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
This application is a CON of 18/267969 filed June 16, 2023, with provisional application 63/127936, filed December 18, 2020.
Applicant’s submission of claims filed August 5, 2024 is acknowledged.
Claims 1-24 are pending.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 3, 11, 14, 18-20, and 21 are objected to because of the following informalities:
Claim 3, lines 1-2, need to be changed to “Lactobacillus reuteri Bifidobacterium animalis subsp. lactis
Claim 11, line 2, “GARS-3” needs to be defined before using the acronyms in the claim (RRB, SI, SC, ER, CS, MS).
Claim 14, line 3, needs a comma between “10 weeks [,] 11 weeks”.
Claim 18, line 1, “wherein the microbiome composition of the subject…” needs to be changed to “wherein the subject’s microbiome…” to reduce redundancy in claim language.
Claims 19 (lines 1 & 3) and 21 (line 1), “where in the difference comprises” needs to be changed to “wherein the microbiome difference comprises” to maintain claim language consistency.
Claim 19, line 1, “wherein difference comprises…in one of more” needs to be changed to “wherein the microbiome difference comprises…in one or more” for grammatical error.
Claim 20, lines 2-3, “in one of more” needs to be changed to “in one or more” for grammatical error.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating children with Prader-Willi syndrome (PWS) by administering an effective amount of B. animalis subsp. lactis (B. lactis) strain BL-11 and/or Lactobacillus reuteri strain LR-99 to the child for at least about 3 weeks to about 12 weeks, does not reasonably provide enablement for a method of treating any type of subject with PWS by administering an effective amount of a probiotic comprising any type of bacteria for any amount of time/dosing schedule. 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.
The breadth of the claims:
Claims 1-21 are drawn to a method of treating PWS by administering an effective amount of a probiotic to the subject, wherein the probiotic can comprise different genera recited in claim 2. Claims 5-12 and 17 are drawn to symptoms or conditions the subject is suffering from, such as obesity, short stature, social deficits, fine motor abnormalities, developmental delay, and abnormal behavioral characteristics, and assessments to determine the effectiveness of the probiotic at alleviating these symptoms/conditions. The Specification discloses PWS is recognized as the most common genetic cause of life-threatening childhood obesity. The breadth of the claims encompass any ‘probiotic’ administered to any subject with or at risk of PWS at any time point/dosing schedule. The Specification discloses ‘probiotic’ refers to organisms, generally bacteria, which are considered to be beneficial rather than detrimental to their animal host. The Specification discloses exemplary probiotic bacteria include, without limitation Lactobacillus, sp., Saccharomyces, sp., Bifidobacterium, sp., Streptococcus, sp., Escherichia coli., Bacillus, sp., and Eubacterium hallii, wherein L. reuteri and B. lactis have been shown in the prior art to reduce inflammation and have anti-obesity effects. The Specification discloses the ‘subject’, particularly a mammalian subject, for whom diagnosis, prognosis, or therapy is desired. The Specification discloses a therapeutically effective amount is achieved by administering multiple therapeutically effective doses, e.g., over the course of a day, several days, a week, several weeks, months, or years.
The nature of the invention:
The nature of the invention relies upon administering an effective amount of a probiotic to a subject with or at risk of PWS.
The state of the prior art:
Whether the specification would have been enabling as of the filing date involves consideration of the nature of the invention, the state of the prior art, and the level of skill in the art. The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed. See MPEP § 2164.05(b). The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification.
A thorough review of the patent and non-patent literature indicates that the state of the art demonstrating treatment of any type of subject with or at risk of PWS with any type of probiotic is limited and variable. A recent review by Ramon-Kruel et al. (J. Clin. Med. 2021, 10, 5328, pgs. 1-9) discloses there have been four randomized controlled clinical studies of treatments targeting the gut microbiome in PWS, wherein L. reuteri and B. lactis were only used as single strains in the probiotic, and was administered only to children with PWS from 4-12 weeks (pg. 5, Table 2). Lalonde et al. (Current Neuropharmacology, 2023, 21, pgs. 2481-2486) discusses probiotic influence on motor skills, and discloses a randomized trial wherein B. infantis 96579 + B. lactis BB-12 15954 + S. thermophilus TH-4 15957 had no effect on the Gross Motor Function Classification System score, the Bayley-III Motor Composite Scale, or the Movement Assessment Battery for Children in preterm children at 2-5 years of age (pg. 2481, sec. 2.1).
A review by Loy et al. (Childhood Obesity, 2023, vol. 19, no. 3, pgs. 146-159) discusses probiotic use in children and adolescents with overweight or obesity, and discloses controversial data highlight that the connection between microbiota composition and excess weight is very complex, for example, data show positive correlation between Lactobacillus reuteri and obesity, whereas Bifidobacterium animalis has been associated with a lower BMI (pg. 146, col. 1, para 3). Loy et al. discloses six studies showing an association between probiotic use and reduction in BMI, however seven studies did not show BMI improvement with probiotic use, wherein the studies used different species and doses of the probiotic, which ranged from 8 weeks to 9 months in children ages 2-19 (pg. 148, col. 2, para 5). Loy et al. discloses the scoping review found no evidence for the use of probiotics in the prevention of obesity, and heterogeneous evidence for the use of probiotics in the treatment of obesity in children and adolescents with overweight or obesity and those with weight-related conditions (pg. 154, col. 1, para 1). .
Thus, a review of the prior art does not find a correlation between PWS treatment and administering the full scope of any probiotic to any type of subject with or at risk of PWS at any timepoint.
The level of one of ordinary skill and predictability in the art:
While the level of one of ordinary skill practicing said invention would be high, the level of predictability is considered variable as evident in the prior art discussed above and is not considered to provide sufficient enablement to practice the claimed invention. Because the state of the prior art does not provide evidence of the degree of predictability that methods for treating PWS in any type of subject by administering any type of probiotic at any timepoint/dosing schedule, one of ordinary skill in the art would look for guidance or direction in the instant specification.
“The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability.” (MPEP 2164.03). In the instant case, the various probiotics, subjects, and timepoints/dosing schedules that fall within the scope of “treating a subject diagnosed with or at risk of PWS by administering an effective amount of probiotic to the subject” would require different treatment methods. For instance, administration of L. reuteri in obese adults would have a negative effect on BMI, whereas administration of B. animalis would lower BMI in adults, as evidenced by Loy et al. (pg. 146, col. 1, para 5).
