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 .
Election/Restrictions
Applicant’s election of species of claims amendment filed 1/12/2024, in the reply filed on 1/14/2026 is acknowledged.
Upon reconsideration, the election of species requirement as set forth in the Office action mailed on 11/19/2025, is hereby withdrawn and nonelected species are hereby rejoined and fully examined for patentability under 37 CFR 1.104. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims status
The preliminary amendments filed 1/12/2024 is entered. Claims 1-12 are pending and under examination.
Priority
Acknowledgment is made of applicant's claim for foreign priority. However, the foreign priority document is not translated to English; therefore, the examiner cannot determine if it discloses the presently claimed invention. Therefore, the effective filing date is 07/15/2022, which is the PCT filing date.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1/12/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being
considered by the examiner.
Claim Objections
Claim 7 objected to because of the following informalities: group “(II)” designation is an unconventional and potentially confusing naming of the group of prebiotics. Appropriate correction is required.
Claim 9 is objected to because of the following informalities: missing ending punctuation (i.e. period). Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-12 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 5 has a first recitation of mixture (“said mixture”) and a second recitation of mixture (“a mixture thereof”). The first recitation of mixture (“said mixture”) is in reference to the recitation of mixture in parent claim 1, but it is unclear what the boundaries of this mixture is and the specification does not provide a definite definition for “mixture” for this claim. The mixture in claim 1 is written as an option for the limitation that recites “said strain of bacteria belongs to the species Lactobacillus paracasei and is selected from the group consisting of: Lactobacillus paracasei DG® CNCM 1-1572, Lactobacillus paracasei LPC-SOl DSM 26760, and a mixture thereof”. The plain meaning for the option for “mixture thereof” would therefore be the strain of bacteria is a mix of both Lactobacillus paracasei DG® CNCM 1-1572 and Lactobacillus paracasei LPC-SOl DSM 26760 at some ratio. However, the first recitation of mixture (“said mixture”) in claim 5 is recited to consist of “a strain of bacteria belonging to the species Lactobacillus paracasei and is selected from the group consisting of: Lactobacillus paracasei DG® CNCM 1-1572, Lactobacillus paracasei LPC-SOl DSM 26760, and a mixture thereof; and at least one food grade or pharmaceutical grade additive and/or excipient” implying that the previously claimed mixture in claim 1 contained a mixture of bacteria and more additives/excipients. Therefore, it is inconsistent with the plan meaning of “mixture” as one would understand it in this context and the full scope of the mixture is unclear.
This unclear scope and definition of “mixture” renders the second recitation of mixture (“a mixture thereof”) indefinite, as it is unclear whether the mixture could contain all the components taught in mixtures in the specification (page 8) or if it is just a mix of two bacteria strains.
Claim 6-7, which depend on claim 5, recites “said mixture” but there are two mixtures in claim 5, and therefore the mixture of claim 6-7 is indefinite because it fails to resolve the indefiniteness of its parent claim and is unclear which mixture it is referring to and what the scope of each mixture is.
Claims 10 and 12 depend on indefinite claims and fail to resolve the indefiniteness of the “mixture” term.
Claims 1, 5, and 6 contain the trademark/trade name DG®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the Lactobacillus paracasei strain and, accordingly, the identification/description is indefinite. The examiner recognizes that Lactobacillus paracasei with deposit number CNCM I-1572 alone, without the trademarked DG®, would be sufficiently definite towards describing the strain.
Claims 2-4 and 7-12 depend on claims 1, 5, and 6, so inherit the indefiniteness and fail to resolve the indefiniteness.
Regarding claim 7, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2, 5-7, 10, and 12 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 2 broadens the age range of the subject to one month to less than or equal to 12 months from the claim it depends upon, which recites the subject is in the first four weeks of life.
Claim 5 has a first recitation of mixture (“said mixture”) and a second recitation of mixture (“a mixture thereof”). The first recitation of mixture (“said mixture”) is in reference to the recitation of mixture in parent claim 1, but broadens the scope of the mixture of claim 1 to further include at least one food grade or pharmaceutical grade additive and/or excipient.
Claim 5 recites a mixture that “consists” of a bacteria strain, which is understood to mean the mixture contains a closed list of components, wherein the component is a bacteria strain from the list. However, claim 6, 7, and 10 further broadens what the mixture contains, besides the bacteria strain in the parent claim. Claim 12 depends on claim 5 and therefore incorporates the improper dependent form of claim 5.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-5, 7, 9, 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Vlieger et al (Vlieger, A., et al, Tolerance and safety of Lactobacillus paracasei ssp. paracasei in combination with Bifidobacterium animalis ssp. lactis in a prebiotic-containing infant formula: a randomised controlled trial, British Journal of Nutrition, 102, 869–875; published 03/31/2009) in view of Cremon et al (Cremon, C., et al, Effect of Lactobacillus paracasei CNCM I-1572 on symptoms, gut microbiota, short chain fatty acids, and immune activation in patients with irritable bowel syndrome: A pilot randomized clinical trial ; published 05/2018) and further in view of Navarro-Tapia et al (Navarro-Tapia, E., et al, Probiotic Supplementation during the Perinatal and Infant Period: Effects on gut Dysbiosis and Disease, Nutrients 2020, 12, 2243, published 07/27/2020).
The instant specification defines a “method of treating” to include “the elimination, reduction/decrease or prevention of a pathology or disease and related symptoms or disorders” (page 10, line 6-9).
Vlieger et al teaches a method of treating and/or preventing gastrointestinal related disorders of an inflammatory and/or functional nature in a subject in need thereof with a composition comprising of bacteria strains (Abstract). Vlieger et al teach that the strain of bacteria is a Lactobacillus paracasei strain (Abstract). Vlieger et al teaches that the effect of this treatment was softer stool and increased defecation frequency in the subject, which is a reduction of a related symptom of the claimed disorders, such as intestinal colic, IBS with alternating bowel (also known as IBS-M/Mixed) and IBS with prevalent constipation or constipated bowel (also known as IBS-C/with Constipation) (section Discussion).
Vlieger et al does not explicitly teach the specific Lactobacillus paracasei strains instantly claimed.
Vlieger et al does not explicitly teach the specific disorder.
Vlieger et al does not explicitly teach the subject is a newborn subject in the first four weeks of life.
However, Cremon et al teaches Lactobacillus paracasei DG® CNCM I-1572 has effects on the reduction/decrease or prevention of a pathology or disease and related symptoms or disorders in subjects with IBS. Cremon et al teaches that subjects treated with Lactobacillus paracasei DG® CNCM I-1572 showed reduced presence of a bacteria genus associated with IBS (page 609), and reduced pro-inflammatory cytokine IL-15 levels which is taught to play a primary role in the development of several inflammatory diseases, such as IBS (page 611), arriving at some of the limitations of claim 1.
Vlieger et al in view of Cremon et al does not explicitly teach the subject is a newborn subject in the first four weeks of life.
Vlieger et al does teach the method in newborns starting from at most 7 days of age until 3 months of age (section Subjects and section Trial Design).
However, Navarro-Tapia et al teaches the importance of the perinatal period, which starts at the 20th week of gestation and ends 4 weeks after birth, in establishing lifelong gut microbiota; and that use of probiotics and paraprobiotics as therapeutic tools is attracting great interest, especially in the perinatal period (Abstract), providing motivation for focusing on the specific timeframe in claim 1, arriving at all the limitations of claim 1.
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to substitute the Lactobacillus paracasei strain taught by Vlieger et al with the Lactobacillus paracasei strain taught by Cremon et al in light of the finding that this strain can reduce bacteria and cytokines associated with IBS and gastrointestinal inflammatory diseases. It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to specifically focus on administration during the four weeks after birth during the perinatal phase, taught by Navarro-Tapia et al as critical to the lifelong health of the infant.
Vlieger et al teaches a study that comprised of healthy newborn subjects. In contrast, Cremon et al teaches a study that comprised of adult patients diagnosed with IBS. One skilled in the art, before the effective filing date of the instant application, would be motivated to harness the advantages of the Lactobacillus paracasei strain taught by Cremon et al for newborns with IBS or other related pathologies. One skilled in the art, before the effective filing date of the instant application, would be motivated to administer these beneficial probiotics during a defined period that is critical to the lifelong health of the infant.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success due to the findings of no treatment-related adverse effects for the Lactobacillus paracasei strain and its beneficial mechanisms of action taught by Cremon et al. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success due to the examples supporting probiotic supplementation during the perinatal period taught by Navarro-Tapia et al (reviewed throughout Table 6).
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that a simple substitution of one known element for another to obtain predictable results is obvious. The prior art contained a method that differed from the instant application by the substitution of the Lactobacillus paracasei strain with another Lactobacillus paracasei strain taught in a different prior art. Therefore, the substituted components and their functions were known in the art to serve similar purposes in treating and/or preventing gastro-intestinal disorders of an inflammatory and/or functional nature. One of ordinary skill in the art, before the effective filing date, could have substituted on known element for another, and the results of the substitution would have bene predictable in light of the human-subject trials presented in the prior art. KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), also discloses that if some teaching, suggestion, or motivation in the prior art would lead one skilled in the art before the effective filing date to combine prior art references, then the modification is obvious. The direct teaching by Navarro-Tapia et al regarding the motivation to administer probiotics during the first four weeks of life provides an obvious motivation for focusing on this timeframe.
Claims 2-5 and 11 depend on claim 1. The teachings of the references for claim 1 are described above and incorporated in its entirety for claims 2-5 and 11, and further described below.
Regarding claim 2, Vlieger et al further teaches continuing the method in newborn subjects at 3 months old to 6 months old.
Regarding claim 3, Vlieger et al (section Study formulas) and Cremon et al (section Study design) further teaches the method using viable strains of bacteria. Navarro-Tapia et al further teaches that derivatives of strains of bacteria, such as inactivated strains (also called paraprobiotics) could be useful for infants and vulnerable populations (page 38, paragraph 2).
Regarding claim 5, Vlieger et al further teaches the method further comprises of a mixture of bacteria strains and at least one food grade or pharmaceutical grade additive and/or excipient, as they teach the strain was added to an infant formula mix that contains such additives, called Friso 1 (section Study formulas).
Regarding claim 4, Cremon et al further teach the method wherein the disorder is IBS (Abstract).
Regarding claim 11, Vlieger et al further teaches the method wherein said disorders are selected from the group consisting of: neonatal colic, intestinal colic, chronic enterocolitis or chronic enterocolitis in preterm newborns and necrotizing enterocolitis, as evidenced by the increase in defecation frequency and softer stools (page 873, paragraph 2).
Claim 7 and 12 depend on claim 5, which depends on claim 1. The teachings of the references for claims 1 and 5 are described above and incorporated in its entirety for claims 7 and 12, and further described below.
Regarding claim 7, Vlieger et al further teaches the strain was added to an infant formula mix, called Friso 1, which contains, for example, GOS (galacto-oligosaccharide), zinc, and Vitamins B and D (section Study formulas).
