DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/19/2026 has been entered.
Election/Restrictions
Applicant’s election without traverse of Species A (i.e., Single and specific composition indicating the following: 1. Single and specific bacterial species, Applicant’s Election: Prevotella histicola; 2. Whether the Prevotella is live or killed, Applicant’s Election: live); and Species B (i.e., Single and specific lung condition to be treated indicating the following: 1. Whether the lung condition is caused by infection, Applicant’s Election: emphysema; and if so, a single and specific cause of infection, e.g., viral infection; a. Single and specific infection if the lung condition is caused by infection, e.g., viral pneumonia), in the reply filed on July 8th 2024, are acknowledged.
Please note that Species A has been expanded to include Prevotella melaninogenica; and Species B has been expanded to include COPD.
Claims 3, 18-24, 27-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 8th 2024.
Priority
The present application claims status as a 371 (National Stage) of PCT/US2020/038084 filed June 17th 2020, and claims the benefit under 35 U.S.C 119 (e) to U.S. Provisional Application No. 62/862,186 filed June 17th 2019.
Status of Claims
Claims 1-30 were originally filed and amended on December 14th 2021. The amendment amended claims 4-7, 21-22, 27-28; and cancelled claims 8-17.
The amendment filed on July 8th 2024, amended claims 1 and 28.
The amendment filed on February 12th 2025, cancelled claims 18-30, and amended claims 1, 4-5 and 7.
The amendment filed on April 14th 2025, amended claim 1.
The amendment filed on September 24th 2025, amended claims 1 and 6, and added new claim 31.
The amendment filed on March 19th 2026, canceled claim 31, and amended claim 1.
Claims 1-7 are currently pending and under consideration.
Claim Interpretation
For purposes of applying prior art, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation set forth below, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
For claim 1, regarding the scope of “treating,” it is noted that the instant specification does not define what constitutes the term “treating.” Pursuant to MPEP 2111.01, under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the time of the invention. In the instant case The Britannica Dictionary defines “treating” as to deal with (a disease, infection, etc.) in order to make someone feel better or become healthy again (See Britannica Dictionary, “treat”, 2022. Pp. 1-2 at pg. 2, retrieved from https://www.britannica.com/dictionary/treat on 08/07/2024). As such, the Examiner is interpreting treating as dealing with a disease in order to make someone feel better or become healthy again, but excluding preventing the disease from occurring.
Regarding the scope of “emphysema,” it is noted that the instant specification does not define what constitutes the term “emphysema.” Pursuant to MPEP 2111.01, under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the time of the invention. In the instant case Medline Plus teaches that emphysema is a type of COPD (chronic obstructive pulmonary disease) (See Medline Plus, Emphysema. 2016, pp. 1-7 at pg. 1, retrieved from https://medlineplus.gov/emphysema.html on 08/02/2024). COPD is a group of lung diseases that make it hard to breathe and get worse over time (See Medline Plus, pg. 1, paragraph 1). Emphysema affects the air sacs in the lungs (See Medline Plus, pg. 1, paragraph 1). In emphysema, the walls between many of the air sacs in the lungs are damaged (See Medline Plus, pg. 1, paragraph 3). This causes the air sacs to lose their shape and become floppy (See Medline Plus, pg. 1, paragraph 3). The damage also can destroy the walls of the air sacs, leading to fewer and larger air sacs instead of many tiny ones (See Medline Plus, pg. 1, paragraph 3). This makes it harder for the lungs to move oxygen in and carbon dioxide out of the body (See Medline Plus, pg. 1, paragraph 3). Therefore, the Examiner is interpreting Emphysema as a chronic obstructive pulmonary disease where the air sacs in the lungs lose their shape and become floppy making it harder for the lungs to move oxygen in and carbon dioxide out of the body.
Response to Arguments
1. Applicant’s arguments, see Remarks, filed 03/19/2026, with respect to the 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 (i.e., new matter); have been fully considered and are persuasive. The 35 U.S.C. 112(a) rejection to claims 1-7 and has been withdrawn.