The amount of direction provided by the inventor and existence of working examples:
The instant application describes administering L. reuteri (strain LR-99) to study participants recruited through the PWS Care & Support Center, and had to meet the following criteria: genetic confirmation of PWS, no prior probiotic use for at least 4 weeks, no planned changes in medications or psychosocial interventions, and were excluded if they had other known genetic disorders, or if they were pregnant or breast-feeding. Each dosage of LR-99 contained 3 x 1010 CFU and were administered twice a day for 12 weeks, wherein the children’s ages ranged from 6 months to 22 years. The specification also describes a similar study administering B. lactis (strain BL-11) to a similar participant cohort.
The working embodiments do not describe any other type of probiotic used in the treatment of any other type of subject (such as an adult) with PWS at any other timepoint/dosing schedule, other than administering twice a day at a dose of 3 x 1010 CFU for a 12 week period. While the MPEP 2164.02 states the specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
The prior art is undeveloped for the role that administering any type of probiotic at any timepoint/dosing schedule to any type of subject diagnosed with PWS, and given the broad scope of the claims and the different conditions encompassed, it is unpredictable if administering any type of probiotic at any timepoint/dosing schedule would reasonably treat any type of subject diagnosed with PWS. The specification does not provide sufficient guidance on treating subjects diagnosed with PWS by administering the full scope of all probiotics, subjects, and/or timepoints/dosing schedules. Rather the specification describes examples of treating children diagnosed with PWS by administering L. reuteri (strain LR-99) or B. lactis (BL-11) twice a day for 12 weeks. The prior art also does not provide additional guidance to enable treating the full scope of the claims.
Therefore, due to the unpredictability in the art with respect to treating PWS with the full scope of probiotics, subject type, and timepoints/dosing schedules, one would have to engage in experimentation that is not reasonable in order to determine which of the various probiotics, subjects, and timepoints/dosing schedules could be used in the treatment of PWS.
Without further guidance, one of skill in the art would have to practice a substantial amount of trial-and-error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention.
Claims 1-3, 5-7, 13-16, 18, and 21-23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-3, 5-7, 13-16, 18, and 21 recite a method a method for treating a subject diagnosed with or at risk of PWS comprising administering an effective amount of a probiotic to a subject, wherein the probiotic comprises Lactobacillus sp. and Bifidobacterium animalis subsp., and recites particular symptoms or conditions the subject is suffering from, treatment schedules, and microbiome changes in the subject. Claims 22-23 recite a composition comprising an effective amount of one or more probiotics and a growth hormone, wherein the composition comprises Lactobacillus sp. and a growth hormone. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant case, the specification merely gives working examples of compositions comprising B. lactis BL-11 strain or L. reuteri LR-99 strain used in a study administered to children with or at risk of PWS, and are the only species whose complete structure is disclosed. While the genus encompasses a large number of variants that have the same activity as pancreatic enzymes in kind and the genus encompasses a large number of variants that have a different structure, the specification does not describe the complete structure of a representative number of species of the large genus of probiotics, or functional equivalents thereof. Additionally, the specification does not describe the complete structure of a representative number of species of the large genus of growth hormones, only describing human growth hormone as being shown to improve height, cognition, and motor function when administered early in development of PWS patients [0071].
Next, then, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics, specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case, the only other identifying characteristic of a probiotic is generally bacteria, which are considered to be beneficial rather than detrimental to their animal host, and points to exemplary probiotic bacteria including, without limitation Lactobacillus, sp., Saccharomyces, sp., Bifidobacterium, sp., Streptococcus, sp., Escherichia coli., Bacillus, sp., and Eubacterium hallii [0074-0075], as well as inducing significant favorable gut microbiome composition changes that lead to reduced fat deposit via insulin and calcium signaling regulation, and improved mental health via gut brain axis [0083]. Such a broad limitation cannot be an identifying characteristic for the claimed diverse genus of probiotics since by Applicant’s definition of probiotic species or functional equivalent thereof all members of the claimed genus will have that characteristic. Further, no identifying characteristics of the growth hormones are disclosed, only disclosing human growth hormone, but does not indicate synthetic or recombinant forms of such.
The inventions of claims 5-7, 13-16, 18, and 21 require the use of the inventions of claims 1-3, and therefore are likewise rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement.
Applicant’s attention is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or Pre-AIA 35 U.S.C. 112, first paragraph, "Written Description" Requirement (MPEP2163).
In conclusion, Applicant’s disclosure of the species of an effective amount of a composition comprising one or more probiotics (Lactobacillus sp.) and growth hormone of the claimed broad genus is not deemed sufficient to reasonably convey to one skilled in the art that Applicant was in possession of the claimed broad genus at the time the application was filed. Thus, it is concluded that the written description requirement is not satisfied for the claimed genus.
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 2, 5-12, and 21 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 2 recites “wherein the probiotic comprises one or more of a Lactobacillus, sp., Saccharomyces, sp., Bifidobacterium, sp., Bacillus, sp., and Eubacterium hallii.”. This claim limitation appears to be a Markush grouping, but it is unclear if the ‘one or more of’ clause is referring to one or more different genera or species that is included in the probiotic. The Examiner interprets this limitation as a Markush grouping and suggests Applicant amend to “where in the probiotic comprises one or more species selected from the group consisting of Lactobacillus, sp., Saccharomyces, sp., Bifidobacterium, sp., Bacillus, sp., and Eubacterium hallii.” to obviate this rejection. Similarly claim 19 recites ‘a decrease in one or more of Escherichia-Shigella, Porphyromonas, and Ruminococcus torques…”, which is indefinite.
The term “decreased” in claim 5 is a relative term which renders the claim indefinite. The term “decreased” is not defined by the claim, the specification does not provide a standard of measurement of symptoms or conditions for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Based on the specification, the decrease of symptoms or conditions are measured based on various metrics, such as BMI, height, and psychology scores. It is unclear how the subject would ‘decrease’ a condition of social deficits, fine motor abnormalities, development delay, and abnormal behavioral characteristics.
Claim 9 recites the limitation "the subject is suffering from varying severities of psychopathology" in lines 1-2. It is unclear if ‘the subject’ is in addition to suffering from one or more of the symptoms or conditions listed in claim 5, or if the subject is only suffering from psychopathology. The Examiner interprets the subject is suffering from psychopathology in addition to one or more conditions listed in claim 5.