Regarding claim 12, Vlieger et al further teaches the limitations of claim 5 and Vlieger et al further teaches the method wherein said disorders are selected from the group consisting of: neonatal colic, intestinal colic, chronic enterocolitis or chronic enterocolitis in preterm newborns and necrotizing enterocolitis, as described for claim 1, as evidenced by the increase in defecation frequency and softer stools (page 873, paragraph 2).
Claim 9 depends on claim 3, which depends on claim 1. The teachings of the references for claims 1 and 3 are described above and incorporated in its entirety for claim 9, and further described below.
Regarding claim 9, Navarro-Tapia et al further teaches tyndallized probiotics for infants and vulnerable population (page 38, paragraph 2).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to combine components from each of the prior art references in light of the advantages taught. Regarding claims 3 and 9, it would be obvious to one skilled in the art, before the effective filing date of the instant application, that viable bacteria strains can be used in newborns, but the option to use derivatives of the bacteria strains may be considered for highly vulnerable populations. Regarding claims 4 and 11-12, it would be obvious to one skilled in the art, before the effective filing date of the instant application, that the bacteria strains taught by the prior art would be reasonable probiotic candidates for the gastro-intestinal disorders claimed, as the prior art teaches them for use in treating and/or preventing these gastrointestinal disorders. Regarding claims 5 and 7, it would be obvious that these bacterial strains could be formulated with the additives claimed, and would benefit from coformulation with additional components, such as prebiotics, in light of the art teaching the synergy of prebiotic oligosaccharides and beneficial bacteria (Navarro-Tapia et al, page 16).
One skilled in the art, before the effective filing date of the instant application, would be motivated to combine these beneficial elements in known disease models to reduce the risk of adverse effects and treat gastrointestinal disorders in newborns.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success with inactivated bacteria and the additional components in the formulation since these techniques and components are not specifically beneficial to the particular bacteria strains but rather for probiotics in general.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that combining prior art elements according to known methods to yield predictable results is obvious. The prior art includes each element claimed although not necessarily in a single reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference. The use of the particular strain from Cremon et al likely does not preclude the addition of the additives, the use in the claimed disease models, the use of its derivatives, and the use in certain populations, as is relevant to these claims and taught by Vlieger et al and Navarro-Tapia et al. Therefore, one of ordinary skill in the art, before the effective filing date, could have combined the elements and each element would be expected to perform, at least, the same function as it does separately.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Vlieger et al in view of Cremon et al and further in view of Navarro-Tapia et al as applied to claims 1-5, 7, 9, 11-12 above, and further in view of Biffi WO‘458 (Biffi, A., WO2022208458A1, Inactivated strains of bacteria, such as viable but non-culturable bacteria, compositions and use thereof; Effectively filed 04/01/2021 by priority application IT102021000008300).
Claim 6 depends on claim 5, which depends on claim 1. The teachings of the references for claims 5 and 1 are discussed above and incorporated in its entirety for claim 6 and further discussed below.
Vlieger et al teaches the method comprising of a mixture of Lactobacillus paracasei and Bifidobacterium animalis ssp. Lactis in an infant formula (Abstract).
Vlieger et al in view of Cremon et al and further in view of Navarro-Tapia et al do not explicitly teach the instantly claimed strain of Bifidobacterium animalis ssp. Lactis.
However, Biffi WO‘458 teaches the instantly claimed strain Bifidobacterium animalis subsp. Lactis BlIBS01 DSM 33233 in a method of treating intestinal dysbiosis, inflammatory or functional gastrointestinal diseases and diseases caused by pathogenic microorganisms (Abstract and page 9).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that combining two bacteria species, Lactobacillus paracasei ssp. paracasei and Bifidobacterium animalis ssp. lactis is possible and beneficial, in light of Vlieger et at teaching this combination and the art especially recognizing the benefits of mixtures of Lactobacillus and Bifidobacterium (Navarro-Tapia et al, Abstract). It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to choose from the strain provided by Biffi WO’458 as this strain was already disclosed to treat gastrointestinal diseases.
One skilled in the art, before the effective filing date of the instant application, would be motivated to use the combination of two bacteria species known in the art and choose specific strains for the particular desired purpose based on teachings of the prior art about these strains, as both bacteria have different beneficial but compatible effects. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success in the method to treat gastrointestinal diseases as this strain was already disclosed to treat gastrointestinal diseases.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that use of a known technique to improve similar methods or products in the same way is obvious. The combination of bacteria species to improve on formulations with single bacteria species are known techniques used to improve probiotic formulations that can be applied to the relevant probiotic strains taught in the art, to arrive at the claimed invention. Although the prior art teaches the specific bacteria strains in different references, the bacteria strains and its uses are comparable and therefore, could benefit from the same improvement when combined with other probiotic bacteria, and the results would still be reasonably predictable.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Vlieger et al in view of Cremon et al and further in view of Navarro-Tapia et al as applied to claims 1-5, 7, 9, 11-12 above, and further in view of Biffi WO’636 (Biffi, A., et al, WO2021053636A1, Bacterial strains, their compositions and their use for the treatment of gastrointestinal disorders; published 03/25/2021).
Claim 6 depends on claim 5, which depends on claim 1. The teachings of the references for claims 5 and 1 are discussed above and incorporated in its entirety for claim 6 and further discussed below.
Vlieger et al teaches the method comprising of a mixture of Lactobacillus paracasei and Bifidobacterium animalis ssp. Lactis in an infant formula (Abstract).
Vlieger et al in view of Cremon et al and further in view of Navarro-Tapia et al do not explicitly teach the instantly claimed strain of Bifidobacterium animalis ssp. Lactis.
However, Biffi WO‘636 teaches the instantly claimed strain Bifidobacterium breve DSM 33231, Bifidobacterium breve DSM 33232, Bifidobacterium animalis subsp. Lactis DSM 33233, Lactobacillus plantarum DSM 33234, and Bifidobacterium bifidum BbfIBS0l DSM 32708 in methods for the preventive and/or curative treatment of gastrointestinal diseases, disorders or symptoms (page 1, paragraphs 1-3).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that combining two bacteria species of the Lactobacillus and/or Bifidobacterium, is possible and beneficial, in light of Vlieger et at teaching this combination and the art especially recognizing the benefits of mixtures of Lactobacillus and Bifidobacterium species (Navarro-Tapia et al, Abstract). It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to choose from the list of strains provided by Biffi WO’636 as these strains were already disclosed to treat gastrointestinal diseases.
One skilled in the art, before the effective filing date of the instant application, would be motivated to use the combination of two bacteria species known in the art and choose specific strains for the particular desired purpose based on teachings of the prior art about these strains, as both bacteria have different beneficial but compatible effects. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success in the method to treat gastrointestinal diseases as these strains were already disclosed to treat gastrointestinal diseases.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that use of a known technique to improve similar methods or products in the same way is obvious. The combination of bacteria species to improve on formulations with single bacteria species are known techniques used to improve probiotic formulations that can be applied to the relevant probiotic strains taught in the art, to arrive at the claimed invention. Although the prior art teaches the specific bacteria strains in different references, the bacteria strains and its uses are comparable and therefore, could benefit from the same improvement when combined with other probiotic bacteria, and the results would still be reasonably predictable.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Vlieger et al in view of Cremon et al and further in view of Navarro-Tapia et al as applied to claims 1-5, 7, 9, 11-12 above, and further in view of Malfa et al (Malfa, P., et al, IT201900000801A1, Composition including non-viable probiotic bacteria and its use in therapy; published 07/18/2020).
Claim 8 depends on claim 3, which depends on claim 1.
Navarro-Tapia et al further teaches that derivatives of strains of bacteria, such as inactivated strains (also called paraprobiotics) could be useful for infants and vulnerable populations.
Vlieger et al in view of Cremon et al and further in view of Navarro-Tapia et al do not explicitly teach the bacterial strain is gamma irradiated.
However, Malfa et al teaches the bacterial strain is gamma irradiated.
Malfa et al teaches the disadvantages of other methods of bacteria inactivation (section State of the Art) and contrast it to inactivation by gamma rays, which maintain integrity of the bacteria cell wall, which allow it to maintain adhesive properties, which is helpful for remaining at the target site (Description of the invention). Malfa et al teaches this method can be applied to Lactobacillus paracasei (Description of the invention).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that gamma irradiated bacteria strains could be advantageous for probiotic functions over other methods of bacteria inactivation, according to the teachings of Malfa et al, and that although Malfa et al teaches their method with topical administration of the bacteria, the benefits are applicable to the gastrointestinal environment.
One skilled in the art, before the effective filing date of the instant application, would be motivated to utilize gamma irradiation to inactivate probiotic bacteria in light of the potential drawbacks taught for other common methods of bacteria inactivation.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success because this combination of bacteria species is already taught in the art to provide a multi-pronged approach to treatment. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success with gamma irradiated bacteria as it has been taught to be a suitable and perhaps better substitute for heat-inactivated probiotic bacteria or other common methods of inactivation, as it helps retain the ability for the bacteria to adhere to the intestinal wall, where it needs to work, but reduces potential undesired reactions against a live probiotic that may be especially salient in newborn subjects.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that use of a known technique to improve similar methods or products in the same way is obvious. The use of gamma irradiation to improve on probiotics inactivated by other methods are known techniques used to improve probiotic formulations that can be applied to the relevant probiotic strains taught in the art, to arrive at the claimed invention.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Vlieger et al in view of Cremon et al and further in view of Navarro-Tapia et al as applied to claims 1-5, 7, 9, 11-12 above, and further in view of Dilli et al (Dilli, D., et al, The ProPre-Save Study: Effects of Probiotics and Prebiotics Alone or Combined on Necrotizing Enterocolitis in Very Low Birth Weight Infants, J Pediatr 2015;166:545-51; published 03/2015).
Claim 10 depends on claim 7, which depends on claim 5, which depends on claim 1.
Vlieger et al further teaches the strain was added to an infant formula mix, called Friso 1, which contains Vitamins B and D (section Study formula). Vlieger et al further explicitly teaches a prebiotic-containing formula was chosen (section Study formula).
Vlieger et al does not explicitly teach at least one prebiotic is inulin.
However, Dilli et al teaches a synbiotic comprising of inulin and Bifidobacterium lactis (also known as Bifidobacterium animalis subsp. Lactis) for infants to prevent necrotizing enterocolitis (NEC). Dilli et al further teaches inulin as a prebiotic sugar that stimulate the growth and metabolic activity of beneficial bacteria. Dilli et al provides a list of exemplary prebiotic sugars including inulin and galacto-oligosaccharide (Abstract) and therefore they can be understood by one skilled in the art, before the effective filing date, that these prebiotic sugars may be suitable alternatives to choose from depending on its utility to specific bacteria probiotic. Dilli et al further teaches that both normal flora Bifidobacterium and Lactobacillus spp. colonization is delayed in premature infants (Discussion paragraph 1). As such, one would be motivated to also use inulin with Lactobacillus species, arriving at the claimed invention.