2. Applicant’s arguments, see Response, filed on 03/19/2026, with respect to 35 U.S.C. 103
as being unpatentable over WO2019/051381A1 published on March 14th 2019, cited in the IDS filed on 05/09/2022 (herein after “Evelo”), in view of Lappalainen et al., Am J Respir Cell Mol Biol. 2005, vol. 32, pp. 311-318 (herein after “Lappalainen”), Lee et al., Nature Medicine, 2007 v. 13, pp. 567-569 (herein after “Lee”), US 8,617,536 B2 Date of Patent: Dec. 31, 2013, cited in the IDS filed on 05/09/2022 (herein after “ Murray et al.”), and Papandrinopoulou et al., Pulmonary Medicine. 2012, vol. 2012, article ID 542769, pp. 1-6 (herein after “Papandrinopoulou”); have been fully considered but are not persuasive. The 35 U.S.C. 103 rejection to claims 1-7 has been maintained.
Maintained/Modified Rejection in Light of Amendments
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.
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness
(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
1. Claims 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over WO2019/051381A1 published on March 14th 2019, cited in the IDS filed on 05/09/2022 (herein after “Evelo”), in view of Lappalainen et al., Am J Respir Cell Mol Biol. 2005, vol. 32, pp. 311-318 (herein after “Lappalainen”), Lee et al., Nature Medicine, 2007 v. 13, pp. 567-569 (herein after “Lee”), US 8,617,536 B2 Date of Patent: Dec. 31, 2013, cited in the IDS filed on 05/09/2022 (herein after “ Murray et al.”), and Papandrinopoulou et al., Pulmonary Medicine. 2012, vol. 2012, article ID 542769, pp. 1-6 (herein after “Papandrinopoulou”).
Regarding claims 1, a method for treating emphysema in a mammal having an elevated level of lung compliance as compared to a comparable healthy mammal not having said emphysema, wherein said method comprises: (a) identifying said mammal as having emphysema, and (b) administering a composition comprising 1 x 10 8 to 1 x10 14 CFU of live or killed Prevotella to a respiratory system of said mammal, thereby reducing said elevated level of lung compliance to that of said comparable healthy mammal, wherein said Prevotella is Prevotella histicola or Prevotella melaninogenica:
Evelo teaches pharmaceutical compositions comprising Prevotella extracellular vesicles (EVs) (i.e., EVs generated by or isolated from bacteria of the genus Prevotella) useful for the treatment and/or prevention of disease (e.g., autoimmune disease, inflammatory disease), as well as methods of using such pharmaceutical compositions (e.g., for the treatment of autoimmune diseases, inflammatory diseases, either alone or in combination with other therapeutics) (see Evelo, pg. 1, para[2]), thereby constituting a method of treatment as recited in instant claim 1. The pharmaceutical compositions comprise both Prevotella EV and whole Prevotella bacteria (i.e., live bacteria, killed bacteria, attenuated bacteria)(see Evelo, pg. 1, para[2]), thereby constituting a composition comprising live or killed Prevotella as recited in instant claim 1. Evelo teaches that a subject or a patient described as “in need thereof” refers to one in need of a treatment for a disease (see Evelo, pg. 20, para[65]). Mammals (i.e., mammalian animals) include humans, laboratory animals (e.g., primates, rats, mice), livestock (e.g., cows, sheep, goats, pigs), and household pets (e.g., dogs, cats, rodents) (see Evelo, pg. 20, para[65]). In some of Evelo’s embodiments, administering the Prevotella/EVs is more effective at treating a subject than administering whole Prevotella bacteria of the same strain as the bacteria from which the Prevotella EVs were derived (See Evelo, pg. 6, para[6]); thereby constituting administering a composition to the mammal as recited in instant claim 1.
Evelo’s pharmaceutical compositions comprise Prevotella EVs and/or Prevotella bacteria of the species Prevotella histicola or Prevotella melaninogenica (See Evelo, pg. 21, para[68]), thereby constituting where the composition comprises Prevotella histicola and Prevotella melaninogenica as recited in instant claim 1. Evelo also teaches that while some mice receive EVs through i.v. injection, other mice may receive EV through intraperitoneal (i.p.) injection, subcutaneous (s.c.) injection, nasal route administration, oral gavage, or other means of administration (see Evelo, pg. 116, para[314]), thereby constituting where the composition is administered to a respiratory system of said mammal as recited in instant claim 1. Example 19 of Evelo’s work teaches Prevotella histicola Strain A and/or EVs in a mouse model, where mice were dosed for nine days as follows: oral administration of 1 x 109 CFU Prevotella histicola Strain A (see Evelo, pg. 125, para[351]); thereby constituting administering a composition comprising 1 x 10 8 to 1 x10 14 CFU, as recited in instant claim 1. Additionally, MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses by the prior art" a prima facie case of obviousness exists. Therefore, Evelo’s dose (i.e., 1 x 109 CFU) falls within the instantly claimed range of 1 x 10 8 to 1 x10 14 CFU of live or killed Prevotella.