Claims 9 and 12 recite “Clinical Global Impression-Improvement (CGI-I)” and then in claim 9 also recites “the baseline CGI severity” and in claim 12 recites “…and severity (CGI-S)”. As the claims are written, it is unclear if ‘CGI-I’ and ‘CGI-S’ are two separate measures, or ‘CGI-S’ is a subset of ‘CGI-I’. Based on the Specification, CGI-I and CGI-S are two separate measurements of the Clinical Global Impression assessment. The Examiner recommends amending to improve clarity in claim language.
Claims 8-9 recite “…before treatment by B. lactis.” and claims 10-11 recite “…before treatment by L. reuteri”. There is insufficient antecedent basis for these claim limitations, as the independent claim 1 only recites ‘a probiotic’, therefore is indefinite. Similarly claims 19-20 recite “decrease/increase in one or more of…by L. reuteri.”, which lacks antecedent basis.
Claim 18 recites “wherein the difference comprises a significant positive association of Rothia against RRB.” It is unclear what a ‘significant positive association’ of a bacteria is ‘against restrictive, repetitive behaviors (RRB)’, and how one of ordinary skill in the art can ascertain the metes and bounds of the claim. Based on the Specification, Rothia prevalence in the microbiome is positively correlated with RRB, thus is how the Examiner interprets the claim. It is further unclear how the ‘difference’ of the microbiome of the subject after treatment comprises a positive correlation of Rothia to RRB.
Claims 6-7 and 13-17 are rejected as being dependent on an indefinite claim.
Claim Interpretation
For claims 8-12 and 19-20, the Examiner rejects the limitations ‘by L. reuteri’ or ‘by B. lactis’ as indefinite as described above, and is therefore interpreting the probiotic recited in claim 1 to encompass any microorganism that would result in the desired effects recited in the claims.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2, 5-7, 13-16, and 18-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Amat-Bou et al. (Nutrients, 2020, 12, 3123, pgs. 1-15, published: 13 October 2020, cited in IDS filed 10/14/2024, hereinafter “Amat”).
Regarding claims 1, 2, and 13-15, Amat teaches effects of Bifidobacterium animalis subsp. lactis BPL1 supplementation in children and adolescents with Prader-Willi Syndrome (PWS) (title). Amat teaches daily administration of BLP1 to participants for a 12-week period, wherein 100mg of BPL1 contained 1010 CFUs, which anticipates the claims (abstract).
Regarding claim 5, Amat teaches PWS is a rare genetic disorder characterized by a wide range of clinical manifestations, including altered body composition, hyperphagia, and severe behavioral problems (pg. 2, para 1). Amat teaches conditions develop as hyperphagia, morbid obesity if uncontrolled, and mental health problems, including anxiety and social problems (pg. 2, para 1). Amat teaches a randomized crossover design with a 1:1 allocation ratio was chosen for this study, wherein participants suffered a wide range of symptoms/conditions, including obesity and mental health problems, which anticipates the claim (pg. 2, sec. 2.1). Amat teaches a significant decrease in abdominal fat mass after BPL1 supplementation compared to placebo group on subjects older than 4.5 years, which anticipates the claim (pg. 7, sec. 3.3).
Regarding claims 6-7, Amat teaches for evaluating mental health problems, Childhood Behavioral Check List (CBCL) was used, which is a component of Achenbach System of Empirically Based Assessment (ASEBA), that tests measures of emotional and behavioral problems using over 100 items, grouped into Internalizing, Externalizing, and Total scales (pg. 4, sec. 2.5). It consists of 8 subscales (Anxious/depressed, Withdrawn/depressed, Somatic complaints, Social problems, Thought problems, Attention problems, Rule-breaking behavior, and Aggressive behavior), which anticipates claim 7 (pg. 4, sec. 2.5). Amat teaches Bifidobacterium animalis subsp. lactis strain BPL1 induced modest but significant improvements (decrease in test score) in withdrawn/depression symptoms, and trend toward improvement in attention problems compared to placebo, which anticipates claim 6 (pg. 9, para 1, Table 4).
Regarding claim 16, Amat teaches the probiotic was administered to participants that were genetically confirmed PWS diagnosis, age between 2 to 19 years, and being on a stable diet and medication regimen for at least two months before enrollment, with special attention to growth hormone (GH) therapy and metformin use, which anticipates administered an additional therapeutic (pg. 3, sec. 2.2).
Regarding claims 18-19, Amat teaches the microbiome of the participants changes after treatment, with B. animalis abundance showing the greatest difference between probiotic and placebo treatment, which anticipates the claims (pg. 7, Fig. 2). Amat teaches a slight decrease in Ruminococcus torques between the placebo and BPL1 group, as well as a slight decrease between before and after treatment (Supplemental Table 1).
Regarding claim 20-21, Amat teaches decrease in Rothia between placebo and BPL1 groups, as well a slight decrease in abundance before and after treatment (Supplemental Table 1). Amat does not explicitly teach an increase in one or more of Bifidobacterium, Lactobacillus, Faecalibacteria, Roseburia and Alistipes, or a significant positive association between Rothia and RRB, however, the decrease in Rothia abundance and decrease in autism-like behavior (including repetitive and compulsive behaviors) (pg. 11, para 1) and the same method step taught by Amat inherently anticipates the claims. A recitation of an advantageous property or desired outcome of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to distinguish the claimed invention from the prior art. In this case, administering an effective amount of a probiotic to the subject appears to be capable decreasing Rothia in the microbiome and the RRB Prader-Willi symptom.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 3, 4, 8 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Amat as applied to claims 1-7, 13-16, 18-19 and 21 above, and further in view of Minami et al. (WO 2019189408 A1, cited in IDS filed 10/14/2024, hereinafter “Minami”).
Amat teaches effects of Bifidobacterium animalis subsp. lactis (BPL1) supplementation in children and adolescents with Prader-Willi Syndrome (PWS) (title). Amat teaches daily administration of BLP1 to participants for a 12-week period, wherein 100mg of BPL1 contained 1010 CFUs (abstract). Amat teaches a significant decrease in abdominal fat mass after BPL1 supplementation compared to placebo group on subjects older than 4.5 years (pg. 7, sec. 3.3).
Amat does not teach the BPL1 was administered twice per day at a dose of about 3 x 103 CFU, and an obesity measurement comprising BMI, wherein the BMI is lower after treatment with L. reuteri than before treatment.
