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 .
Claims 1-31 are under examination on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-31 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. In claim 1 (and its dependent claims 2-15) and claim 16 (and its dependent claims 17-31) the term “derived” is ambiguous. Siad term has not been explicitly defined in the disclosure. Therefore, it is unknown if applicant is referring to “isolated” or “modified” fecal microbiota in base claims 1 and 16 or whether he/she is referring to a microbiota that is modified/mutated relative to the microbiota from a healthy subject. Appropriate clarification is required.
Claims 2-15 and 17-31 are merely rejected for depending from claims 1 and 16 respectively.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 3-15, 25-31 /are rejected under 35 U.S.C. 103 as being obvious over Mazmanian et al., “Mazmanian” (US 2024/0000862, 1/2024 (see also its corresponding US patent No. 12,329,786). From now on said patent publication will be used to cite relevant text in this rejection.
The applied reference has a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Mazmanian in claim 2-18 recites:
“2. A method of reducing neuroinflammation in a subject having a disease, the method comprising: administering a composition comprising an inhibitor of a short chain fatty acid (SCFA) comprising propionate or butyrate; and increasing a level of a Parkinson's disease (PD)-protective bacteria in a gut microbiota of the subject; or decreasing a level of a PD-enhancing bacteria in a gut microbiota of the subject, wherein increasing the level of the PD-protective bacteria or decreasing the level of the PD-enhancing bacteria reduces neuroinflammation in the subject.
3. The method of claim 2, wherein the disease is a neurodegenerative disease.
4. The method of claim 2, wherein the disease is PD, dementia with Lewy body disease, or multiple system atrophy.
5. The method of claim 2, wherein the PD-protective bacteria is Lachnospiraceae, Rikenellaceae, Peptostreptococcaceae, or Butyricicoccus
6. The method of claim 2, wherein the PD-enhancing bacteria belongs to Proteus sp., Bilophila sp., Roseburia sp., Pseudoramibacter Eubacterium, or Veillonellaceae family.
7. The method of claim 2, wherein the PD-enhancing bacteria belongs to KEGG family K00929, K01034, or K01035.
8. The method of claim 2, wherein increasing the level of the PD-protective bacteria in the gut microbiota of the subject comprises introducing gut microbiota from a healthy subject to the subject.
9. The method of claim 8, wherein introducing gut microbiota from a healthy subject comprises fecal transplantation, microbiota conventionalization, microbial colonization, reconstitution of gut microbiota, probiotic treatment, or a combination thereof.
10. The method of claim 2, further comprising administering one or more antibiotics to the subject.
11. The method of claim 10, wherein the one or more antibiotics comprise ampicillin, vancomycin, neomycin, gentamycin, erythromycin, or any combination thereof.
12. The method of claim 2, wherein reducing neuroinflammation comprises reducing TNF-α production, reducing interleukin-6 (IL-6), or reducing αSyn aggregation.
13. The method of claim 2, wherein reducing neuroinflammation comprises reducing microglia activation in the subject.
14. The method of claim 2, further comprising identifying the subject as having a disease when the subject has an abnormal level of aggregation of α-synuclein (αSyn).
15. The method of claim 14, further comprising measuring a rate and/or level of αSyn aggregation in the brain of the subject, the clearance rate and/or level of insoluble αSyn protein aggregate in the brain of the subject, or a combination thereof.
16. The method of claim 2, wherein the composition further comprises a pharmaceutically acceptable carrier.
17. The method of claim 2, wherein the composition is formulated for oral administration.
18. The method of claim 2, wherein the method further comprises: administering a composition comprising an inhibitor of a short chain fatty acid (SCFA) comprising propionate or butyrate; increasing a level of a Parkinson's disease (PD)-protective bacteria in a gut microbiota of the subject; and decreasing a level of a PD-enhancing bacteria in a gut microbiota of the subject, wherein increasing the level of the PD-protective bacteria and decreasing the level of the PD-enhancing bacteria reduces neuroinflammation in the subject.”
In [0017], Mazmanian recites:
“In some embodiments, the parkinsonian symptom comprises tremor, bradykinesia, muscle rigidity, impaired posture and balance, loss of automatic movements, speech impairment, writing impairment, or any combination thereof.”
In [0052], according to Mazmanian
“methods for delaying or reducing the likelihood of onset of a neurodegenerative disorder, methods for improving a motor deficit in a subject in need (e.g., a patient having a neurodegenerative disorder). The methods, in some embodiments, comprise adjusting the composition of gut microbiota in the subject. The methods, in some embodiments, further improve one or more physical impairments in the subject. The methods can, for example, improves one or more GI functions of the subject, relieves constipation of the subject. Non-limiting examples of the motor deficits include tremors, muscle rigidity, bradykinesia, impaired gait, and any combination thereof. In some embodiments, the neurodegenerative disease is a synucleinopathy which includes but not limited to a primary or idiopathic parkinsonism, secondary or acquired parkinsonism, hereditary parkinsonism, Parkinson plus syndromes or multiple system degeneration, and any combination thereof.