Evelo does not expressly teach treating emphysema in a mammal, as recited in instant claim 1. However the methods and compositions described by Evelo, relate to the treatment or prevention of a disease or disorder associated with a pathological immune response, such as an inflammatory disease (See Evelo, pg. 83, para[180]). Evelo adds that the compositions can be used for preventing or treating an inflammatory disease such as a TNF-mediated inflammatory disease (e.g., an inflammatory lung disease, such as chronic obstructive pulmonary disease) (see Evelo, pg. 83, para[182]). Thereby, Evelo’s teachings read on a method for treating emphysema in a mammal.
Furthermore, it is noted that Evelo’s Fig. 1D illustrates the effects of extracellular vesicles of P. histicola on IL-1β (See Evelo, Fig. 1D). The results displayed in the figure were obtained after priming and challenging mice with KLH (keyhole limpet hemocyanin), removing the ears and homogenizing them to analyze the supernatant for IL-1β (See Evelo, pg. 127, para[356]). Mice that were treated with 10µg of P. histicola EVs (i.p.) showed levels of IL-1β comparable to that seen in the Dexamethasone group (positive control) (See Evelo, pg. 127, para[356]). The ability of an intra-peritoneally administered Prevotella histicola strain A-derived EVs in reducing expression of IL-1β 48 hours after antigen challenge in a KLH-based delayed type hypersensitivity mouse model is shown in Fig. 1D (See Evelo, pg. 7, para[12]). Therefore, Evelo demonstrates that Prevotella EVs reduces IL-1β.
Additionally, Lappalainen teaches that chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation throughout the airways, parenchyma, and pulmonary vasculature (See Lappalainen, pg. 311, left column paragraph 3). Chronic inflammation in the bronchi leads to remodeling of the airway wall, with increasing collagen content (See Lappalainen, pg. 311, left column paragraph 3). Destruction of the lung parenchyma leads to emphysema, defined as abnormal enlargement of the distal airspaces (See Lappalainen, pg. 311, left column paragraph 3). The early changes of emphysema include disruption of elastic fibers that then leads to the loss of the alveolar septa (See Lappalainen, pg. 311, left column paragraph 3). Lappalainen also teaches that the production of the inflammatory cytokine interleukin (IL-1) is increased in lungs of patients with chronic obstructive pulmonary disease (COPD) (See Lappalainen, pg. 311, Abstract). Induction of IL-1β expression in the lungs of adult mice caused pulmonary inflammation characterized by neutrophil and macrophage infiltrates (See Lappalainen, pg. 311, Abstract). IL-1β caused distal airspace enlargement, consistent with emphysema (See Lappalainen, pg. 311, Abstract). IL-1β caused disruption of elastin fibers in alveolar septa and fibrosis in airway walls and in the pleura (See Lappalainen, pg. 311, Abstract). IL-1β increased the thickness of conducting airways, enhanced mucin production, and caused lymphocytic aggregates in the airways (See Lappalainen, pg. 311, Abstract). Chronic production of IL-1β in respiratory epithelial cells of adult mice causes lung inflammation, enlargement of distal airspaces, mucus metaplasia, and airway fibrosis in the adult mouse (See Lappalainen, pg. 311, Abstract). Therefore, Lappalainen demonstrates a relationship between presence of inflammatory cytokine interleukin beta in lungs of patients with chronic obstructive pulmonary disease (COPD).
Furthermore, Lee teaches that emphysema is an autoimmune disease characterized by the presence of antielastin antibody and T-helper type 1 responses, which correlate with emphysema severity (see Lee, pg. 567, Abstract).Therefore, the teachings of Evelo when combined with the teachings of Lappalainen and Lee are suggestive of a method for treating emphysema in a mammal as recited in instant claim 1 because IL-1β causes disruption of elastin fibers in alveolar septa, fibrosis in airway walls and in the pleura, in addition to distal airspace enlargement; which are characteristic of destruction of the lung parenchyma which leads to emphysema. Therefore reducing IL-1β levels with Evelo’s pharmaceutical composition comprising Prevotella histicola or Prevotella melaninogenica would result in a method for treating emphysema in a mammal as recited in instant claim 1.