Regarding claims 3, 4 and 8, Minami teaches a method and composition that are effective in obesity treatment using probiotics such as bifidobacteria and lactobacilli (abstract). Minami teaches body-mass index (BMI) as the measurement for obesity, wherein the "obesity preliminary group" refers to mild obesity having an BMI value of 25 or greater and less than 30, and "obesity" refers to obesity having an BMI value of 30 or greater, which meets the limitation in claim 8 (pg. 15, para 1). Minami teaches the probiotic can comprise B. animalis subsp. lactis and L. reuteri, but is not particularly limiting to the species (pg. 11, para 11, pg. 12, para 1). Minami teaches the values of the test group were lower than the values of the control group, and among them, the body fat percentage and the body fat mass were detected as significant differences, which meets the limitation in claims 8 and 17 (pg. 17, para 3).
Regarding claim 17, Minami teaches the probiotic dose can be divided from once a day to multiple times per day at a dose of 1 x 103 CFU to 1 x 1012 CFU, which meets the limitations of 3 x 103 CFU and twice per day in claim 17 (pg. 7, para 2-4).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Amat’s method of treating PWS with a probiotic comprising B. lactis taught by Amat and L. reuteri taught by Minami, and administer the probiotic multiple doses a day at a dose of 1 x 103 CFU to 1 x 1012 CFU, and measure BMI to evaluate the treatment effect on obesity as taught by Minami with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to optimize the treatment dosage for effective anti-obesity effects, and also use a common, routine measurement BMI to track the probiotic’s effectiveness.
Claims 9 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Amat as applied to claims 1-7, 13-16, 18-19 and 21 above, and further in view of Dangles et al. (US2017/0326200A1, previously cited in IDS filed 10/14/2024, hereinafter “Dangles”).
Amat teaches mental health problems were evaluated in the subgroup of participants older than 6 years of age, specifically, BPL1 induced modest but significant improvements (decrease in test score) in withdrawn/depression symptoms, and a trend toward improvement in attention problems compared to placebo, the rest of the symptom dimensions evaluated did not reach statistical significance, although several showed numerical decreases (pg. 9, sec. 3.5, Table 4).
Amat does not teach varying severities of psychopathology are measured by Clinical Global Impression-Improvement (CGl-I), nor the CGI-I and CGI-S are statistically improved after treatment with B. lactis.
However, Dangles teaches methods of treating PWS, and evaluating varying severities of psychopathology as measured by Clinical Global Impression-Improvement (CGl-I) which meets the limitation of claim 9 (abstract, para 115). CGI rating scales are commonly used measures of symptom severity, treatment response and the efficacy of treatments in treatment studies of subjects with psychiatric, neurological or behavioral disorders (para 115). Dangles teaches the CGI scale is a 7-point clinician rating of illness severity (CGI-S; 1=normal, not at all ill, 7=among the most extremely ill patients), at the beginning of the trial and a 7-point clinician rating of improvement of patient condition, during and at the end of the trial (CGI- I; 1=very much improved since baseline, 7=very much worse from baseline), wherein the CGI-S scale was completed during Visit 1, and the CGl-I scale was completed during Visit 4 and on Day 8 of the trial (para. 116). Dangles teaches at Day 8 and Day 15, the CGI scores were statistically improved in the treatment method (pg. 9, Table 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of treating PWS with a probiotic comprising B. lactis as taught by Amat by adding an evaluation of subjects suffering from varying severities of psychopathology measured by CGI-I before and after treatment, as taught by Dangles. One of ordinary skill in the art would have been motivated to include this assessment of improved mental health due to administration of the B. lactis, as this is a common assessment used in methods for treating PWS as disclosed in Dangles. Furthermore, it would have been obvious to modify the Amat method of assessing PWS treatment by using CGI-I taught by Dangles for the purpose of observing changes in PWS subjects. There would have been a reasonable expectation of success since both Amat and Dangles are in the same field of endeavor, a method of treating PWS.
Claims 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Amat as applied to claims 1-7, 13-16, 18-19 and 21 above, and further in view of Kong et al. (Frontiers in Psychiatry, 2020, Vol. 11, Article 594934, pgs. 1-8, previously cited in IDS filed 10/14/2024, hereinafter “Kong”).
Regarding claim 10, Amat teaches mental health problems were evaluated in the subgroup of participants older than 6 years of age, specifically, BPL1 induced modest but significant improvements (decrease in test score) in withdrawn/depression symptoms, and a trend toward improvement in attention problems compared to placebo, the rest of the symptom dimensions evaluated did not reach statistical significance, although several showed numerical decreases (pg. 9, sec. 3.5, Table 4).
Amat does not explicitly teach developmental delays are measured by Ages and Stages Questionnaires, 3rd Edition (ASQ-3) score for one or more of communication, gross motor function, fine motor function, problem-solving, and personal-social interaction.
However, Kong teaches early screening and risk factors of Autism Spectrum Disorder (ASD) in a large cohort of Chinese patients with PWS (title). Kong teaches developmental delays are measured by Ages and Stages Questionnaires, 3rd Edition (ASQ-3) score for one or more of communication, gross motor function, fine motor function, problem-solving, and personal-social interaction (pg. 2, col. 2, para 5). The ASQ-3 was handed or mailed to the parents of the 103 participants younger than 36 months old, and is one of the most widely available development, communication, and behavior screening tools for young children (pg. 2, col. 2, para 5). The ASQ-3 provides parents with information about the developmental status of their young child across five developmental domains: communication, gross motor, fine motor, problem-solving, and personal-social (pg. 2, col. 2, para 5).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of treating PWS with a probiotic, as taught by Amat, by adding an evaluation of the patient’s progress of developmental delays with the ASQ-3 assessment for statistical improvement in communication, gross motor, fine motor, problem-solving, and personal-social, as taught by Kong with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to evaluate ASD type symptoms as disclosed in Amat’s method, with a common, widely available assessment such as ASQ-3 taught by Kong.
Regarding claim 11, Amat teaches mental health problems were evaluated in the subgroup of participants older than 6 years of age, specifically, BPL1 induced modest but significant improvements (decrease in test score) in withdrawn/depression symptoms, and a trend toward improvement in attention problems compared to placebo, the rest of the symptom dimensions evaluated did not reach statistical significance, although several showed numerical decreases (pg. 9, sec. 3.5, Table 4).