In summary, Vlieger et al teaches probiotics Lactobacillus paracasei and Bifidobacterium animalis subsp. Lactis with prebiotic galacto-oligosaccharide while Dilli et al teaches Bifidobacterium animalis subsp. Lactis with prebiotic inulin but teaches inulin and galacto-oligosaccharide as prebiotics (Abstract). It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that the galacto-oligosaccharide could be substituted with inulin as the prebiotic for formulations comprising of Lactobacillus paracasei as both sugars are used to stimulate probiotic growth.
One skilled in the art, before the effective filing date of the instant application, would be motivated to try the inulin as a prebiotic for Lactobacillus paracasei, as Dilli et al teaches that Lactobacillus and Bifidobacterium are two normal bacterial flora (Discussion, paragraph 1), and therefore, are often probiotic candidates administered together, as taught by Vlieger et al. As such, since inulin is shown to work for Bifidobacterium, it would be useful to try this with Lactobacillus to see if inulin can be used for both probiotics, which could be especially useful in probiotic combinations.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success since these common prebiotics are chosen for their ability to be metabolized by many bacterial species.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success is obvious. Dilli et al teaches a finite number of identified predictable potential solutions (i.e. prebiotics) that could be useful with the probiotic bacteria. One skilled in the art, before the effective filing date of the instant application, could have pursued the known potential prebiotics with reasonable expectation of success with the two common species of probiotics.
Double Patenting
Nonstatutory double patenting
The USPTO may not institute a derivation proceeding in the absence of a timely filed petition. The U.S. Patent and Trademark Office normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). The applicant should amend or cancel claims such that the reference and the instant application no longer contain claims directed to the same invention.
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.
U.S. Patent No. US11752179B2:
Claims 1-5, 7, 9, 11-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. US11752179B2 (hereafter referred to as Biffi ‘179) in view of Vlieger et al (Vlieger, A., et al, Tolerance and safety of Lactobacillus paracasei ssp. paracasei in combination with Bifidobacterium animalis ssp. lactis in a prebiotic-containing infant formula: a randomised controlled trial, British Journal of Nutrition, 102, 869–875; published 03/31/2009) and further in view of Cremon et al (Cremon, C., et al, Effect of Lactobacillus paracasei CNCM I-1572 on symptoms, gut microbiota, short chain fatty acids, and immune activation in patients with irritable bowel syndrome: A pilot randomized clinical trial ; published 05/2018) and further in view of Navarro-Tapia et al (Navarro-Tapia, E., et al, Probiotic Supplementation during the Perinatal and Infant Period: Effects on gut Dysbiosis and Disease, Nutrients 2020, 12, 2243, published 07/27/2020). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant specification defines a “method of treating” to include “the elimination, reduction/decrease or prevention of a pathology or disease and related symptoms or disorders” (page 10, line 6-9).
Regarding instant claim 1, Biffi ‘179 claim 1 teaches a method of treating subjects suffering from IBS with Lactobacillus paracasei DG CNCM I-1572. Cremon et al also teaches Lactobacillus paracasei DG CNCM I-1572. Cremon et al teaches Lactobacillus paracasei DG® CNCM I-1572 has effects on the reduction/decrease or prevention of a pathology or disease and related symptoms or disorders in subjects with IBS. Cremon et al teaches that subjects treated with Lactobacillus paracasei DG® CNCM I-1572 showed reduced presence of a bacteria genus associated with IBS (page 609), and reduced pro-inflammatory cytokine IL-15 levels which is taught to play a primary role in the development of several inflammatory diseases, such as IBS (page 611).
Biffi ‘179 does not explicitly teach the subject is a newborn subject in the first four weeks of life.
However, Vlieger et al teaches a method of treating and/or preventing gastrointestinal related disorders of an inflammatory and/or functional nature in a subject in need thereof with a composition comprising of bacteria strains (Abstract). Vlieger et al teach that the strain of bacteria is a Lactobacillus paracasei strain (Abstract). Vlieger et al teaches that the effect of this treatment was softer stool and increased defecation frequency in the subject, which is a reduction of a related symptom of the claimed disorders, such as intestinal colic, IBS with alternating bowel (also known as IBS-M/Mixed) and IBS with prevalent constipation or constipated bowel (also known as IBS-C/with Constipation) (section Discussion).
Vlieger et al does teach the method in newborns starting from at most 7 days of age until 3 months of age (section Subjects and section Trial Design).
Biffi ‘179 claim 1 in view of Vlieger et al and further in view of Cremon et al do not explicitly teach the subject is a newborn subject in the first four weeks of life.
However, Navarro-Tapia et al teaches the importance of the perinatal period, which starts at the 20th week of gestation and ends 4 weeks after birth, in establishing lifelong gut microbiota; and that use of probiotics and paraprobiotics as therapeutic tools is attracting great interest, especially in the perinatal period (Abstract), providing motivation for focusing on the specific timeframe in claim 1, arriving at all the limitations of claim 1.
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to substitute the Lactobacillus paracasei strain taught by Vlieger et al with the Lactobacillus paracasei strain taught by Biffi ‘179 claim 1 and Cremon et al in light of the finding that this strain can reduce bacteria and cytokines associated with IBS and gastrointestinal inflammatory diseases. It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to specifically focus on administration during the four weeks after birth during the perinatal phase, taught by Navarro-Tapia et al as critical to the lifelong health of the infant.
Vlieger et al teaches a study that comprised of healthy newborn subjects. In contrast, Biffi ‘179 claim 1 and Cremon et al teaches subjects suffering from IBS. One skilled in the art, before the effective filing date of the instant application, would be motivated to harness the advantages of the Lactobacillus paracasei strain taught by Biffi ‘179 claim 1 and Cremon et al for newborns with IBS or other related pathologies. One skilled in the art, before the effective filing date of the instant application, would be motivated to administer these beneficial probiotics during a defined period that is critical to the lifelong health of the infant.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success due to the findings of no treatment-related adverse effects for the Lactobacillus paracasei strain and its treatment potential in IBS taught by Biffi ‘179 claim 1 and Cremon et al. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success due to the examples supporting probiotic supplementation during the perinatal period taught by Navarro-Tapia et al (reviewed throughout Table 6).
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that a simple substitution of one known element for another to obtain predictable results is obvious. The prior art contained a method that differed from the instant application by the substitution of the Lactobacillus paracasei strain with another Lactobacillus paracasei strain taught in the copending application and Cremon et al. Therefore, the substituted components and their functions were known in the art to serve similar purposes in treating and/or preventing gastro-intestinal disorders of an inflammatory and/or functional nature. One of ordinary skill in the art, before the effective filing date, could have substituted on known element for another, and the results of the substitution would have bene predictable in light of the human-subject trials presented in the prior art. KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), also discloses that if some teaching, suggestion, or motivation in the prior art would lead one skilled in the art before the effective filing date to combine prior art references, then the modification is obvious. The direct teaching by Navarro-Tapia et al regarding the motivation to administer probiotics during the first four weeks of life provides an obvious motivation for focusing on this timeframe.
Claims 2-5 and 11 depend on claim 1. The teachings of the references for claim 1 are described above and incorporated in its entirety for claims 2-5 and 11, and further described below.
Regarding claim 2, Vlieger et al further teaches continuing the method in newborn subjects at 3 months old to 6 months old.
Regarding claim 3, Biffi ‘179 claims 2 and 16 teaches the bacteria in the method are viable bacteria or derivatives of bacteria. Additionally, Vlieger et al (section Study formulas) and Cremon et al (section Study design) further teaches the method using viable strains of bacteria. Navarro-Tapia et al further teaches that derivatives of strains of bacteria, such as inactivated strains (also called paraprobiotics) could be useful for infants and vulnerable populations (page 38, paragraph 2).
Regarding claim 5, Biffi ‘179 claims 7-11 further teaches one food grade or pharmaceutical grade additive and/or excipient. Vlieger et al further teaches the method further comprises of a mixture of bacteria strains and at least one food grade or pharmaceutical grade additive and/or excipient, as they teach the strain was added to an infant formula mix that contains such additives, called Friso 1 (section Study formulas).
Regarding claim 4, Biffi ‘179 claim 1 and Cremon et al further teach the method wherein the disorder is IBS (Abstract).
Regarding claim 11, Vlieger et al further teaches the method wherein said disorders are selected from the group consisting of: neonatal colic, intestinal colic, chronic enterocolitis or chronic enterocolitis in preterm newborns and necrotizing enterocolitis, as evidenced by the increase in defecation frequency and softer stools (page 873, paragraph 2).
Claim 7 and 12 depend on claim 5, which depends on claim 1. The teachings of the references for claims 1 and 5 are described above and incorporated in its entirety for claims 7 and 12, and further described below.
Regarding claim 7, Vlieger et al further teaches the strain was added to an infant formula mix, called Friso 1 (section Study formulas), which contains, for example, GOS (galacto-oligosaccharide), zinc, and Vitamins B and D.
Regarding claim 12, Vlieger et al further teaches the limitations of claim 5 and Vlieger et al further teaches the method wherein said disorders are selected from the group consisting of: neonatal colic, intestinal colic, chronic enterocolitis or chronic enterocolitis in preterm newborns and necrotizing enterocolitis, as described for claim 1, as evidenced by the increase in defecation frequency and softer stools (page 873, paragraph 2).
Claim 9 depends on claim 3, which depends on claim 1. The teachings of the references for claims 1 and 3 are described above and incorporated in its entirety for claim 9, and further described below.
Regarding claim 9, Biffi ‘179 claim 2 teach the use of dead bacteria and Navarro-Tapia et al further teaches tyndallized probiotics for infants and vulnerable population (page 38, paragraph 2).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to combine components from each of the prior art references in light of the advantages taught. Regarding claims 3 and 9, it would be obvious to one skilled in the art, before the effective filing date of the instant application, that viable bacteria strains can be used in newborns, but the option to use derivatives of the bacteria strains may be considered for highly vulnerable populations. Regarding claims 4 and 11-12, it would be obvious to one skilled in the art, before the effective filing date of the instant application, that the bacteria strains taught by the prior art would be reasonable probiotic candidates for the gastro-intestinal disorders claimed, as the prior art teaches them for use in treating and/or preventing these gastrointestinal disorders. Regarding claims 5 and 7, it would be obvious that these bacterial strains could be formulated with the additives claimed, and would benefit from coformulation with additional components, such as prebiotics, in light of the art teaching the synergy of prebiotic oligosaccharides and beneficial bacteria (Navarro-Tapia et al, page 16).