Evelo does not expressly teach a mammal having an elevated level of lung compliance as compared to a comparable healthy mammal not having said emphysema, nor reducing said elevated level of lung compliance to that of said comparable healthy mammal, as recited in instant claim 1.
However, Papandrinopoulou teaches that chronic obstructive pulmonary disease, namely, pulmonary emphysema and chronic bronchitis, is a chronic inflammatory response of the airways to noxious particles or gases (see pg. 1, left column, introduction). Chronic bronchitis and emphysema are entities of COPD and are characterized by (1) partial block of the lumen (e.g., due to excessive mucous production forming semisolid plugs), (2) thickening of the airway wall, which occurs because of edema or muscle hypertrophy, and (3) abnormality of the tissue surrounding the airways (destruction of the parenchyma and narrowing of the airway due to loss of radical traction) (see pg. 1, left column, introduction). Papandrinopoulou also teaches that the static mechanical properties of the respiratory system and its component parts are studied by determining the corresponding pressure-volume (P-V) relationships (see pg. 3, left column, paragraph 2). The P-V curves that are obtained as volume is changed in progressive steps from residual volume (RV) to total lung capacity (TLC) and back again are loops (see pg. 5, left column, paragraph 1). The elastic properties of the lung and chest wall as well as the changes in lung units between inflation and deflation are responsible for the presence of these loops (see pg. 5, left column, paragraph 1). The lung elasticity is depicted by the static volume-pressure curve and the fact that the P-V curve is nonlinear practically means that as lung volume increases, the elastic elements approach their limits of distensibility (see pg. 5, left column, paragraph 1). Papandrinopoulou adds that compliance is increased in obstructive lung disease like pulmonary emphysema, that the elastic recoil is decreased and the P-V curve is shifted up and left due to the loss of elastic tissue as a result of alveolar destruction (see pg. 4, right column, paragraph 2). As such, the teachings of Papandrinopoulou suggest that lung compliance is a parameter used to establish the condition of the lung and that emphysematous lungs exhibit an increase in lung compliance due to a loss in elastic recoil.
Murray et al. teach administering a composition comprising, or consisting essentially of live Prevotella histicola to the mammal under conditions wherein the severity of the autoimmune condition is reduced (see Murray et al., column 2, lines 14-18). The severity of the autoimmune condition can be reduced by greater than about 25% following the administration step (see Murray et al., column 2, lines 25-27 and claim 8). Murray et al. also teach that a composition containing P. histicola or P. histicola components can be used as a nutritional supplement to supplement a mammal’s diet with bacterial organisms having the ability to reduce the severity or development of an autoimmune condition (see Murray et al., column 7, lines 44-18). Therefore, an ordinary skill artisan would have been motivated with reasonable expectation of success to measure lung compliance as part of a method of treating emphysema in a mammal in order to determine the efficacy of the treatment.
It is acknowledged that Evelo does not expressly teach a method for treating emphysema in a mammal having an elevated level of lung compliance as compared to a comparable healthy mammal not having said emphysema, following said administering step, said elevated level of lung compliance is reduced to a level of lung compliance of said comparable healthy mammal. However, Evelo teaches compositions that can be used for preventing or treating (reducing, partially or completely, the adverse effects of) an autoimmune disease, such as a TNF-mediated inflammatory disease (e.g., an inflammatory lung disease, such as chronic obstructive pulmonary disease) (see Evelo, pg. 83, para[182]). Although Evelo does not expressly teach treating emphysema, there is a correlation between a TNF-mediated inflammatory disease (i.e., COPD) and emphysema because: production of the inflammatory cytokine interleukin (IL-1) is increased in lungs of patients with COPD; because IL-1β increased the thickness of conducting airways, enhanced mucin production, and caused lymphocytic aggregates in the airways; and because distal airspace enlargement caused by IL-1β is consistent with emphysema as taught by Lappalainen. Additionally, Lee teaches that emphysema is an autoimmune disease characterized by the presence of antielastin antibody and T-helper type 1 responses, which correlates with emphysema’s severity.