Amat does not teach abnormal behavioral characteristics are measured by Third Edition GARS-3 score (GARS-3) for one or more of RRB, SI, SC, ER, CS and MS.
However, Kong teaches abnormal behavioral characteristics are measured by Third Edition GARS-3 score (GARS-3) for one or more of RRB, SI, SC, ER, CS and MS, wherein patients aged 36 months or older, received the GARS-3 from the PWS Care & Support Center (pg. 2, col. 2, para 6). Kong discloses GARS-3 is a norm-referenced screening instrument used to identify persons with autism spectrum disorders for age 3-22, wherein the items are grouped into six subscales: restrictive, repetitive behaviors (RB), social interaction (SI), social communication (SC), emotional responses (ER), cognitive style (CS), and maladaptive speech (MS) (pg. 3, col. 1, para 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of treating PWS with a probiotic, as taught by Amat, by an evaluation of the patient’s progress of decreasing abnormal behavioral characteristics as measured by Third Edition GARS-3 score (GARS-3) for one or more of RRB, SI, SC, ER, CS and MS as taught by Kong with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to evaluate ASD type symptoms as disclosed in Amat’s method, with a screening instrument that has a proven high rate of validity and reliability that is used to identify persons with ASD as taught by Kong (pg. 3, col. 1, para 1).
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Amat.
Amat teaches probiotic compositions administered in a method of treating PWS comprising B. lactis BL-11 (title), and teach inclusion criteria were genetically confirmed PWS diagnosis, age between 2 to 19 years, and being on a stable diet and medication regimen for at least two months before enrollment, with special attention to growth hormone (GH) therapy and metformin use (pg. 3, sec. 2.2).
Amat does not teach a composition comprising the probiotic and a growth hormone, however it would be prima facie obvious to one of ordinary skill in the art to combine a probiotic with a growth hormone in a composition for the treatment of PWS, since growth hormone therapy is a known treatment for PWS, as taught by Amat.
Claims 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Amat as applied to claim 22 above, and further in view of Minami.
Amat teaches methods of administering a probiotic comprising B. lactis in combination with human growth hormone therapy, and demonstrated a significant decrease in abdominal fat mass after BPL1 supplementation compared to placebo group on subjects older than 4.5 years (pg. 7, sec. 3.3).
Amat does not teach a composition wherein the probiotic comprises Lactobacillus reuteri in combination with human growth hormone therapy.
However, Minami teaches a method and composition that are effective in obesity treatment using probiotics such as bifidobacteria and lactobacilli (abstract). Minami teaches body-mass index (BMI) as the measurement for obesity, wherein the "obesity preliminary group" refers to mild obesity having an BMI value of 25 or greater and less than 30, and "obesity" refers to obesity having an BMI value of 30 or greater, which meets the limitation in claim 8 (pg. 15, para 1). Minami teaches the probiotic dose can be divided from once a day to multiple times per day at a dose of 1 x 103 CFU to 1 x 1012 CFU, which meets the limitations of 3 x 103 CFU and twice per day in claim 17 (pg. 7, para 2-4). Minami teaches the probiotic can comprise B. animalis subsp. lactis and L. reuteri, but is not particularly limiting to the species (pg. 11, para 11, pg. 12, para 1).
Therefore, it would have been prima facie obvious to formulate a composition comprising a combination of a probiotic B. lactis and human growth hormone that is effective at decreasing abdominal fat mass as taught by Amat, and combine with the probiotic L. reuteri which is effective in obesity treatment, as taught by Minami.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 5-9, and 12-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-7, 9, 13-19, and 21 of copending Application No. 18/267969. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims anticipate the instant claims.
Regarding instant claims 1-2, ‘969 recites a method of treating PWS to a pediatric subject by administering an effective amount of a probiotic comprising B. lactis BL-11 strain or the probiotic further comprises a Saccharomyces sp., an additional Bifidobacterium sp., a Bacillus sp., and/or Eubacterium halli, wherein the treatment comprises administering the effective amount for at least about 3 weeks, wherein the subject is suffering from short stature, and the subject’s height after treatment is increased compared to before treatment. The instant claims recite a broader method of treating PWS, which ‘pediatric subject’ and ‘BL-11 strain’, are in essence ‘species’ of the generic invention recited in claims 1-2 of the instant application, thus anticipating the instant claims.
Regarding instant claim 5, claims 1 and 5 of ‘969 recites the subject is suffering from short stature, and the subject’s height after treatment is increased compared to before treatment, and wherein the subject is further suffering from one or more of the following symptoms or conditions: obesity, social deficits, fine motor abnormalities, developmental delay, and abnormal behavioral characteristics; wherein after treatment, the subject's symptoms or conditions are improved as compared to before treatment, thus anticipating the claim.
Regarding instant claim 6, claim 6 of ‘969 recite wherein the developmental delay comprises one or more of communication, gross motor control, fine motor control, problem-solving, and personal- social interaction, thus anticipating the claim.
Regarding instant claim 7, claim 7 of ‘969 recites wherein the abnormal behavioral characteristics comprise one or more of restrictive, repetitive behaviors (RRB), aberrant social interaction (SI), aberrant social communication (SC), aberrant emotional responses (ER), aberrant cognitive style (CS), and maladaptive speech (MS), thus anticipating the claim.
Regarding instant claim 8, claim 1 of ‘969 recites a method of treating with B. lactis BL-11 by administering to a subject is suffering from short stature, and the subject’s height after treatment is increased compared to before treatment, thus anticipating the claim.
Regarding instant claims 9 and 12, claim 9 of ‘969 recites “wherein the subject exhibits improved psychopathology severity after treatment, as measured by Clinical Global Impression- Improvement (CGI-I) and/or Clinical Global Impression-Severity (CGI-S)” when treated with B. lactis, thus anticipating the claims.
Regarding instant claim 13, claim 13 of ‘969 recites “The method of claim 1, wherein the treatment comprises administering an effective dose of the probiotic once per day, twice per day, three times per day, or four times per day.”, thus anticipating the claim.
Regarding instant claim 14, claim 14 of ‘969 recites “The method of claim 1, wherein the treatment comprises administering an effective dose of the probiotic for at least about 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or at least about 12 weeks.”, thus anticipating the claim.