One skilled in the art, before the effective filing date of the instant application, would be motivated to combine these beneficial elements in known disease models to reduce the risk of adverse effects and treat gastrointestinal disorders in newborns.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success with inactivated bacteria and the additional components in the formulation since these techniques and components are not specifically beneficial to the particular bacteria strains but rather for probiotics in general.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that combining prior art elements according to known methods to yield predictable results is obvious. The prior art includes each element claimed although not necessarily in a single reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference. The use of the particular strain from Cremon et al and Biffi ‘179 claim 1 likely does not preclude the addition of the additives, the use in the claimed disease models, the use of its derivatives, and the use in certain populations, as is relevant to these claims and taught by Vlieger et al and Navarro-Tapia et al. Therefore, one of ordinary skill in the art, before the effective filing date, could have combined the elements and each element would be expected to perform, at least, the same function as it does separately.
Claim 6 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. US11752179B2 (hereafter referred to as Biffi ‘179) in view of Vlieger et al and further in view of Cremon et al and further in view of Navarro-Tapia et al as applied to claims 1-5, 7, 9, 11-12 above, and further in view of Biffi WO‘458 (Biffi, A., WO2022208458A1, Inactivated strains of bacteria, such as viable but non-culturable bacteria, compositions and use thereof; Effectively filed 04/01/2021 by priority application IT102021000008300). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 6 depends on claim 5, which depends on claim 1. The teachings of the references for claims 5 and 1 are discussed above and incorporated in its entirety for claim 6 and further discussed below.
Biffi ‘179 claim 13 further teaches the method comprising of other microorganisms. Vlieger et al teaches the method comprising of a mixture of Lactobacillus paracasei and Bifidobacterium animalis ssp. Lactis in an infant formula (Abstract).
Biffi ‘179 claim 13 in view of Vlieger et al and further in view of Cremon et al and further in view of Navarro-Tapia et al do not explicitly teach the instantly claimed strain of Bifidobacterium animalis ssp. Lactis.
However, Biffi WO‘458 teaches the instantly claimed strain Bifidobacterium breve DSM 33231, Bifidobacterium breve DSM 33232, Bifidobacterium animalis subsp. Lactis DSM 33233, Lactobacillus plantarum DSM 33234, and Bifidobacterium bifidum BbfIBS0l DSM 32708 in methods for the preventive and/or curative treatment of gastrointestinal diseases, disorders or symptoms (page 1, paragraphs 1-3).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that combining two bacteria species of the Lactobacillus and/or Bifidobacterium, is possible and beneficial, in light of Vlieger et at teaching this combination and the art especially recognizing the benefits of mixtures of Lactobacillus and Bifidobacterium species (Navarro-Tapia et al, Abstract). It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to choose from the list of strains provided by Biffi WO’458 as these strains were already disclosed to treat gastrointestinal diseases.
One skilled in the art, before the effective filing date of the instant application, would be motivated to use the combination of two bacteria species known in the art and choose specific strains for the particular desired purpose based on teachings of the prior art about these strains, as both bacteria have different beneficial but compatible effects. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success in the method to treat gastrointestinal diseases as these strains were already disclosed to treat gastrointestinal diseases.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that use of a known technique to improve similar methods or products in the same way is obvious. The combination of bacteria species to improve on formulations with single bacteria species are known techniques used to improve probiotic formulations that can be applied to the relevant probiotic strains taught in the art, to arrive at the claimed invention. Although the prior art teaches the specific bacteria strains in different references, the bacteria strains and its uses are comparable and therefore, could benefit from the same improvement when combined with other probiotic bacteria, and the results would still be reasonably predictable.
Claim 6 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. US11752179B2 (hereafter referred to as Biffi ‘179) in view of Vlieger et al and further in view of Cremon et al and further in view of Navarro-Tapia et al as applied to claims 1-5, 7, 9, 11-12 above, and further in view of Biffi WO’636 (Biffi, A., et al, WO2021053636A1, Bacterial strains, their compositions and their use for the treatment of gastrointestinal disorders; published 03/25/2021). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 6 depends on claim 5, which depends on claim 1. The teachings of the references for claims 5 and 1 are discussed above and incorporated in its entirety for claim 6 and further discussed below.
Biffi ‘179 claim 13 teaches the method comprises of other microorganisms. Vlieger et al teaches the method comprising of a mixture of Lactobacillus paracasei and Bifidobacterium animalis ssp. Lactis in an infant formula (Abstract).
Biffi ‘179 in view of Vlieger et al and further in view of Cremon et al and further in view of Navarro-Tapia et al do not explicitly teach the instantly claimed strain of Bifidobacterium animalis ssp. Lactis.
However, Biffi WO‘636 teaches the instantly claimed strain Bifidobacterium breve DSM 33231, Bifidobacterium breve DSM 33232, Bifidobacterium animalis subsp. Lactis DSM 33233, Lactobacillus plantarum DSM 33234, and Bifidobacterium bifidum BbfIBS0l DSM 32708 in methods for the preventive and/or curative treatment of gastrointestinal diseases, disorders or symptoms (page 1, paragraphs 1-3).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that combining two bacteria species of the Lactobacillus and/or Bifidobacterium, is possible and beneficial, in light of Vlieger et at teaching this combination and the art especially recognizing the benefits of mixtures of Lactobacillus and Bifidobacterium species (Navarro-Tapia et al, Abstract). It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to choose from the list of strains provided by Biffi WO’636 as these strains were already disclosed to treat gastrointestinal diseases.
One skilled in the art, before the effective filing date of the instant application, would be motivated to use the combination of two bacteria species known in the art and choose specific strains for the particular desired purpose based on teachings of the prior art about these strains, as both bacteria have different beneficial but compatible effects. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success in the method to treat gastrointestinal diseases as these strains were already disclosed to treat gastrointestinal diseases.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that use of a known technique to improve similar methods or products in the same way is obvious. The combination of bacteria species to improve on formulations with single bacteria species are known techniques used to improve probiotic formulations that can be applied to the relevant probiotic strains taught in the art, to arrive at the claimed invention. Although the prior art teaches the specific bacteria strains in different references, the bacteria strains and its uses are comparable and therefore, could benefit from the same improvement when combined with other probiotic bacteria, and the results would still be reasonably predictable.
Claim 8 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. US11752179B2 (hereafter referred to as Biffi ‘179) in view of Vlieger et al and further in view of Cremon et al and further in view of Navarro-Tapia et al as applied to claims 1-5, 7, 9, 11-12 above, and further in view of Malfa et al (Malfa, P., et al, IT201900000801A1, Composition including non-viable probiotic bacteria and its use in therapy; published 07/18/2020). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 8 depends on claim 3, which depends on claim 1. The teachings of the references for claims 3 and 1 are discussed above and incorporated in its entirety for claim 6 and further discussed below.
Biffi ‘179 claim 2 teaches the use of dead bacteria in the method and Navarro-Tapia et al further teaches that derivatives of strains of bacteria, such as inactivated strains (also called paraprobiotics) could be useful for infants and vulnerable populations.
Biffi ‘179 in view of Vlieger et al and further in view of Cremon et al and further in view of Navarro-Tapia et al do not explicitly teach the bacterial strain is gamma irradiated.
However, Malfa et al teaches the bacterial strain is gamma irradiated.
Malfa et al teaches the disadvantages of other methods of bacteria inactivation (section State of the Art) and contrast it to inactivation by gamma rays, which maintain integrity of the bacteria cell wall, which allow it to maintain adhesive properties, which is helpful for remaining at the target site (Description of the invention). Malfa et al teaches this method can be applied to Lactobacillus paracasei (Description of the invention).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that gamma irradiated bacteria strains could be advantageous for probiotic functions over other methods of bacteria inactivation, according to the teachings of Malfa et al, and that although Malfa et al teaches their method with topical administration of the bacteria, the benefits are applicable to the gastrointestinal environment.
One skilled in the art, before the effective filing date of the instant application, would be motivated to utilize gamma irradiation to inactivate probiotic bacteria in light of the potential drawbacks taught for other common methods of bacteria inactivation.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success because this combination of bacteria species is already taught in the art to provide a multi-pronged approach to treatment. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success with gamma irradiated bacteria as it has been taught to be a suitable and perhaps better substitute for heat-inactivated probiotic bacteria or other common methods of inactivation, as it helps retain the ability for the bacteria to adhere to the intestinal wall, where it needs to work, but reduces potential undesired reactions against a live probiotic that may be especially salient in newborn subjects.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that use of a known technique to improve similar methods or products in the same way is obvious. The use of gamma irradiation to improve on probiotics inactivated by other methods are known techniques used to improve probiotic formulations that can be applied to the relevant probiotic strains taught in the art, to arrive at the claimed invention.
Claim 10 is rejected on the ground of nonstatutory double patenting as being unpatentable claims 1-16 of U.S. Patent No. US11752179B2 (hereafter referred to as Biffi ‘179) in view of Vlieger et al and further in view of Cremon et al and further in view of Navarro-Tapia et al as applied to claims 1-5, 7, 9, 11-12 above, and further in view of Dilli et al (Dilli, D., et al, The ProPre-Save Study: Effects of Probiotics and Prebiotics Alone or Combined on Necrotizing Enterocolitis in Very Low Birth Weight Infants, J Pediatr 2015;166:545-51; published 03/2015). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 10 depends on claim 7, which depends on claim 5, which depends on claim 1. The teachings of the references for claims 5 and 7 are discussed above and incorporated in its entirety for claim 10 and further discussed below.
Vlieger et al further teaches the strain was added to an infant formula mix, called Friso 1 (section Study formula), which contains Vitamins B and D. Vlieger et al further teaches a prebiotic-containing formula was chosen (section Study formula).
Biffi ‘179 in view of Vlieger et al and further in view of Cremon et al and further in view of Navarro-Tapia et al does not explicitly teach at least one prebiotic is inulin.
However, Dilli et al teaches a synbiotic comprising of inulin and Bifidobacterium lactis (also known as Bifidobacterium animalis subsp. Lactis) for infants to prevent necrotizing enterocolitis (NEC). Dilli et al further teaches inulin as a prebiotic sugar that stimulate the growth and metabolic activity of beneficial bacteria. Dilli et al provides a list of exemplary prebiotic sugars including inulin and galacto-oligosaccharide (Abstract) and therefore they can be understood by one skilled in the art, before the effective filing date, that these prebiotic sugars may be suitable alternatives to choose from depending on its utility to specific bacteria probiotic. Dilli et al further teaches that both normal flora Bifidobacterium and Lactobacillus spp. colonization is delayed in premature infants (Discussion paragraph 1). As such, one would be motivated to also use inulin with Lactobacillus species, arriving at the claimed invention.
In summary, Vlieger et al teaches probiotics Lactobacillus paracasei and Bifidobacterium animalis subsp. Lactis with prebiotic galacto-oligosaccharide while Dilli et al teaches Bifidobacterium animalis subsp. Lactis with prebiotic inulin but teaches inulin and galacto-oligosaccharide as prebiotics (Abstract). It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that the galacto-oligosaccharide could be substituted with inulin as the prebiotic for formulations comprising of Lactobacillus paracasei as both sugars are used to stimulate probiotic growth.