Since Evelo teaches the manipulative step for preventing or treating an autoimmune disease such as COPD, by administering a pharmaceutical composition comprising 1 x 109 CFU Prevotella histicola Strain A, and since lung compliance is increased in obstructive lung disease like pulmonary emphysema as taught by Papandrinopoulou; it would necessarily follow that the pharmaceutical composition of Evelo also treats emphysema in a mammal having an elevated level of lung compliance as compared to a comparable healthy mammal not having said emphysema. An ordinary skilled artisan would have been motivated with reasonable expectation of success to administered a composition comprising Prevotella in order to reduce lung compliance to a level comparable to the lung compliance of a healthy mammal because it was known that Prevotella EVs reduces IL-1β. And because it was also known that IL-1β causes disruption of elastin fibers in alveolar septa, fibrosis in airway walls and in the pleura, in addition to distal airspace enlargement; which are characteristic of destruction of the lung parenchyma which leads to emphysema.
Additionally, MPEP 2112-2112.02 states that when a reference discloses all the limitations of a claim except for a property or function, and the Examiner cannot determine whether or not the reference inherently possesses properties which render obvious the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, Evelo teaches pharmaceutical compositions comprising Prevotella useful for the treatment and/or prevention of an autoimmune disease, such as a TNF-mediated inflammatory disease (e.g., an inflammatory lung disease, such as chronic obstructive pulmonary disease). The Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not lung compliance in a mammal having emphysema is reduced from an elevated level to a lung compliance level of a healthy mammal not having said emphysema following administration of a composition comprising 1 x 10 8 to 1 x10 14 CFU of live or killed Prevotella to a respiratory system of said mammal having emphysema. The cited art taken as a whole demonstrates a reasonable probability that reduction in lung compliance following said administering step is either identical or sufficiently similar to the claimed reduction in lung compliance (i.e., reduction to a level of lung compliance of a comparable healthy mammal not having emphysema), and that whatever differences exists are not patentably significant. Therefore, with the showing of the reference, the burden of establishing novelty or non-obviousness by objective evidence is shifted to the Applicants.
From the teachings of the references, the Examiner recognizes that 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 follow the teachings of Evelo and administer a pharmaceutical composition comprising live or killed Prevotella histicola or Prevotella melaninogenica to a mammal in order to treat emphysema by reducing IL-1β levels where such administration also necessarily results in reducing lung compliance in a mammal having emphysema from an elevated level to a level of lung compliance of a comparable healthy mammal not having said emphysema. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so because: emphysema is known to be an autoimmune disease characterized by the presence of antielastin antibody and T-helper type 1 responses as taught by Lee; because chronic inflammation leads to remodeling of the airway wall and destruction of the lung parenchyma, and IL-1β was known to cause distal airspace enlargement consistent with emphysema as taught by Lappalainen; because a composition comprising P. histicola has the ability to reduce the severity or development of an autoimmune condition by greater than about 25% as taught by Murray; and because lung compliance is increased in obstructive lung disease like pulmonary emphysema due to loss in elastic recoil as a result of alveolar destruction and since the static mechanical properties of the respiratory system and its component parts are studied by determining the corresponding pressure-volume (P-V) relationships as taught by Papandrinopoulou. An ordinary skill artisan would have been motivated to determine the lung compliance of a comparable healthy mammal not having said emphysema as well as emphysematous lungs following administration of a composition comprising live or killed Prevotella.
One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that that the pharmaceutical composition comprising Prevotella of Evelo is useful for the treatment and/or prevention of autoimmune diseases and inflammatory diseases, either alone or in combination with other therapeutics and since it was known that Evelo’s composition comprising 1 x 109 CFU Prevotella histicola Strain A decreases IL-1β levels. Therefore, administering live or killed Prevotella to a mammal to reduce IL-1β levels would support a the instantly claimed method by constituting some teaching, suggestion or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention; and/or the use of a known technique to improve similar devises (methods, or products) in the same way; and/or the application of a known technique to a known device (method, or product) ready for improvement to yield predictable results pursuant to KSR.
Regarding claims 2-3, wherein the composition comprises live Prevotella as recited in instant claim 2; and wherein the composition comprises killed Prevotella and no live Prevotella as recited in instant claim 3:
As previously mentioned, Evelo teaches that the pharmaceutical compositions comprise both Prevotella EV and whole Prevotella bacteria (i.e., live bacteria, killed bacteria, attenuated bacteria)(See Evelo, pg. 1, para[2]), thereby constituting a composition comprising live or killed Prevotella as recited in instant claims 2-3.