Regarding instant claim 15, claim 15 of ‘969 recites “The method of claim 1, wherein the effective amount comprises about 1x105 to about 1x1015, about 1x106 to about 1x1014, about 1x107 to about 1x1 about 1x108 to about 1x1012, about 1x109 to about 1x1011, about 1x1010 to about 9x1010, or about 3x1010 colony forming units (CFU) of probiotic.”, thus anticipating the claim.
Regarding instant claim 16, claim 16 of ‘969 recites “wherein the subject is administered one or more additional therapeutics” thus anticipating the claim.
Regarding instant claim 17, claim 17 of ‘969 recites “wherein the probiotic is administered twice per day at a dose of about 3x1010 CFU for 12 weeks, and wherein after treatment, the subject exhibits a statistically relevant improvement in one or more of BMI, fine motor function, and problem solving skills as measured by ASQ-3 testing.”, thus anticipating the claim.
Regarding instant claim 18, claim 18 of ‘969 recites “wherein the subject's microbiome composition is different after the treatment as compared to before the treatment.”, thus anticipating the claim.
Regarding instant claims 19-20, claim 19 recites “wherein the microbiome difference comprises a decrease in one or more of Comamonadaceae, Escherichia-Shigella, Porphyromonas, and Ruminococcus torques, and/or wherein the microbiome difference comprises an increase in one or more of Bifidobacterium, Lactobacillus, Faecalibacteria, Roseburia, and Alistipes.”, thus anticipating the claim.
Regarding claim 21, claim 21 of ‘969 recite “wherein the microbiome difference comprises a decrease in Rothia.”, which anticipates the claim.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-9 and 12-21 are rejected on the ground of nonstatutory double patenting as being unpatentable claims 1 and 16 of copending Application No. 18/267969 in view of Minami.
As described above, instant claim 1-2, 5-9, and 12-21 are anticipated by claims 1-2, 5-7, 9, 13-19, and 21 of the copending application ‘969.
Regarding instant claims 3-5, ‘969 claims do not recite B. lactis as a treatment for obesity in patient with PWS, but does not recite the probiotic comprises L. reuteri and B. lactis as a treatment for obesity symptom of PWS.
However, Minami teaches a method and composition that are effective in obesity treatment using probiotics such as bifidobacteria and lactobacilli (abstract). Minami teaches the probiotic can comprise B. animalis subsp. lactis and L. reuteri, but is not particularly limiting to the species (pg. 11, para 11, pg. 12, para 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to utilize the method recited in ‘969 to treat PWS with B. lactis, and add an additional L. reuteri species to the probiotic, as both species are effective at treating obesity as taught by Minami.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2 and 5-21 are rejected on the ground of nonstatutory double patenting as being unpatentable claims 1-2, 5-7, 9, 13-19, and 21 of copending Application No. 18/267969 in view of Kong.
As described above, instant claim 1-2, 5-9, and 12-21 are anticipated by claims 1-2, 5-7, 9, 13-19, and 21 of the copending application ‘969.
Regarding instant claim 10, claims 5-6 of ‘969 recites the pediatric subject is suffering from developmental delays and abnormal behavioral characteristics, but does not recite the ASQ-3 score is statistically improved after probiotic treatment.
However, Kong teaches early screening and risk factors of Autism Spectrum Disorder (ASD) in a large cohort of Chinese patients with PWS (title). Kong teaches developmental delays are measured by Ages and Stages Questionnaires, 3rd Edition (ASQ-3) score for one or more of communication, gross motor function, fine motor function, problem-solving, and personal-social interaction (pg. 2, col. 2, para 5). The ASQ-3 was handed or mailed to the parents of the 103 participants younger than 36 months old, and is one of the most widely available development, communication, and behavior screening tools for young children (pg. 2, col. 2, para 5). The ASQ-3 provides parents with information about the developmental status of their young child across five developmental domains: communication, gross motor, fine motor, problem-solving, and personal-social (pg. 2, col. 2, para 5).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of treating PWS with a probiotic, as recited by ‘969, by adding an evaluation of the patient’s progress of developmental delays with the ASQ-3 assessment for statistical improvement in communication, gross motor, fine motor, problem-solving, and personal-social, as taught by Kong with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to evaluate ASD type symptoms as recited in ‘969 method, with a common, widely available assessment such as ASQ-3 taught by Kong.
Regarding instant claim 11, claims 5-6 of ‘969 recites the pediatric subject is suffering from developmental delays and abnormal behavioral characteristics, but does not recite the GARS-3 score is statistically improved after probiotic treatment.
However, Kong teaches abnormal behavioral characteristics are measured by Third Edition GARS-3 score (GARS-3) for one or more of RRB, SI, SC, ER, CS and MS, wherein patients aged 36 months or older, received the GARS-3 from the PWS Care & Support Center (pg. 2, col. 2, para 6). Kong discloses GARS-3 is a norm-referenced screening instrument used to identify persons with autism spectrum disorders for age 3-22, wherein the items are grouped into six subscales: restrictive, repetitive behaviors (RB), social interaction (SI), social communication (SC), emotional responses (ER), cognitive style (CS), and maladaptive speech (MS) (pg. 3, col. 1, para 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of treating PWS with a probiotic, as recited by ‘969, by an evaluation of the patient’s progress of decreasing abnormal behavioral characteristics as measured by Third Edition GARS-3 score (GARS-3) for one or more of RRB, SI, SC, ER, CS and MS as taught by Kong with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to evaluate ASD type symptoms as recited in ‘969 method, with a screening instrument that has a proven high rate of validity and reliability that is used to identify persons with ASD as taught by Kong (pg. 3, col. 1, para 1).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 5-9, and 12-22 are rejected on the ground of nonstatutory double patenting as being unpatentable claims 1-2, 5-7, 9, 13-19, and 21 of copending Application No. 18/267969 in view of Amat.
As described above, instant claim 1-2, 5-9, and 12-21 are anticipated by claims 1-2, 5-7, 9, 13-19, and 21 of the copending application ‘969.
Regarding instant claim 22, the claims of ‘969 recite a composition comprising one or more probiotics, but do not recite a composition comprising one or more probiotics and a growth hormone.
However, Amat teaches probiotic compositions administered in a method of treating PWS comprising B. lactis BL-11 (title), and teach inclusion criteria were genetically confirmed PWS diagnosis, age between 2 to 19 years, and being on a stable diet and medication regimen for at least two months before enrollment, with special attention to growth hormone (GH) therapy and metformin use (pg. 3, sec. 2.2).