One skilled in the art, before the effective filing date of the instant application, would be motivated to try the inulin as a prebiotic for Lactobacillus paracasei, as Dilli et al teaches that Lactobacillus and Bifidobacterium are two normal bacterial flora (Discussion, paragraph 1), and therefore, are often probiotic candidates administered together, as taught by Vlieger et al. As such, since inulin is shown to work for Bifidobacterium, it would be useful to try this with Lactobacillus to see if inulin can be used for both probiotics, which could be especially useful in probiotic combinations.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success since these common prebiotics are chosen for their ability to be metabolized by many bacterial species.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success is obvious. Dilli et al teaches a finite number of identified predictable potential solutions (i.e. prebiotics) that could be useful with the probiotic bacteria. One skilled in the art, before the effective filing date of the instant application, could have pursued the known potential prebiotics with reasonable expectation of success with the two common species of probiotics.
Although Biffi ‘179 claims 3-6, 12, and14-15 are not explicitly referred to in this rejection, they provide additional details that may be relevant to the instantly claimed invention and thus are acknowledged here for the record.
U.S. Patent No. US12447183B2
Claims 1-5, 7, 9, 11-12 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. US12447183B2 (hereafter referred to as Biffi ‘183) in view of Vlieger et al (Vlieger, A., et al, Tolerance and safety of Lactobacillus paracasei ssp. paracasei in combination with Bifidobacterium animalis ssp. lactis in a prebiotic-containing infant formula: a randomised controlled trial, British Journal of Nutrition, 102, 869–875; published 03/31/2009) and further in view of Cremon et al (Cremon, C., et al, Effect of Lactobacillus paracasei CNCM I-1572 on symptoms, gut microbiota, short chain fatty acids, and immune activation in patients with irritable bowel syndrome: A pilot randomized clinical trial ; published 05/2018) and further in view of Navarro-Tapia et al (Navarro-Tapia, E., et al, Probiotic Supplementation during the Perinatal and Infant Period: Effects on gut Dysbiosis and Disease, Nutrients 2020, 12, 2243, published 07/27/2020). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant specification defines a “method of treating” to include “the elimination, reduction/decrease or prevention of a pathology or disease and related symptoms or disorders” (page 10, line 6-9).
Regarding instant claim 1, Biffi ‘183 claims 1-2 and 4-5 teaches a method of treating subjects suffering from IBS with Lactobacillus paracasei DG I-1572 and/or Lactobacillus paracasei LPC-SOl DSM 26760, which are the two strains of the instant claim. Cremon et al also teaches Lactobacillus paracasei DG CNCM I-1572. Cremon et al teaches Lactobacillus paracasei DG® CNCM I-1572 has effects on the reduction/decrease or prevention of a pathology or disease and related symptoms or disorders in subjects with IBS. Cremon et al teaches that subjects treated with Lactobacillus paracasei DG® CNCM I-1572 showed reduced presence of a bacteria genus associated with IBS (page 609), and reduced pro-inflammatory cytokine IL-15 levels which is taught to play a primary role in the development of several inflammatory diseases, such as IBS (page 611).
Biffi ‘183 does not explicitly teach the subject is a newborn subject in the first four weeks of life.
However, Vlieger et al teaches a method of treating and/or preventing gastrointestinal related disorders of an inflammatory and/or functional nature in a subject in need thereof with a composition comprising of bacteria strains (Abstract). Vlieger et al teach that the strain of bacteria is a Lactobacillus paracasei strain (Abstract). Vlieger et al teaches that the effect of this treatment was softer stool and increased defecation frequency in the subject, which is a reduction of a related symptom of the claimed disorders, such as intestinal colic, IBS with alternating bowel (also known as IBS-M/Mixed) and IBS with prevalent constipation or constipated bowel (also known as IBS-C/with Constipation) (section Discussion).
Vlieger et al does teach the method in newborns starting from at most 7 days of age until 3 months of age (section Subjects and section Trial Design).
Biffi ‘183 claims 1-2 and 4-5 in view of Vlieger et al and further in view of Cremon et al do not explicitly teach the subject is a newborn subject in the first four weeks of life.
However, Navarro-Tapia et al teaches the importance of the perinatal period, which starts at the 20th week of gestation and ends 4 weeks after birth, in establishing lifelong gut microbiota; and that use of probiotics and paraprobiotics as therapeutic tools is attracting great interest, especially in the perinatal period (Abstract), providing motivation for focusing on the specific timeframe in claim 1, arriving at all the limitations of claim 1.
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to substitute the Lactobacillus paracasei strain taught by Vlieger et al with the Lactobacillus paracasei strain taught by Biffi ‘183 claims 1-2 and 4-5 and Cremon et al in light of the finding that this strain can reduce bacteria and cytokines associated with IBS and gastrointestinal inflammatory diseases. It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to specifically focus on administration during the four weeks after birth during the perinatal phase, taught by Navarro-Tapia et al as critical to the lifelong health of the infant.
Vlieger et al teaches a study that comprised of healthy newborn subjects. In contrast, Biffi ‘183 claims 1-2 and 4-5 and Cremon et al teaches subjects suffering from IBS. One skilled in the art, before the effective filing date of the instant application, would be motivated to harness the advantages of the Lactobacillus paracasei strain taught by Biffi ‘183 claims 1-2 and 4-5 and Cremon et al for newborns with IBS or other related pathologies. One skilled in the art, before the effective filing date of the instant application, would be motivated to administer these beneficial probiotics during a defined period that is critical to the lifelong health of the infant.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success due to the findings of no treatment-related adverse effects for the Lactobacillus paracasei strain and its treatment potential in IBS taught by Biffi ‘183 claims 1-2 and 4-5 and Cremon et al. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success due to the examples supporting probiotic supplementation during the perinatal period taught by Navarro-Tapia et al (reviewed throughout Table 6).
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that a simple substitution of one known element for another to obtain predictable results is obvious. The prior art contained a method that differed from the instant application by the substitution of the Lactobacillus paracasei strain with another Lactobacillus paracasei strain taught in the copending application and Cremon et al. Therefore, the substituted components and their functions were known in the art to serve similar purposes in treating and/or preventing gastro-intestinal disorders of an inflammatory and/or functional nature. One of ordinary skill in the art, before the effective filing date, could have substituted on known element for another, and the results of the substitution would have bene predictable in light of the human-subject trials presented in the prior art. KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), also discloses that if some teaching, suggestion, or motivation in the prior art would lead one skilled in the art before the effective filing date to combine prior art references, then the modification is obvious. The direct teaching by Navarro-Tapia et al regarding the motivation to administer probiotics during the first four weeks of life provides an obvious motivation for focusing on this timeframe.
Claims 2-5 and 11 depend on claim 1. The teachings of the references for claim 1 are described above and incorporated in its entirety for claims 2-5 and 11, and further described below.
Regarding claim 2, Vlieger et al further teaches continuing the method in newborn subjects at 3 months old to 6 months old.
Regarding claim 3, Vlieger et al (section Study formulas) and Cremon et al (section Study design) further teaches the method using viable strains of bacteria. Navarro-Tapia et al further teaches that derivatives of strains of bacteria, such as inactivated strains (also called paraprobiotics) could be useful for infants and vulnerable populations (page 38, paragraph 2).
Regarding claim 5, Vlieger et al further teaches the method further comprises of a mixture of bacteria strains and at least one food grade or pharmaceutical grade additive and/or excipient, as they teach the strain was added to an infant formula mix that contains such additives, called Friso 1 (section Study formulas).
Regarding claim 4, Biffi ‘183 claims 1-2 and 4-5, and Cremon et al further teach the method wherein the disorder is IBS (Abstract).
Regarding claim 11, Vlieger et al further teaches the method wherein said disorders are selected from the group consisting of: neonatal colic, intestinal colic, chronic enterocolitis or chronic enterocolitis in preterm newborns and necrotizing enterocolitis, as evidenced by the increase in defecation frequency and softer stools (page 873, paragraph 2).
Claim 7 and 12 depend on claim 5, which depends on claim 1. The teachings of the references for claims 1 and 5 are described above and incorporated in its entirety for claims 7 and 12, and further described below.
Regarding claim 7, Vlieger et al further teaches the strain was added to an infant formula mix, called Friso 1, which contains, for example, GOS (galacto-oligosaccharide), zinc, and Vitamins B and D (section Study formulas).
Regarding claim 12, Vlieger et al further teaches the limitations of claim 5 and Vlieger et al further teaches the method wherein said disorders are selected from the group consisting of: neonatal colic, intestinal colic, chronic enterocolitis or chronic enterocolitis in preterm newborns and necrotizing enterocolitis, as described for claim 1, as evidenced by the increase in defecation frequency and softer stools (page 873, paragraph 2).
Claim 9 depends on claim 3, which depends on claim 1. The teachings of the references for claims 1 and 3 are described above and incorporated in its entirety for claim 9, and further described below.
Regarding claim 9, Navarro-Tapia et al further teaches tyndallized probiotics for infants and vulnerable population (page 38, paragraph 2).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to combine components from each of the prior art references in light of the advantages taught. Regarding claims 3 and 9, it would be obvious to one skilled in the art, before the effective filing date of the instant application, that viable bacteria strains can be used in newborns, but the option to use derivatives of the bacteria strains may be considered for highly vulnerable populations. Regarding claims 4 and 11-12, it would be obvious to one skilled in the art, before the effective filing date of the instant application, that the bacteria strains taught by the prior art would be reasonable probiotic candidates for the gastro-intestinal disorders claimed, as the prior art teaches them for use in treating and/or preventing these gastrointestinal disorders. Regarding claims 5 and 7, it would be obvious that these bacterial strains could be formulated with the additives claimed, and would benefit from coformulation with additional components, such as prebiotics, in light of the art teaching the synergy of prebiotic oligosaccharides and beneficial bacteria (Navarro-Tapia et al, page 16).
One skilled in the art, before the effective filing date of the instant application, would be motivated to combine these beneficial elements in known disease models to reduce the risk of adverse effects and treat gastrointestinal disorders in newborns.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success with inactivated bacteria and the additional components in the formulation since these techniques and components are not specifically beneficial to the particular bacteria strains but rather for probiotics in general.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that combining prior art elements according to known methods to yield predictable results is obvious. The prior art includes each element claimed although not necessarily in a single reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference. The use of the particular strain from Cremon et al and Biffi ‘784 claim 1 likely does not preclude the addition of the additives, the use in the claimed disease models, the use of its derivatives, and the use in certain populations, as is relevant to these claims and taught by Vlieger et al and Navarro-Tapia et al. Therefore, one of ordinary skill in the art, before the effective filing date, could have combined the elements and each element would be expected to perform, at least, the same function as it does separately.