Regarding claims 4 and 7, wherein said Prevotella comprises Prevotella melaninogenica as recited in instant claim 4; and wherein said Prevotella comprises Prevotella histicola as recited in instant claim 7:
Evelo’s pharmaceutical compositions comprise Prevotella EVs and/or Prevotella bacteria of the species Prevotella histicola or Prevotella melaninogenica (See Evelo, pg. 21, para[68]), thereby constituting where the composition comprises Prevotella melaninogenica as recited in instant claims 4 and 7.
Regarding claim 5, wherein said administering comprises intranasally administering:
Evelo refers to administration as to a route of administration of a composition to a subject, and provides examples of routes of administration which include inhalation (nasal) or injection, by inhalation or aerosol administration (See Evelo, pg. 9, para[31]). The pharmaceutical compositions described by Evelo can be administered in any form by any effective route, including but not limited to inhalation (See Evelo, pg. 9, para[31]); thereby constituting where administering comprises administration to the respiratory system since inhalation necessarily constitutes administration to the respiratory system as recited in instant claim 5.
Regarding claim 6, wherein the composition comprises 1 x 108 to 1 x 1010 CFU of Prevotella:
Evelo teaches that the number of Prevotella bacteria particles can be based on actual particle number or (if the bacteria is live) the number of CFUs (See Evelo, pg. 51, para[90]). Example 19 of Evelo’s work teaches Prevotella histicola Strain A and/or EVs in a mouse model, where mice were dosed for nine days as follows; oral administration of 1 x 109 CFU Prevotella histicola Strain A, and with an oral administration of 2.09 x108 CFU Prevotella melaninogenica (See Evelo, pg. 125, para[351]), thereby constituting wherein the composition comprises a specific amount that lies within the claimed range of 1 x 108 to 1 x 1010 CFU of Prevotella and of Prevotella melaninogenica as recited in instant claim 6.
Additionally, MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses by the prior art" a prima facie case of obviousness exists. 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) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%". The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.) Moreover, the Federal Circuit found that a prima facie case existed where a claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms and the prior art taught that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." In re Geisler, 116 F.3d 1465, 1469-82, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997). Therefore, the claimed CFU range of Prevotella would have been obvious to one of ordinary skill in the art since the prior art range (i.e., 1 x 109 CFU Prevotella histicola ) lies within the claimed CFU range of Prevotella (i.e., 1 x 108 to 1 x 1010). As such, the teachings of Evelo satisfy the claim limitations as recited in instant claim 6.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the above claims would have been obvious to one of ordinary skill in the art within the meaning of 35 U.S.C 103. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill before the effective filing date.
Applicants’ Arguments
Applicant asserts that the claimed invention is not obvious over the cited prior art, for the reasons of record even when considering the teachings of Papandrinopoulou et al. reference (see Remarks, filed 03/19/2026, pg. 2, last paragraph). Applicant argues that the presently presented claims have been amended and are commensurate in scope with the unexpected results presented, for example, in Fig. 5D and that the presently presented claims are patentable over the combination of cited references (see Remarks, filed 03/19/2026, pg. 3, first paragraph).
Response to Arguments
Applicant’s arguments filed on 03/19/2026, with respect to the 35 U.S.C. 103 rejection to claims 1-7, have been fully considered but are not persuasive.
Applicant disagrees to the rejected claims under 35 U.S.C 103 for the reasons of record (see Remarks, filed 09/24/2025, pg. 6 of 7). Applicants also assert that the newly added claim limitations to independent claim 1 (i.e., “having an elevated level of lung compliance as compared to a comparable healthy mammal not having said emphysema” and “thereby reducing said elevated level of lung compliance to that of said comparable healthy mammal”) are commensurate in scope with the unexpected results presented, for example in Figure 5D (see Remarks, filed 03/19/2026, pg. 3).
The reasons of record as stated in the action mailed on 08/22/2025 and in the action mailed on 10/30/2025 are herewith reiterated.
In response to Applicant’s first argument (i.e., the combination of cited references do not teach or suggest the claimed method for treating emphysema in a mammal), it is found unpersuasive.
