze drying and/or spray drying a probiotic composition stabilizes and improves the survivability of Bifidobacterium cells, which dramatically impacts the profitability of the direct-feed microbials (i.e. probiotics) administration (Garner col. 3 lines 25-27 and col. 4 lines 4-11). The up-regulation of the recited genes is an inherent result of practicing the method of “activating” the cells as taught by Garrido in view of Garner, as evidenced by Figure 2 of Applicant’s disclosure and Applicant’s specification [0069]. The recited up-regulation of the genes are not active steps that are required to be performed, but are instead the inherent result of performing the method as taught by Garrido in view of Garner. MPEP §2112(I) states “"[t]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer…[t]hus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable". When Garner is combined with the Garrido’s disclosure, one of ordinary skill in the art would reasonably understand that freeze or spray drying the activated Bifidobacterium longum subsp. infantis cells composition of Garrido using the Garner’s freeze/spray drying methods would stabilize and improve the survivability of the Bifidobacterium cells.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander M Duryee whose telephone number is (571)272-9377. The examiner can normally be reached Monday - Friday 9:00 am - 5:00 pm.
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, Louise Humphrey can be reached on (571)-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Alexander M Duryee/Examiner, Art Unit 1657 /LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657