Claim 6 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. US12447183B2 (hereafter referred to as Biffi ‘183) in view of Vlieger et al and further in view of Cremon et al and further in view of Navarro-Tapia et al as applied to claims 1-5, 7, 9, 11-12 above, and further in view of Biffi WO‘458 (Biffi, A., WO2022208458A1, Inactivated strains of bacteria, such as viable but non-culturable bacteria, compositions and use thereof; Effectively filed 04/01/2021 by priority application IT102021000008300). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 6 depends on claim 5, which depends on claim 1. The teachings of the references for claims 5 and 1 are discussed above and incorporated in its entirety for claim 6 and further discussed below.
Vlieger et al teaches the method comprising of a mixture of Lactobacillus paracasei and Bifidobacterium animalis ssp. Lactis in an infant formula (Abstract).
Vlieger et al in view of Cremon et al and further in view of Navarro-Tapia et al do not explicitly teach the instantly claimed strain of Bifidobacterium animalis ssp. Lactis.
However, Biffi WO‘458 teaches the instantly claimed strain Bifidobacterium breve DSM 33231, Bifidobacterium breve DSM 33232, Bifidobacterium animalis subsp. Lactis DSM 33233, Lactobacillus plantarum DSM 33234, and Bifidobacterium bifidum BbfIBS0l DSM 32708 in methods for the preventive and/or curative treatment of gastrointestinal diseases, disorders or symptoms (page 1, paragraphs 1-3). Furthermore, Biffi ‘183 claims 1-5 also teaches all the strains instantly claimed, and in combination with the Lactobacillus paracasei DG® CNCM 1-1572 and/or Lactobacillus paracasei LPC-SOl DSM 26760, arriving at the limitations of the instant claim.
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that combining two bacteria species of the Lactobacillus and/or Bifidobacterium, is possible and beneficial, in light of Vlieger et at teaching this combination and the art especially recognizing the benefits of mixtures of Lactobacillus and Bifidobacterium species (Navarro-Tapia et al, Abstract). It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to choose from the list of strains provided by Biffi WO’458 as these strains were already disclosed to treat gastrointestinal diseases and further taught by Biffi ‘183 in methods to treat IBS alone and in combination with the Lactobacillus paracasei DG® CNCM 1-1572 and/or Lactobacillus paracasei LPC-SOl DSM 26760.
One skilled in the art, before the effective filing date of the instant application, would be motivated to use the combination of two bacteria species known in the art and choose specific strains for the particular desired purpose based on teachings of the prior art about these strains, as both bacteria have different beneficial but compatible effects. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success in the method to treat gastrointestinal diseases as these strains were already disclosed to treat gastrointestinal diseases.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that use of a known technique to improve similar methods or products in the same way is obvious. The combination of bacteria species to improve on formulations with single bacteria species are known techniques used to improve probiotic formulations that can be applied to the relevant probiotic strains taught in the art, to arrive at the claimed invention. Although the prior art teaches the specific bacteria strains in different references, the bacteria strains and its uses are comparable and therefore, could benefit from the same improvement when combined with other probiotic bacteria, and the results would still be reasonably predictable.
Claim 6 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. US12447183B2 (hereafter referred to as Biffi ‘183) in view of Vlieger et al and further in view of Cremon et al and further in view of Navarro-Tapia et al as applied to claims 1-5, 7, 9, 11-12 above, and further in view of Biffi WO’636 (Biffi, A., et al, WO2021053636A1, Bacterial strains, their compositions and their use for the treatment of gastrointestinal disorders; published 03/25/2021). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 6 depends on claim 5, which depends on claim 1. The teachings of the references for claims 5 and 1 are discussed above and incorporated in its entirety for claim 6 and further discussed below.
Vlieger et al teaches the method comprising of a mixture of Lactobacillus paracasei and Bifidobacterium animalis ssp. Lactis in an infant formula (Abstract).
Vlieger et al in view of Cremon et al and further in view of Navarro-Tapia et al do not explicitly teach the instantly claimed strain of Bifidobacterium animalis ssp. Lactis.
However, Biffi WO‘636 teaches the instantly claimed strain Bifidobacterium breve DSM 33231, Bifidobacterium breve DSM 33232, Bifidobacterium animalis subsp. Lactis DSM 33233, Lactobacillus plantarum DSM 33234, and Bifidobacterium bifidum BbfIBS0l DSM 32708 in methods for the preventive and/or curative treatment of gastrointestinal diseases, disorders or symptoms (page 1, paragraphs 1-3). Furthermore, Biffi ‘183 claims 1-5 also teaches all the strains instantly claimed, and in combination with the Lactobacillus paracasei DG® CNCM 1-1572 and/or Lactobacillus paracasei LPC-SOl DSM 26760, arriving at the limitations of the instant claim.
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that combining two bacteria species of the Lactobacillus and/or Bifidobacterium, is possible and beneficial, in light of Vlieger et at teaching this combination and the art especially recognizing the benefits of mixtures of Lactobacillus and Bifidobacterium species (Navarro-Tapia et al, Abstract). It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to choose from the list of strains provided by Biffi WO’636 as these strains were already disclosed to treat gastrointestinal diseases and further taught by Biffi ‘183 in methods to treat IBS alone and in combination with the Lactobacillus paracasei DG® CNCM 1-1572 and/or Lactobacillus paracasei LPC-SOl DSM 26760.
One skilled in the art, before the effective filing date of the instant application, would be motivated to use the combination of two bacteria species known in the art and choose specific strains for the particular desired purpose based on teachings of the prior art about these strains, as both bacteria have different beneficial but compatible effects. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success in the method to treat gastrointestinal diseases as these strains were already disclosed to treat gastrointestinal diseases.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that use of a known technique to improve similar methods or products in the same way is obvious. The combination of bacteria species to improve on formulations with single bacteria species are known techniques used to improve probiotic formulations that can be applied to the relevant probiotic strains taught in the art, to arrive at the claimed invention. Although the prior art teaches the specific bacteria strains in different references, the bacteria strains and its uses are comparable and therefore, could benefit from the same improvement when combined with other probiotic bacteria, and the results would still be reasonably predictable.
Claim 8 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. US12447183B2 (hereafter referred to as Biffi ‘183) in view of Vlieger et al and further in view of Cremon et al and further in view of Navarro-Tapia et al as applied to claims 1-5, 7, 9, 11-12 above, and further in view of Malfa et al (Malfa, P., et al, IT201900000801A1, Composition including non-viable probiotic bacteria and its use in therapy; published 07/18/2020). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 8 depends on claim 3, which depends on claim 1. The teachings of the references for claims 3 and 1 are discussed above and incorporated in its entirety for claim 6 and further discussed below.
Navarro-Tapia et al further teaches that derivatives of strains of bacteria, such as inactivated strains (also called paraprobiotics) could be useful for infants and vulnerable populations.
Biffi ‘183 in view of Vlieger et al and further in view of Cremon et al and further in view of Navarro-Tapia et al do not explicitly teach the bacterial strain is gamma irradiated.
However, Malfa et al teaches the bacterial strain is gamma irradiated.
Malfa et al teaches the disadvantages of other methods of bacteria inactivation (section State of the Art) and contrast it to inactivation by gamma rays, which maintain integrity of the bacteria cell wall, which allow it to maintain adhesive properties, which is helpful for remaining at the target site (Description of the invention). Malfa et al teaches this method can be applied to Lactobacillus paracasei (Description of the invention).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that gamma irradiated bacteria strains could be advantageous for probiotic functions over other methods of bacteria inactivation, according to the teachings of Malfa et al, and that although Malfa et al teaches their method with topical administration of the bacteria, the benefits are applicable to the gastrointestinal environment.
One skilled in the art, before the effective filing date of the instant application, would be motivated to utilize gamma irradiation to inactivate probiotic bacteria in light of the potential drawbacks taught for other common methods of bacteria inactivation.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success because this combination of bacteria species is already taught in the art to provide a multi-pronged approach to treatment. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success with gamma irradiated bacteria as it has been taught to be a suitable and perhaps better substitute for heat-inactivated probiotic bacteria or other common methods of inactivation, as it helps retain the ability for the bacteria to adhere to the intestinal wall, where it needs to work, but reduces potential undesired reactions against a live probiotic that may be especially salient in newborn subjects.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that use of a known technique to improve similar methods or products in the same way is obvious. The use of gamma irradiation to improve on probiotics inactivated by other methods are known techniques used to improve probiotic formulations that can be applied to the relevant probiotic strains taught in the art, to arrive at the claimed invention.
Claim 10 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. US12447183B2 (hereafter referred to as Biffi ‘183) in view of Vlieger et al and further in view of Cremon et al and further in view of Navarro-Tapia et al as applied to claims 1-5, 7, 9, 11-12 above, and further in view of Dilli et al (Dilli, D., et al, The ProPre-Save Study: Effects of Probiotics and Prebiotics Alone or Combined on Necrotizing Enterocolitis in Very Low Birth Weight Infants, J Pediatr 2015;166:545-51; published 03/2015). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 10 depends on claim 7, which depends on claim 5, which depends on claim 1. The teachings of the references for claims 5 and 7 are discussed above and incorporated in its entirety for claim 10 and further discussed below.
Vlieger et al further teaches the strain was added to an infant formula mix, called Friso 1 (section Study formula), which contains Vitamins B and D. Vlieger et al further teaches a prebiotic-containing formula was chosen (section Study formula).
Biffi ‘183 in view of Vlieger et al and further in view of Cremon et al and further in view of Navarro-Tapia et al does not explicitly teach at least one prebiotic is inulin.
However, Dilli et al teaches a synbiotic comprising of inulin and Bifidobacterium lactis (also known as Bifidobacterium animalis subsp. Lactis) for infants to prevent necrotizing enterocolitis (NEC). Dilli et al further teaches inulin as a prebiotic sugar that stimulate the growth and metabolic activity of beneficial bacteria. Dilli et al provides a list of exemplary prebiotic sugars including inulin and galacto-oligosaccharide (Abstract) and therefore they can be understood by one skilled in the art, before the effective filing date, that these prebiotic sugars may be suitable alternatives to choose from depending on its utility to specific bacteria probiotic. Dilli et al further teaches that both normal flora Bifidobacterium and Lactobacillus spp. colonization is delayed in premature infants (Discussion paragraph 1). As such, one would be motivated to also use inulin with Lactobacillus species, arriving at the claimed invention.
In summary, Vlieger et al teaches probiotics Lactobacillus paracasei and Bifidobacterium animalis subsp. Lactis with prebiotic galacto-oligosaccharide; Biffi ‘183 teaches the specific instantly claimed strains, alone or in combination; while Dilli et al teaches Bifidobacterium animalis subsp. Lactis with prebiotic inulin but teaches inulin and galacto-oligosaccharide as prebiotics (Abstract). It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that the galacto-oligosaccharide could be substituted with inulin as the prebiotic for formulations comprising of Lactobacillus paracasei as both sugars are used to stimulate probiotic growth.