A teaching, suggestion, or motivation to combine references that is found in the prior art is an appropriate rationale for determining obviousness. KSR, 550 U.S. at 418, 82 USPQ2d at 1396. In the instant case, the cited prior art, i.e., Evelo, teaches a method for the treatment of autoimmune diseases and inflammatory diseases such as COPD where the method comprises administering a composition comprising Prevotella bacteria of the species Prevotella histicola or Prevotella melaninogenica. Evelo also teaches where mice were dosed for nine days with an oral administration of 1 x 109 CFU Prevotella histicola Strain A, and with an oral administration of 2.09 x108 CFU Prevotella melaninogenica. Although Evelo does not expressly teach treating emphysema; the supporting prior art, i.e., Lappalainen and Lee, disclose a correlation between emphysema (i.e., an autoimmune disease) and COPD (i.e., chronic inflammation of the airways, parenchyma, and pulmonary vasculature). Additionally, the teachings of Murray suggest that the severity of the autoimmune condition can be reduced by greater than about 25% following the administration of a composition comprising live Prevotella histicola. Moreover, since the teachings of Papandrinopoulou suggest that lung compliance is a parameter used to establish the condition of the static mechanical properties of the respiratory system and its component parts by determining the corresponding pressure-volume relationships; and since lung compliance is increased in obstructive lung disease like pulmonary emphysema due to the loss of elastic tissue as a result of alveolar destruction, an ordinary skilled artisan would have been motivated by the teachings and suggestions of the cited prior art (i.e., Evelo, Lappalainen, Lee, Murray and Papandrinopoulou) to administer a composition comprising live or killed Prevotella to a respiratory system of a mammal having emphysema and to measure lung compliance following said administering step in order to determine the efficacy of the administered composition. An ordinary skilled artisan would also have been motivated to measure lung compliance in a healthy mammal not having emphysema as a way to measure/compare the effect of the composition administered to the mammal having emphysema. Since the cited prior art teaches that a composition comprising live Prevotella histicola can reduce the severity or development of an autoimmune condition by greater than about 25% (i.e., intended result of a process step positively recited) following the administration step, it must necessarily follow that lung compliance (i.e., intended result of a process step positively recited) is also reduced to a level of lung compliance of a comparable healthy mammal not having said emphysema. Therefore, the Examiner maintains that the combination of cited references teach or suggest motivation to administer a composition comprising 1 x 108 CFU to 1 x 1014 CFU live or killed Prevotella to a respiratory system of a mammal identified as having emphysema wherein lung compliance is reduced following said administration step to a level of lung compliance of a comparable healthy mammal not having said emphysema.
In response to Applicant’s second argument (i.e., a person having ordinary skill in the art reading the combination of cited references would not have had a reasonable expectation of success in reducing lung compliance by any degree), it is found unpersuasive.
As previously discussed in 35 U.S.C 103 rejection above, reduction in lung compliance from an elevated level to a level of lung compliance of a comparable healthy mammal not having emphysema is the intended result of a process step positively recited. In the instant case the process step positively recited constitutes a method of treating emphysema in a mammal, wherein said method comprises administering a composition comprising 1 x 108 CFU to 1 x 1014 CFU live or killed Prevotella to a respiratory system of said mammal, wherein said Prevotella is Prevotella histicola or Prevotella melaninogenica. As such, the inherent result of administering said composition is reduced lung compliance; therefore claim 1 recites an intended result that does not appear to render material to patentability. Additionally, a person having ordinary skill in the art reading the combination of cited references would have had a reasonable expectation of success in reducing lung compliance by any degree, given that the cited prior art (i.e., Murray et al) teaches that the severity of the autoimmune condition can be reduced by greater than about 25% following the administration step of a composition comprising or consisting essentially of live Prevotella histicola; and given that the cited prior art (i.e., Papandrinopoulou) teaches that lung elasticity is depicted by the static volume-pressure curve and lung compliance is increased in obstructive lung disease like pulmonary emphysema due to a decrease in elastic recoil as a consequence of loss of elastic tissue that results from alveolar destruction. As such, the Examiner maintains that an ordinary skilled artisan would have had a reasonable expectation of success in reducing an elevated level of lung compliance by any degree, in particular to a level of lung compliance of a comparable healthy mammal not having said emphysema, because the combination of cited references teach successfully reducing the severity of an autoimmune condition by greater than about 25% after administering a composition comprising Prevotella, and because lung compliance was known to be a parameter in determining pressure-volume (P-V) relationships corresponding to static mechanical properties of the respiratory system and its component parts.
In response to Applicant’s second argument (i.e., unexpected results, more specifically statistically significant reductions of lung compliance in mice exposed to cigarette smoke and treated intranasally with Prevotella histicola and Prevotella melaninogenica, respectively, as compared to untreated mice exposed to cigarette smoke), it is found unpersuasive.