Amat does not teach a composition comprising the probiotic and a growth hormone, however it would be prima facie obvious to one of ordinary skill in the art to combine a probiotic with a growth hormone in a composition for the treatment of PWS, since growth hormone therapy is a known treatment for PWS, as taught by Amat. Therefore, it would have been prima facie obvious to formulate the composition recited in instant claim 22 comprising one or more probiotics and a growth hormone, as taught by Amat.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 5-9, and 12-24 are rejected on the ground of nonstatutory double patenting as being unpatentable claims 1-2, 5-7, 9, 13-19, and 21 of copending Application No. 18/267969 in view of Amat and Minami.
As described above, instant claims 1-2, 5-9, and 12-22 are obvious over claims 1-2, 5-7, 9, 13-19, and 21 of the copending application ‘969 in view of Amat.
Regarding instant claims 23-24, claims 1 and 16 of ‘969 recite a method for treating PWS by administering a probiotic and one or more additional therapeutics, but do not recite a composition comprising a probiotic (L. reuteri) and human growth hormone.
However, Amat teaches probiotic compositions administered in a method of treating PWS comprising B. lactis BL-11 (title), and teach inclusion criteria were genetically confirmed PWS diagnosis, age between 2 to 19 years, and being on a stable diet and medication regimen for at least two months before enrollment, with special attention to growth hormone (GH) therapy and metformin use (pg. 3, sec. 2.2). Amat does not explicitly teach a composition comprising the probiotic and a growth hormone, however it would be prima facie obvious to one of ordinary skill in the art to combine a probiotic with a growth hormone in a composition for the treatment of PWS, since growth hormone therapy is a common and routine treatment for PWS, thus would be obvious to combine into a composition. Amat teaches when administering a probiotic comprising B. lactis in combination with human growth hormone therapy demonstrated a significant decrease in abdominal fat mass after BPL1 supplementation compared to placebo group on subjects older than 4.5 years (pg. 7, sec. 3.3). Amat does not teach a composition wherein the probiotic comprises Lactobacillus reuteri in combination with human growth hormone therapy.
Minami teaches a method and composition that are effective in obesity treatment using probiotics such as bifidobacteria and lactobacilli (abstract). Minami teaches body-mass index (BMI) as the measurement for obesity, wherein the "obesity preliminary group" refers to mild obesity having an BMI value of 25 or greater and less than 30, and "obesity" refers to obesity having an BMI value of 30 or greater, which meets the limitation in claim 8 (pg. 15, para 1). Minami teaches the probiotic dose can be divided from once a day to multiple times per day at a dose of 1 x 103 CFU to 1 x 1012 CFU, which meets the limitations of 3 x 103 CFU and twice per day in claim 17 (pg. 7, para 2-4). Minami teaches the probiotic can comprise B. animalis subsp. lactis and L. reuteri, but is not particularly limiting to the species (pg. 11, para 11, pg. 12, para 1).
Therefore, it would have been prima facie obvious to formulate a composition comprising a combination of a probiotic B. lactis and additional therapeutic in the treatment of PWS as recited in ‘969, and formulate a composition comprising B. lactis with human growth hormone that is effective at decreasing abdominal fat mass as taught by Amat, and substitute with the probiotic L. reuteri which is effective in obesity treatment as taught by Minami with a reasonable expectation of success. Thus, the method of administering the claimed composition recited in ‘969 and taught by Amat and Minami, would have been an obvious use of the same composition.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 14, and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 7 of copending Application No. 18/703879 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the copending claims.
Regarding instant claims 1-2, claims 1-4 of ‘879 recite a method to alter salivary microbiota by orally administering B. animalis subsp. lactis (B. lactis) to a subject diagnosed with PWS, which are all in essence ‘species’ of a method for treating PWS comprising administering an effective amount of a probiotic, wherein the probiotic comprises Bifidobacterium sp., thus anticipates the claims.
Regarding instant claim 14, claim 5 of ‘879 recites the probiotic is administered for 12 weeks or more, which anticipates the claim.
Regarding instant claim 18, claim 7 of ‘879 recites the salivary microbiota comprises the presence or increase of one or more genera selected from, Bifidobacterium, which ‘salivary microbiota’ is in essence a ‘species’ of microbiome of the subject, which anticipates claim 18.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 5-8, 10-11, and 13-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-8, 10-11, 13-20 of copending Application No. 18/972671. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the copending claims.
Regarding instant claims 1-2, ‘671 recites a method of treating PWS by administering an effective amount of a probiotic comprising L. reuteri LR-99 strain or the probiotic further comprises a Saccharomyces sp., an additional Lactobacillus sp.,a Bacillus sp., and/or Eubacterium halli, wherein the treatment comprises administering the effective amount for at least about 3 weeks, wherein the subject is suffering from short stature, and the subject’s height after treatment is increased compared to before treatment. The instant claims recite a broader method of treating PWS, which ‘pediatric subject’ and ‘LR-99 strain’, are in essence ‘species’ of the generic invention recited in claims 1-2 of the instant application, thus anticipating the instant claims.
Regarding instant claim 5, claims 1 and 5 of ‘671 recites the subject is suffering from short stature, and the subject’s height after treatment is increased compared to before treatment, and wherein the subject is further suffering from one or more of the following symptoms or conditions: obesity, social deficits, fine motor abnormalities, developmental delay, and abnormal behavioral characteristics; wherein after treatment, the subject's symptoms or conditions are improved as compared to before treatment, thus anticipating the claim.
Regarding instant claim 6, claim 6 of ‘671 recite wherein the developmental delay comprises one or more of communication, gross motor control, fine motor control, problem-solving, and personal- social interaction, thus anticipating the claim.
Regarding instant claim 7, claim 7 of ‘671 recites wherein the abnormal behavioral characteristics comprise one or more of restrictive, repetitive behaviors (RRB), aberrant social interaction (SI), aberrant social communication (SC), aberrant emotional responses (ER), aberrant cognitive style (CS), and maladaptive speech (MS), thus anticipating the claim.
Regarding instant claim 8, claim 8 of ‘671 recites a method of treating with LR-99 by administering to a subject is suffering from obesity, and the subject’s BMI after treatment is lower compared to before treatment, thus anticipating the claim.
Regarding instant claims 10-11, claims 10-11 of ‘671 recite the ASQ-3 and GARS-3 scores are statistically improved after treatment, thus anticipating the claims.