One skilled in the art, before the effective filing date of the instant application, would be motivated to try the inulin as a prebiotic for Lactobacillus paracasei, as Dilli et al teaches that Lactobacillus and Bifidobacterium are two normal bacterial flora (Discussion, paragraph 1), and therefore, are often probiotic candidates administered together, as taught by Vlieger et al. As such, since inulin is shown to work for Bifidobacterium, it would be useful to try this with Lactobacillus to see if inulin can be used for both probiotics, which could be especially useful in probiotic combinations.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success since these common prebiotics are chosen for their ability to be metabolized by many bacterial species.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success is obvious. Dilli et al teaches a finite number of identified predictable potential solutions (i.e. prebiotics) that could be useful with the probiotic bacteria. One skilled in the art, before the effective filing date of the instant application, could have pursued the known potential prebiotics with reasonable expectation of success with the two common species of probiotics.
Application No. 18865784
Claims 1-5, 7, 9, 11-12 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-3 and 5-16 of copending Application No. 18865784 (hereafter referred to as Biffi ‘784) in view of Vlieger et al (Vlieger, A., et al, Tolerance and safety of Lactobacillus paracasei ssp. paracasei in combination with Bifidobacterium animalis ssp. lactis in a prebiotic-containing infant formula: a randomised controlled trial, British Journal of Nutrition, 102, 869–875; published 03/31/2009) in view of Cremon et al (Cremon, C., et al, Effect of Lactobacillus paracasei CNCM I-1572 on symptoms, gut microbiota, short chain fatty acids, and immune activation in patients with irritable bowel syndrome: A pilot randomized clinical trial ; published 05/2018) and further in view of Navarro-Tapia et al (Navarro-Tapia, E., et al, Probiotic Supplementation during the Perinatal and Infant Period: Effects on gut Dysbiosis and Disease, Nutrients 2020, 12, 2243, published 07/27/2020). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant specification defines a “method of treating” to include “the elimination, reduction/decrease or prevention of a pathology or disease and related symptoms or disorders” (page 10, line 6-9).
Regarding instant claim 1, Biffi ‘784 claim 1 teaches a method of treating subjects suffering from IBS with Lacticaseibacillus paracasei DG I-1572, which is another name for Lactobacillus paracasei DG CNCM I-1572 of the instant claim. Cremon et al also teaches Lactobacillus paracasei DG CNCM I-1572. Cremon et al teaches Lactobacillus paracasei DG® CNCM I-1572 has effects on the reduction/decrease or prevention of a pathology or disease and related symptoms or disorders in subjects with IBS. Cremon et al teaches that subjects treated with Lactobacillus paracasei DG® CNCM I-1572 showed reduced presence of a bacteria genus associated with IBS (page 609), and reduced pro-inflammatory cytokine IL-15 levels which is taught to play a primary role in the development of several inflammatory diseases, such as IBS (page 611).
Biffi ‘784 does not explicitly teach the subject is a newborn subject in the first four weeks of life.
However, Vlieger et al teaches a method of treating and/or preventing gastrointestinal related disorders of an inflammatory and/or functional nature in a subject in need thereof with a composition comprising of bacteria strains (Abstract). Vlieger et al teach that the strain of bacteria is a Lactobacillus paracasei strain (Abstract). Vlieger et al teaches that the effect of this treatment was softer stool and increased defecation frequency in the subject, which is a reduction of a related symptom of the claimed disorders, such as intestinal colic, IBS with alternating bowel (also known as IBS-M/Mixed) and IBS with prevalent constipation or constipated bowel (also known as IBS-C/with Constipation) (section Discussion).
Vlieger et al does teach the method in newborns starting from at most 7 days of age until 3 months of age (section Subjects and section Trial Design).
Biffi ‘784 claim 1 in view of Vlieger et al and further in view of Cremon et al do not explicitly teach the subject is a newborn subject in the first four weeks of life.
However, Navarro-Tapia et al teaches the importance of the perinatal period, which starts at the 20th week of gestation and ends 4 weeks after birth, in establishing lifelong gut microbiota; and that use of probiotics and paraprobiotics as therapeutic tools is attracting great interest, especially in the perinatal period (Abstract), providing motivation for focusing on the specific timeframe in claim 1, arriving at all the limitations of claim 1.
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to substitute the Lactobacillus paracasei strain taught by Vlieger et al with the Lactobacillus paracasei strain taught by Biffi ‘784 claim 1 and Cremon et al in light of the finding that this strain can reduce bacteria and cytokines associated with IBS and gastrointestinal inflammatory diseases. It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to specifically focus on administration during the four weeks after birth during the perinatal phase, taught by Navarro-Tapia et al as critical to the lifelong health of the infant.
Vlieger et al teaches a study that comprised of healthy newborn subjects. In contrast, Biffi ‘784 claim 1 and Cremon et al teaches subjects suffering from IBS. One skilled in the art, before the effective filing date of the instant application, would be motivated to harness the advantages of the Lactobacillus paracasei strain taught by Biffi ‘784 claim 1 and Cremon et al for newborns with IBS or other related pathologies. One skilled in the art, before the effective filing date of the instant application, would be motivated to administer these beneficial probiotics during a defined period that is critical to the lifelong health of the infant.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success due to the findings of no treatment-related adverse effects for the Lactobacillus paracasei strain and its treatment potential in IBS taught by Biffi ‘784 claim 1 and Cremon et al. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success due to the examples supporting probiotic supplementation during the perinatal period taught by Navarro-Tapia et al (reviewed throughout Table 6).
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that a simple substitution of one known element for another to obtain predictable results is obvious. The prior art contained a method that differed from the instant application by the substitution of the Lactobacillus paracasei strain with another Lactobacillus paracasei strain taught in the copending application and Cremon et al. Therefore, the substituted components and their functions were known in the art to serve similar purposes in treating and/or preventing gastro-intestinal disorders of an inflammatory and/or functional nature. One of ordinary skill in the art, before the effective filing date, could have substituted on known element for another, and the results of the substitution would have bene predictable in light of the human-subject trials presented in the prior art. KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), also discloses that if some teaching, suggestion, or motivation in the prior art would lead one skilled in the art before the effective filing date to combine prior art references, then the modification is obvious. The direct teaching by Navarro-Tapia et al regarding the motivation to administer probiotics during the first four weeks of life provides an obvious motivation for focusing on this timeframe.
Claims 2-5 and 11 depend on claim 1. The teachings of the references for claim 1 are described above and incorporated in its entirety for claims 2-5 and 11, and further described below.
Regarding claim 2, Vlieger et al further teaches continuing the method in newborn subjects at 3 months old to 6 months old.
Regarding claim 3, Vlieger et al (section Study formulas) and Cremon et al (section Study design) further teaches the method using viable strains of bacteria. Navarro-Tapia et al further teaches that derivatives of strains of bacteria, such as inactivated strains (also called paraprobiotics) could be useful for infants and vulnerable populations (page 38, paragraph 2).
Regarding claim 5, Vlieger et al further teaches the method further comprises of a mixture of bacteria strains and at least one food grade or pharmaceutical grade additive and/or excipient, as they teach the strain was added to an infant formula mix that contains such additives, called Friso 1 (section Study formulas).
Regarding claim 4, Biffi ‘784 claims 1 and 6, and Cremon et al further teach the method wherein the disorder is IBS (Abstract).
Regarding claim 11, Vlieger et al further teaches the method wherein said disorders are selected from the group consisting of: neonatal colic, intestinal colic, chronic enterocolitis or chronic enterocolitis in preterm newborns and necrotizing enterocolitis, as evidenced by the increase in defecation frequency and softer stools (page 873, paragraph 2).
Claim 7 and 12 depend on claim 5, which depends on claim 1. The teachings of the references for claims 1 and 5 are described above and incorporated in its entirety for claims 7 and 12, and further described below.
Regarding claim 7, Vlieger et al further teaches the strain was added to an infant formula mix, called Friso 1, which contains, for example, GOS (galacto-oligosaccharide), zinc, and Vitamins B and D (section Study formulas).
Regarding claim 12, Vlieger et al further teaches the limitations of claim 5 and Vlieger et al further teaches the method wherein said disorders are selected from the group consisting of: neonatal colic, intestinal colic, chronic enterocolitis or chronic enterocolitis in preterm newborns and necrotizing enterocolitis, as described for claim 1, as evidenced by the increase in defecation frequency and softer stools (page 873, paragraph 2).
Claim 9 depends on claim 3, which depends on claim 1. The teachings of the references for claims 1 and 3 are described above and incorporated in its entirety for claim 9, and further described below.
Regarding claim 9, Navarro-Tapia et al further teaches tyndallized probiotics for infants and vulnerable population (page 38, paragraph 2).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to combine components from each of the prior art references in light of the advantages taught. Regarding claims 3 and 9, it would be obvious to one skilled in the art, before the effective filing date of the instant application, that viable bacteria strains can be used in newborns, but the option to use derivatives of the bacteria strains may be considered for highly vulnerable populations. Regarding claims 4 and 11-12, it would be obvious to one skilled in the art, before the effective filing date of the instant application, that the bacteria strains taught by the prior art would be reasonable probiotic candidates for the gastro-intestinal disorders claimed, as the prior art teaches them for use in treating and/or preventing these gastrointestinal disorders. Regarding claims 5 and 7, it would be obvious that these bacterial strains could be formulated with the additives claimed, and would benefit from coformulation with additional components, such as prebiotics, in light of the art teaching the synergy of prebiotic oligosaccharides and beneficial bacteria (Navarro-Tapia et al, page 16).
One skilled in the art, before the effective filing date of the instant application, would be motivated to combine these beneficial elements in known disease models to reduce the risk of adverse effects and treat gastrointestinal disorders in newborns.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success with inactivated bacteria and the additional components in the formulation since these techniques and components are not specifically beneficial to the particular bacteria strains but rather for probiotics in general.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that combining prior art elements according to known methods to yield predictable results is obvious. The prior art includes each element claimed although not necessarily in a single reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference. The use of the particular strain from Cremon et al and Biffi ‘784 claim 1 likely does not preclude the addition of the additives, the use in the claimed disease models, the use of its derivatives, and the use in certain populations, as is relevant to these claims and taught by Vlieger et al and Navarro-Tapia et al. Therefore, one of ordinary skill in the art, before the effective filing date, could have combined the elements and each element would be expected to perform, at least, the same function as it does separately.
Claim 6 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-3 and 5-16 of copending Application No. 18865784 (hereafter referred to as Biffi ‘784) in view of Vlieger et al, and further in view of Cremon et al, and further in view of Navarro-Tapia et al as applied to claims 1-5, 7, 9, 11-12 above, and further in view of Biffi WO‘458 (Biffi, A., WO2022208458A1, Inactivated strains of bacteria, such as viable but non-culturable bacteria, compositions and use thereof; Effectively filed 04/01/2021 by priority application IT102021000008300). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 6 depends on claim 5, which depends on claim 1. The teachings of the references for claims 5 and 1 are discussed above and incorporated in its entirety for claim 6 and further discussed below.
