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 .
DETAILED ACTION
Preliminary amendment filed on 10/26/2023 is acknowledged. Claims 1-19 were cancelled and claims 20-33 were newly added. Claims 20-23 are pending in the instant application and are examined on the merits herein.
Priority
This application is a National Stage Application of PCT/EP2022/061824, filed on 05/03/2023 and claims foreign priority to European Patent Office (EPO) 21171884.6 filed on 05/03/2021.
Information Disclosure Statement
The information disclosure statement (IDS) dated 10/26/2023 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, the IDS document has been placed in the application file and the information therein has been considered as to the merits.
Claim Objections
Claim 20 is objected to because of the following informalities: the term “galactosyllactose” is repeated twice on line 5. 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 23, 26,30, and 33 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.
Regarding claims 23, 26,30, and 33, the term “preferably” renders the claims indefinite because it is unclear whether the limitations after said term are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 20-33 are rejected under 35 U.S.C. 112(a), because the specification, while being enabling for decreasing the B cell adaptive immune response to vaccination with an antigen that is derived from a virus in a subject, the method comprising administering galacto-oligosaccharides to a subject, it does not reasonably provide enablement for preventing and/or ameliorating the B cell adaptive immune response to vaccination with an antigen that is derived from a virus in a subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
With respect to the claimed method, attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
All of the Wands factors have been considered and those most relevant to the cited claims are discussed below.
Nature of the invention: The invention is drawn a method for preventing and/or ameliorating a food contaminant induced decrease of the B cell adaptive immune response to vaccination with an antigen that is derived form a virus in a subject, the method comprising administering galacto-oligosaccharides to the subject.
Relative skill of those in the art: The relevant art is pharmaceutical formulations, which is a mature art where practitioners receive specialized training and earn advanced degrees during the course of their study. There is a voluminous amount of published material describing research, best practices and practical application of compositions and techniques to the medical field. The relative skill of those in the art is high.
Breadth of claims: The claims are broad with respect to the concept of prevention. The full scope of the instant claims covers the entire definition of treatment and prevention as well any adverse effect from a decrease of the B cell adaptive immune response to vaccination with an antigen that is derived from a virus in a subject. The specification defines “prevention” as referring to “reducing the risk of” or “reducing the severity of” (specification page 13). The full scope of the claims encompasses the entire definition of tertiary prevention, which covers reducing the occurrence of or eliminating a symptom or condition. The term “prevention” is assumed to take on the customary meaning known to those skilled in the art. Specifically, “prevention” is defined according to the Institute for International Medical Education (Wojtczak, 2002) as: the goals within the field of medicine to promote health, to preserve health, to restore health when it is impaired, and to minimize suffering and distress. Customarily prevention is sub-classified as primary (the protection of health by personal and community wide effects), secondary (the measures available to individuals and populations for the early detection and prompt and effective intervention to correct departures from good health) and tertiary (the measures available to reduce or eliminate long-term impairments and disabilities, minimize suffering caused by existing departures from good health, and to promote the patient's adjustment to irremediable conditions). Tertiary prevention is most relevant as used in the context of the instant invention. Thus, the intent of the method, as interpreted by a skilled practitioner of the medical or pharmaceutical arts, would include that which reduces the occurrence of, or eliminates, the induced decrease of the B cell adaptive immune response to vaccination.
Amount of guidance/Existence of working examples: The instant specification provides experimental results administration of a diet rich in a Galacto-oligosaccharide (GOS) comprising beta-3’-GL to DON-exposed mice (instant specification example 2, page 17). The results showed that the DON induced significant reduction in B cells and that the addition of GOS to DON-contaminated diets significantly increase the percentage of B cells in the spleen and was able to restore the effect of DON (instant specification, Table 3, page 17). However, the experiment did not compare the DON-contaminated group administered GOS to a non-DON contaminated control group that was also administered GOS to compare effect of GOS on B cells in order for one of ordinary skill in the art to determine if the GOS prevented the induced decrease of the B cell adaptive immune response or if GOS increased the B cells on their own.