Regarding instant claim 13, claim 13 of ‘671 recites “The method of claim 1, wherein the treatment comprises administering an effective dose of the probiotic once per day, twice per day, three times per day, or four times per day.”, thus anticipating the claim.
Regarding instant claim 14, claim 14 of ‘671 recites “The method of claim 1, wherein the treatment comprises administering an effective dose of the probiotic for at least about 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or at least about 12 weeks.”, thus anticipating the claim.
Regarding instant claim 15, claim 15 of ‘671 recites “The method of claim 1, wherein the effective amount comprises about 1x105 to about 1x1015, about 1x106 to about 1x1014, about 1x107 to about 1x1 about 1x108 to about 1x1012, about 1x109 to about 1x1011, about 1x1010 to about 9x1010, or about 3x1010 colony forming units (CFU) of probiotic.”, thus anticipating the claim.
Regarding instant claim 16, claim 16 of ‘671 recites “wherein the subject is administered one or more additional therapeutics” thus anticipating the claim.
Regarding instant claim 17, claim 17 of ‘671 recites “wherein the probiotic is administered twice per day at a dose of about 3x1010 CFU for 12 weeks, and wherein after treatment, the subject exhibits a statistically relevant improvement in one or more of BMI, fine motor function, and problem solving skills as measured by ASQ-3 testing.”, thus anticipating the claim.
Regarding instant claim 18, claim 18 of ‘671 recites “wherein the subject's microbiome composition is different after the treatment as compared to before the treatment.”, thus anticipating the claim.
Regarding instant claims 19-20, claims 19-20 of ‘671 recites “wherein the microbiome difference comprises a decrease in one or more of Comamonadaceae, Escherichia-Shigella, Porphyromonas, and Ruminococcus torques, and/or wherein the microbiome difference comprises an increase in one or more of Bifidobacterium, Lactobacillus, Faecalibacteria, Roseburia, and Alistipes.”, thus anticipating the claim.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-8, 10-11, 13-20, and 22-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-8, 10-11, 13-20 of copending Application No. 18/972671 in view of Amat.
As described above, claims 1-2, 5-8, 10-11, and 13-20 are anticipated by claims 1-2, 5-8, 10-11, 13-20 of copending Application No. 18/972671.
Regarding instant claims 3-4, ‘671 does not recite the probiotic used to treat PWS also comprises B. lactis.
However, Amat teaches effects of Bifidobacterium animalis subsp. lactis BPL1 supplementation in children and adolescents with Prader-Willi Syndrome (PWS) (title). Amat teaches daily administration of BLP1 to participants for a 12-week period, wherein 100mg of BPL1 contained 1010 CFUs (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to modify the method of treating PWS recited in ‘671 and include B. lactis in the probiotic composition, as this is an effective treatment for PWS as taught by Amat.
Regarding instant claims 22-24, the claims of ‘671 recite a composition comprising LR-99, but do not recite a composition comprising LR-99 and a human growth hormone.
However, Amat teaches probiotic compositions administered in a method of treating PWS comprising B. lactis BL-11 (title), and teach inclusion criteria were genetically confirmed PWS diagnosis, age between 2 to 19 years, and being on a stable diet and medication regimen for at least two months before enrollment, with special attention to growth hormone (GH) therapy and metformin use (pg. 3, sec. 2.2). Amat does not explicitly teach a composition comprising the probiotic and a growth hormone, however it would be prima facie obvious to one of ordinary skill in the art to combine a probiotic with a growth hormone in a composition for the treatment of PWS, since growth hormone therapy is a common and routine treatment for PWS, thus would be obvious to combine into a composition. Amat teaches when administering a probiotic comprising B. lactis in combination with human growth hormone therapy demonstrated a significant decrease in abdominal fat mass after BPL1 supplementation compared to placebo group on subjects older than 4.5 years (pg. 7, sec. 3.3).
Therefore, it would have been prima facie obvious to formulate a composition comprising a combination of a probiotic L. reuteri and additional therapeutic in the treatment of PWS as recited in ‘671, and formulate a composition comprising L. reuteri with human growth hormone as taught by Amat, with a reasonable expectation of success. Thus, the method of administering the claimed composition recited in ‘671 and taught by Amat, would have been an obvious use of the same composition.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2 and 5-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-8, 10-11, 13-20 of copending Application No. 18/972671 in view of Dangles.
As described above, claims 1-2, 5-8, 10-11, and 13-20 are anticipated by claims 1-2, 5-8, 10-11, 13-20 of copending Application No. 18/972671.
Regarding instant claims 9 and 12, claim 5 of ‘671 recites the subject is suffering from abnormal behavioral characteristics, wherein the subject’s condition is improved after treatment, but does not recite the subject is suffering from varying severities of psychopathology is measured by CGI-I.
However, Dangles teaches methods of treating PWS, and evaluating varying severities of psychopathology as measured by Clinical Global Impression-Improvement (CGl-I) which meets the limitation of claim 9 (abstract, para 115). CGI rating scales are commonly used measures of symptom severity, treatment response and the efficacy of treatments in treatment studies of subjects with psychiatric, neurological or behavioral disorders (para 115). Dangles teaches the CGI scale is a 7-point clinician rating of illness severity (CGI-S; 1=normal, not at all ill, 7=among the most extremely ill patients), at the beginning of the trial and a 7-point clinician rating of improvement of patient condition, during and at the end of the trial (CGI- I; 1=very much improved since baseline, 7=very much worse from baseline), wherein the CGI-S scale was completed during Visit 1, and the CGl-I scale was completed during Visit 4 and on Day 8 of the trial (para. 116). Dangles teaches at Day 8 and Day 15, the CGI scores were statistically improved in the treatment method (pg. 9, Table 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of treating PWS with a probiotic comprising LR-99 recited in ‘671 and add an evaluation of subjects suffering from varying severities of psychopathology measured by CGI-I before and after treatment, as taught by Dangles. One of ordinary skill in the art would have been motivated to include this assessment of improved mental health, as this is a common assessment used in methods for treating PWS as disclosed in Dangles. Furthermore, it would have been obvious to modify the ‘671 method of assessing PWS treatment by using CGI-I taught by Dangles for the purpose of observing changes in PWS subjects.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA EDWARDS whose telephone number is (571)270-0938. The examiner can normally be reached M-F 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, Louise Humphrey can be reached at (571) 272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/JESSICA EDWARDS/
Examiner, Art Unit 1657
Prosecution Insights