Vlieger et al further teaches the method comprising of a mixture of Lactobacillus paracasei and Bifidobacterium animalis ssp. Lactis in an infant formula (Abstract).
Vlieger et al in view of Cremon et al and further in view of Navarro-Tapia et al do not explicitly teach the instantly claimed strain of Bifidobacterium animalis ssp. Lactis.
However, Biffi WO‘458 teaches the instantly claimed strain Bifidobacterium animalis subsp. Lactis BlIBS01 DSM 33233 in a method of treating intestinal dysbiosis, inflammatory or functional gastrointestinal diseases and diseases caused by pathogenic microorganisms (Abstract and page 9).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that combining two bacteria species, Lactobacillus paracasei ssp. paracasei and Bifidobacterium animalis ssp. lactis is possible and beneficial, in light of Vlieger et at teaching this combination and the art especially recognizing the benefits of mixtures of Lactobacillus and Bifidobacterium (Navarro-Tapia et al, Abstract). It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to choose from the strain provided by Biffi WO’458 as this strain was already disclosed to treat gastrointestinal diseases.
One skilled in the art, before the effective filing date of the instant application, would be motivated to use the combination of two bacteria species known in the art and choose specific strains for the particular desired purpose based on teachings of the prior art about these strains, as both bacteria have different beneficial but compatible effects. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success in the method to treat gastrointestinal diseases as this strain was already disclosed to treat gastrointestinal diseases.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that use of a known technique to improve similar methods or products in the same way is obvious. The combination of bacteria species to improve on formulations with single bacteria species are known techniques used to improve probiotic formulations that can be applied to the relevant probiotic strains taught in the art, to arrive at the claimed invention. Although the prior art teaches the specific bacteria strains in different references, the bacteria strains and its uses are comparable and therefore, could benefit from the same improvement when combined with other probiotic bacteria, and the results would still be reasonably predictable.
Claim 6 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-3 and 5-16 of copending Application No. 18865784 (hereafter referred to as Biffi ‘784) in view of Vlieger et al, and further in view of Cremon et al, and further in view of Navarro-Tapia et al as applied to claims 1-5, 7, 9, 11-12 above, and further in view of Biffi WO’636 (Biffi, A., et al, WO2021053636A1, Bacterial strains, their compositions and their use for the treatment of gastrointestinal disorders; published 03/25/2021). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 6 depends on claim 5, which depends on claim 1. The teachings of the references for claims 5 and 1 are discussed above and incorporated in its entirety for claim 6 and further discussed below.
Vlieger et al teaches the method comprising of a mixture of Lactobacillus paracasei and Bifidobacterium animalis ssp. Lactis in an infant formula (Abstract).
Vlieger et al in view of Cremon et al and further in view of Navarro-Tapia et al do not explicitly teach the instantly claimed strain of Bifidobacterium animalis ssp. Lactis.
However, Biffi WO‘636 teaches the instantly claimed strain Bifidobacterium breve DSM 33231, Bifidobacterium breve DSM 33232, Bifidobacterium animalis subsp. Lactis DSM 33233, Lactobacillus plantarum DSM 33234, and Bifidobacterium bifidum BbfIBS0l DSM 32708 in methods for the preventive and/or curative treatment of gastrointestinal diseases, disorders or symptoms (page 1, paragraphs 1-3).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that combining two bacteria species of the Lactobacillus and/or Bifidobacterium, is possible and beneficial, in light of Vlieger et at teaching this combination and the art especially recognizing the benefits of mixtures of Lactobacillus and Bifidobacterium species (Navarro-Tapia et al, Abstract). It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to choose from the list of strains provided by Biffi WO’636 as these strains were already disclosed to treat gastrointestinal diseases.
One skilled in the art, before the effective filing date of the instant application, would be motivated to use the combination of two bacteria species known in the art and choose specific strains for the particular desired purpose based on teachings of the prior art about these strains, as both bacteria have different beneficial but compatible effects. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success in the method to treat gastrointestinal diseases as these strains were already disclosed to treat gastrointestinal diseases.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that use of a known technique to improve similar methods or products in the same way is obvious. The combination of bacteria species to improve on formulations with single bacteria species are known techniques used to improve probiotic formulations that can be applied to the relevant probiotic strains taught in the art, to arrive at the claimed invention. Although the prior art teaches the specific bacteria strains in different references, the bacteria strains and its uses are comparable and therefore, could benefit from the same improvement when combined with other probiotic bacteria, and the results would still be reasonably predictable.
Claim 8 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-3 and 5-16 of copending Application No. 18865784 (hereafter referred to as Biffi ‘784) in view of Vlieger et al, and further in view of Cremon et al, and further in view of Navarro-Tapia et al as applied to claims 1-5, 7, 9, 11-12 above, and further in view of Malfa et al (Malfa, P., et al, IT201900000801A1, Composition including non-viable probiotic bacteria and its use in therapy; published 07/18/2020). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 8 depends on claim 3, which depends on claim 1. The teachings of the references for claims 3 and 1 are discussed above and incorporated in its entirety for claim 6 and further discussed below.
Navarro-Tapia et al further teaches that derivatives of strains of bacteria, such as inactivated strains (also called paraprobiotics) could be useful for infants and vulnerable populations.
Vlieger et al in view of Cremon et al and further in view of Navarro-Tapia et al do not explicitly teach the bacterial strain is gamma irradiated.
However, Malfa et al teaches the bacterial strain is gamma irradiated.
Malfa et al teaches the disadvantages of other methods of bacteria inactivation (section State of the Art) and contrast it to inactivation by gamma rays, which maintain integrity of the bacteria cell wall, which allow it to maintain adhesive properties, which is helpful for remaining at the target site (Description of the invention). Malfa et al teaches this method can be applied to Lactobacillus paracasei (Description of the invention).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that gamma irradiated bacteria strains could be advantageous for probiotic functions over other methods of bacteria inactivation, according to the teachings of Malfa et al, and that although Malfa et al teaches their method with topical administration of the bacteria, the benefits are applicable to the gastrointestinal environment.
One skilled in the art, before the effective filing date of the instant application, would be motivated to utilize gamma irradiation to inactivate probiotic bacteria in light of the potential drawbacks taught for other common methods of bacteria inactivation.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success because this combination of bacteria species is already taught in the art to provide a multi-pronged approach to treatment. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success with gamma irradiated bacteria as it has been taught to be a suitable and perhaps better substitute for heat-inactivated probiotic bacteria or other common methods of inactivation, as it helps retain the ability for the bacteria to adhere to the intestinal wall, where it needs to work, but reduces potential undesired reactions against a live probiotic that may be especially salient in newborn subjects.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that use of a known technique to improve similar methods or products in the same way is obvious. The use of gamma irradiation to improve on probiotics inactivated by other methods are known techniques used to improve probiotic formulations that can be applied to the relevant probiotic strains taught in the art, to arrive at the claimed invention.
Claim 10 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-3 and 5-16 of copending Application No. 18865784 (hereafter referred to as Biffi ‘784) in view of Vlieger et al, and further in view of Cremon et al, and further in view of Navarro-Tapia et al as applied to claims 1-5, 7, 9, 11-12 above, and further in view of Dilli et al (Dilli, D., et al, The ProPre-Save Study: Effects of Probiotics and Prebiotics Alone or Combined on Necrotizing Enterocolitis in Very Low Birth Weight Infants, J Pediatr 2015;166:545-51; published 03/2015). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 10 depends on claim 7, which depends on claim 5, which depends on claim 1. The teachings of the references for claims 5 and 7 are discussed above and incorporated in its entirety for claim 10 and further discussed below.
Vlieger et al further teaches the strain was added to an infant formula mix, called Friso 1 (section Study formula), which contains Vitamins B and D. Vlieger et al further teaches a prebiotic-containing formula was chosen (section Study formula).
Vlieger et al does not explicitly teach at least one prebiotic is inulin.
However, Dilli et al teaches a synbiotic comprising of inulin and Bifidobacterium lactis (also known as Bifidobacterium animalis subsp. Lactis) for infants to prevent necrotizing enterocolitis (NEC). Dilli et al further teaches inulin as a prebiotic sugar that stimulate the growth and metabolic activity of beneficial bacteria. Dilli et al provides a list of exemplary prebiotic sugars including inulin and galacto-oligosaccharide (Abstract) and therefore they can be understood by one skilled in the art, before the effective filing date, that these prebiotic sugars may be suitable alternatives to choose from depending on its utility to specific bacteria probiotic. Dilli et al further teaches that both normal flora Bifidobacterium and Lactobacillus spp. colonization is delayed in premature infants (Discussion paragraph 1). As such, one would be motivated to also use inulin with Lactobacillus species, arriving at the claimed invention.
In summary, Vlieger et al teaches probiotics Lactobacillus paracasei and Bifidobacterium animalis subsp. Lactis with prebiotic galacto-oligosaccharide while Dilli et al teaches Bifidobacterium animalis subsp. Lactis with prebiotic inulin but teaches inulin and galacto-oligosaccharide as prebiotics (Abstract). It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that the galacto-oligosaccharide could be substituted with inulin as the prebiotic for formulations comprising of Lactobacillus paracasei as both sugars are used to stimulate probiotic growth.
One skilled in the art, before the effective filing date of the instant application, would be motivated to try the inulin as a prebiotic for Lactobacillus paracasei, as Dilli et al teaches that Lactobacillus and Bifidobacterium are two normal bacterial flora (Discussion, paragraph 1), and therefore, are often probiotic candidates administered together, as taught by Vlieger et al. As such, since inulin is shown to work for Bifidobacterium, it would be useful to try this with Lactobacillus to see if inulin can be used for both probiotics, which could be especially useful in probiotic combinations.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success since these common prebiotics are chosen for their ability to be metabolized by many bacterial species.
KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007), discloses that choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success is obvious. Dilli et al teaches a finite number of identified predictable potential solutions (i.e. prebiotics) that could be useful with the probiotic bacteria. One skilled in the art, before the effective filing date of the instant application, could have pursued the known potential prebiotics with reasonable expectation of success with the two common species of probiotics.
Although Biffi ‘784 claims 2-3, 5-9, and 11-16 are not explicitly referred to in this rejection, they provide additional details that may be relevant to the instantly claimed invention and thus are acknowledged here for the record.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BONIRATH CHHAY whose telephone number is (571)272-0682. The examiner can normally be reached Mon-Thu 8AM-5PM EST.
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, Daniel Kolker can be reached at (571) 272-3181. 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.
/B.C./Examiner, Art Unit 1645
February 19, 2026
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1645