In [0110] of said publication, reference is made to fecal transplantation in mice, wherein said transplantation is intragastric.
Therefore, it is believed that the teachings of Mazmanian as a whole render his invention obvious.
Claim 2, 16-24 are rejected under 35 U.S.C. 103 as being obvious over Mazmanian (cited above) in view of Parker et al., “parker (Microbiome (2022) 10:68, https://doi.org/10.1186/s40168-022-01243-w).
The applied reference has a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
As mentioned above, Mazmanian tecahes and claims a method of reducing neuroinflammation in a subject having a disease, the method comprising: administering a composition comprising an inhibitor of a short chain fatty acid (SCFA) comprising propionate or butyrate; and increasing a level of a Parkinson's disease (PD)-protective bacteria in a gut microbiota of the subject; or decreasing a level of a PD-enhancing bacteria in a gut microbiota of the subject, wherein increasing the level of the PD-protective bacteria or decreasing the level of the PD-enhancing bacteria reduces neuroinflammation in the subject,
wherein increasing the level of the PD-protective bacteria in the gut microbiota of the subject comprises introducing gut microbiota from a healthy subject to the diseased subject.
Said publication does mention assessing the age of the diseased subject and administering to the subject fecal microbiota from a healthy subject who is at least 10 years younger than the diseased subject.
Parker in its abstract, teaches that microbiota composition profiles and key species enriched in young or aged mice are successfully transferred by FMT (fecal microbiota) between young and aged mice and that FMT modulates resulting metabolic pathway profiles.
According to Parker, the transfer of aged donor microbiota into young mice accelerates age-associated central nervous system (CNS) inflammation, retinal inflammation, and cytokine signaling and promotes loss of key functional protein in the eye, effects which are coincident with increased intestinal barrier permeability. Conversely, these detrimental effects can be reversed by the transfer of young donor microbiota. These findings demonstrate that the aging gut microbiota drives detrimental changes in the gut–brain and gut–retina axes suggesting that microbial modulation may be of therapeutic benefit in preventing inflammation related tissue decline in later life (see also conclusions section).
In page 3, column 1, according to Parker, In the brain microglial cells play multiple roles in regulating inflammatory responses and neural functioning and are now considered central to the pathology of neurodegenerative diseases. Studies using germ-free mice, antibiotic treatment, and selective microbial colonization suggest that the intestinal microbiota can regulate microglial maturation and function in the enteric and central nervous systems Attenuation of pathology following microbial modulation, in transgenic mouse models of Alzheimer’s disease], also supports a role for the microbiota in inflammaging in the brain.
Before the effective filing of this application, it would have been obvious to one of ordinary skill in the art to start with the method of Mazmanian and assess the age of the diseased subject having neurodegenerative disorder and transplant the FMT of Parker from a younger heathy subject into said diseased subject, wherein the diseased subject was optionally treated with antibiotics prior to transplantation. This is because, Parker (see page 19, column 2) teaches that loss of intestinal barrier integrity and elevated circulating pro-inflammatory cytokine concentrations are linked with the polarization of CNS microglia toward a pro-inflammatory phenotype and promote neurodegenerative disease.
One of ordinary skill in the art is motivated in substituting the FMT of the disease subject with that a younger obviously healthy subject in the method of Mazmanian because Parker teaches that such FMT transplantation may improve some symptoms of neurodegenerative disease (including gut function, motor neuron deficit symptoms, alpha-synuclein aggregation inhibition etc. in said subject. Obviously, the younger the subject the better outcome of such transplantation (see for example, the comparison of the gut microbiome of a 20-year-old versus a 50-year-old, based on a key word search on 9/19/26 in common databases online, attached).
Finally, one of ordinary skill in the art has a reasonable expectation of success in transplanting the fecal microbiota of a young healthy subject into the gut system of the diseased subject who/which is at least 10 or 20 years older if the subject is human) because such procedures were fully established in the prior art, before the effective filing of this application.
It should be noted that the attachment mentioned above, is not a part of this 103 rejection and is merely provided to show the level of knowledge of one of ordinary skill, prior to the filing of this application.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARYAM MONSHIPOURI whose telephone number is (571)272-0932. The examiner can normally be reached full-flex.
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/MARYAM MONSHIPOURI/Primary Examiner, Art Unit 1651
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