State of the prior art/Predictability or unpredictability of the art: Akbari et al. (The Journal of Nutrition, published 05/27/2015, see IDS dated 10/26/2023) is drawn to the study of galacto-oligosaccharides (GOS) protecting the intestinal barrier after a challenge with the mycotoxin deoxynivalenol (DON)(title). Akbari showed that while 2% GOS induced a protective effect on the DON-induced impaired monolayer integrity, it was less pronounced than in experiments where GOSs were present at both sites and during the entire exposure period. Further, neither 0.5% GOSs nor 1% GOSs were effective (Table 1). Co-incubation of GOSs and DON for 24h did not counteract the DON-induced intestinal barrier disruption (page 1607). Therefore, it can be concluded that any amount of GOS cannot prevent a DON-induced effect.
Quantity of experimentation: One of ordinary skill in the art would have to conduct a myriad number of experiments comprising trial and error administration of the claimed composition to an infant or young child to determine if the claimed compositions can be used in the fully claimed scope to prevent a food contaminant induced decrease of the B cell adaptive immune response to vaccination. Further, it is difficult to know who would get exposed to a food contaminant that would induce a decrease of the B cell adaptive immune response to vaccination. Genetech, 108 F.3d at 1366, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors as discussed above, e.g., the breadth of the claims, the amount of guidance provided, the state/unpredictability of the art and the lack of working examples, one of skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims, with no assurance of success. Claims 21-26 and 29-33 are rejected for being dependent on a rejected claims base.
Claim Rejections – 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 20-33 are rejected under 35 U.S.C. 103 as being unpatentable over Garssen et al. (US 9,782,422 B2, published 10/10/2017, see PTO-892), Stahl et al. (US 8,591,919 B2, published 11/26/2013, see PTO-892), and Frese (WO 2019/246316 A1, published 12/26/2019, see PTO-892).
Garssen is drawn to compositions comprising a non-digestible oligosaccharide for the treatment of a trichothecene mycotoxin exposure associated condition. The non-digestible oligosaccharide may comprise a short chain galacto-oligosaccharide (abstract). The non-digestible oligosaccharide may comprise galacto-oligosaccharides
with β(1,4), β (1,3) and/or β (1,6) glycosidic bonds and a terminal glucose (abstract). A galacto-oligosaccharide with β (1,3) glycosidic bonds and a terminal glucose would be β (1,3) -galactosyllactose. The trichothecene mycotoxin exposure associated condition may be associated with exposure to deoxynivalenol (abstract). Garssen teaches that the condition may be selected from a list of including modulation of serum immunoglobulin levels or immunosuppression (claim 9). Garssen teaches that trichothecenes are acutely cytotoxic and strongly immunosuppressive (column 13). Garssen teaches that the use of oligosaccharides to restrict the pathological effects of DON related to intestinal epithelial is promising for mycotoxin exposure intervention (columns 24-25). Garssen teaches that trichothecenes occur in cereal grains and in derived products such as breakfast cereals (column 14). Garssen teaches that the non-digestible oligosaccharide may be present in the composition at any suitable concentration such as 0.01g-1.0g per 100 mL in a liquid formula (column 12).
Regarding instant claims 24 and 31, Garssen teaches that the non-digestible oligosaccharide composition may comprise a cereal component.
Regarding instant claims 23 and 30, Garssen teaches that the composition may be administered to babies, infants which are in the adaptation period to solid food, toddlers, children, teenagers, or adults (column 22).
Regarding instant claims 26 and 33, Garssen teaches that the compositions may comprise an infant and/or toddler nutrition, such as an infant and/or toddler formula (column 17 and claim 17).
Garssen does not teach the administration of the composition for inhibiting a food contaminant induced decrease of the B cell adaptive immune response to vaccination. Garssen does not teach that the composition comprises at least 20% beta 1,3’ -galactosyllactose. Garssen does not teach that the composition comprises at least 1 wt% galacto-oligosaccharides based on dry of the nutritional composition.
Stahl is drawn to a nutritional composition comprising at least two different beta-galacto-oligosaccharides (BGOS) A and B wherein the majority of linkages between two galactose residues in BGOS A are beta 1,4 and/or beta 1,6, and the majority of linkages between two galactose residues in BGOS B are beta 1,3 (abstract). Stahl teaches that the BGOS B have a structure of Galn-Glu and/or Galm, with n=2-6 and m=2-6. Stahl teaches that a Gal-Gal-Glu may have a % linkage between the two galactose residues up to 100% beta 1,3. A Gal-Gal-Glu with a beta 1,3 linkage is a beta 1,3’-galactosyllactose (column 2). The mixture of BGOS had an improved effect on stimulating the immune system (column 1) and an increased Th1 response was observed which was indicative of an increased vaccination response (column 1). Stahl teaches the method of stimulating the immune system comprising administering to a human subject the composition comprising GOS wherein the human subject is a human infant (claims 9 and 10). Stahl teaches that the composition may comprise a sum of the BGOS up to 20 wt. % based on dry weight (column 3).
Frese is drawn to novel structures in mare’s milk that may be synthesized or purified for use in a variety of applications related to the gut microbiome and mammalian health (abstract). Frese teaches a composition comprising Gal(β l-3)Gal(β -4)Glc (claim 1). Gal(β l-3)Gal(β -4)Glc is beta 1,3’-galactosyllactose. Frese teaches that the oligosaccharide may be provided in its own composition or as part of a food composition. The composition may be administered to an infant, an adolescent, an adult, or a geriatric adult (paragraph 0055). The treatment may be designed to stimulate the immune system for the purpose of improving host defense, including but not limited to improving mucus production and/or reducing mucus degradation, B cell responsiveness and/or expanding or altering the T Regulatory and Helper T cell profile. The composition may result in induction of oral tolerance and improved vaccine efficacy (paragraph 0049). The composition may be used on a mammal to treat vaccine responsiveness (paragraph 0050).
It would have been prima facie obvious to combine the teachings of Garssen, Stahl, and Frese before the effective filing date of the invention by applying the method of treating a mycotoxin exposure associated condition with a composition comprising a galacto-oligosaccharide as taught by Garssen to inhibit an induced decrease of the B cell adaptive immune response to vaccination as taught by Frese to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to apply the method of treating a mycotoxin exposure associated condition with a composition comprising beta 1,3’-galactosyllactose because Garssen teaches that a composition that may comprise beta 1,3’-galactosyllactose may be used to treat a mycotoxin exposure associated condition and that the condition may be immunosuppression, Stahl teaches that BGOS had an improved effect on stimulating the immune system and an increased vaccination response, and Frese teaches that a composition comprising beta 1,3’-galactosyllactose may stimulate B cell responsiveness and improve vaccine efficacy. One of ordinary skill in the art would have a reasonable expectation of success because Garssen teaches that a composition that may comprise beta 1,3’-galactosyllactose may be used to treat a mycotoxin exposure associated condition and that the condition may be immunosuppression, Stahl teaches that BGOS had an improved effect on stimulating the immune system and an increased vaccination response, and Frese teaches that a composition comprising beta 1,3’-galactosyllactose may stimulate B cell responsiveness and improve vaccine efficacy.
It would have been prima facie obvious to combine the teachings of Garssen, Stahl, and Frese before the effective filing date of the invention by optimizing the composition comprising beta 1,3’-galactosyllactose for the treatment of a trichothecene mycotoxin exposure associated condition to comprise at least 20% of the galacto-oligosaccharides to be beta 1,3’-galactosyllactose as taught by Stahl to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to optimize the composition to comprise at least 20% of the galacto-oligosaccharides to be beta 1,3’-galactosyllactose because Stahl teaches that the composition may comprise up to 100% beta 1,3’-galactosyllactose. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). (MPEP § 2144.05(I)) Moreover, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). (MPEP § 2144.05(II)) “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003).
Regarding instant claims 25 and 32, it would have been prima facie obvious to combine the teachings of Garssen, Stahl, and Frese before the effective filing date of the invention by optimizing the composition to compromise at least 1 wt% galacto-oligosaccharides based on dry weight of the nutritional composition in the composition as taught by Stahl to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to optimize the amount to compromise at least 1 wt% galacto-oligosaccharides based on dry weight of the nutritional composition because Stahl teaches that the composition may comprise a sum of the BGOS up to 20 wt. % based on dry weight. One of ordinary skill in the art would have a reasonable expectation of success by the amount to compromise at least 1 wt% galacto-oligosaccharides based on dry weight of the nutritional composition taught by Stahl because Stahl teaches that the composition may comprise a sum of the BGOS up to 20 wt. % based on dry weight. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). (MPEP § 2144.05(I)) Moreover, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). (MPEP § 2144.05(II)) “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003).
Conclusion
No claims allowed.
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/SAMANTHA LYNN SCHACHERMEYER/Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693