Pursuant under MPEP 716.02(d), whether the unexpected results are the results of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” With respect to claim 1, the scope of the claimed method comprises administering a composition comprising 1 x 108 CFU to 1 x 1014 CFU of live or killed Prevotella to a respiratory system of said mammal, wherein said Prevotella is Prevotella melaninogenica, and wherein lung compliance is reduced, following said administering step, to a level of lung compliance of a comparable healthy mammal not having said emphysema. Thus, the scope of claim 1 encompasses administration of a composition comprising live or killed Prevotella histicola or Prevotella melaninogenica to a respiratory system of a mammal identified as having emphysema. When reviewing the evidence provided in the specification, the specification does not support details pertaining to the specifics of the composition (i.e., effective amount) that reduces lung compliance. Instead, the instant specification recites that any amount of a composition containing live or killed Prevotella (e.g., P. histicola or P. melaninogenica) can be administered to a mammal and that the components can depend on many factors including the desired results, that the components contained within a single dose can be an amount that effectively exhibits anti-inflammatory activity within the mammal, and that a composition containing live P. histicola and/or P. melaninogenica can be formulated in a dose such that a mammal receives between 10 and 1014 microorganisms (see instant specification, pg. 27, lines 27-34 and pg. 28, lines 1-2 and lines 3-19).
Additionally, it is noted that Example 7, on pp. 48-49 and Example 12, on pp. 51-52 of the instant specification, are the only examples that recite treating mice exposed to cigarette smoke with 10^9 CFU/100 µL of live Prevotella histicola or Prevotella melaninogenica suspended in 100 microliters of TSB (anaerobic) bacterial culture (see pg. 48, line 22 and pg. 52, line 13). It is also acknowledged that Example 12 demonstrates evidence of statistically significant loss of lung function with increased compliance indicative of emphysema or COPD in untreated mice (i.e., data shown in Figs. 5A and 5D) compared to mice exposed to cigarette smoke and treated with P. histicola intranasally (CS/PH) (i.e., data shown in Figs. 5B and 5D) as well as mice exposed to cigarette smoke and treated with P. melaninogenica intranasally (CS/PM) (i.e., Figs. 5C and 5D). However, from the information disclosed in Example 12, it is not readily apparent that the unexpected percentage in reduction to a level of lung compliance of a healthy mammal not having said emphysema demonstrated in Fig. 5D can be achieved by treating mice exposed to cigarette smoke with 1 x 108 CFU to 1 x 1014 CFU of a composition containing live or killed Prevotella (e.g., P. histicola or P. melaninogenica), nor that a composition containing live P. histicola and/or P. melaninogenica can be formulated in a dose such that a mammal receives between 1 x 108 CFU to 1 x 1014 CFU of Prevotella.
Additionally, MPEP 716.02(d)(I), states that [t]he nonobviousness of a broader claimed range can be supported by evidence based on unexpected results from testing a narrower range if one of ordinary skill in the art would be able to determine a trend in the exemplified data which would allow the artisan to reasonably extend the probative value thereof. In re Kollman, 595 F.2d 48, 201 USPQ 193 (CCPA 1979). MPEP 716.02(d)(II) also states that [t]o establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960). Therefore, the objective evidence of nonobviousness is not commensurate in scope with the invention as recited in instant claim 1.
Although Example 20 and Example 21 on pg. 55, lines 1-15 of the instant specification teach treating a human diagnosed with pneumonia or displaying one or more symptoms thereof (e.g., emphysema) with the composition comprising live P. histicola administered orally (see Example 20) and administered nasally (see Example 21), with a dose of about 1 x 103 to about 1 x 1014 CFU once a day for 8 weeks; and that the human is monitored to confirm reduction of one or more symptoms. However, it is not readily apparent which lung function parameter(s) (i.e., lung function compliance, lung volume, airway resistance, elastance or a combination thereof (see instant specification, pg. 3, lines 29-31)) indicative of emphysema or COPD are being treated. The instant specification is silent about reduction of one or more symptoms of pneumonia, emphysema or COPD, more specifically reduction in lung compliance to a level of lung compliance of a comparable mammal not having said emphysema.
Lastly and most importantly, pursuant to MPEP 716.02(c)(II), expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967). In other words, Applicant’s results depicted in Fig. 5D and Example 12 (see instant specification, pg. 52, lines 1-4) are expected because as previously discussed, it was known that a composition comprising 1 x 109 CFU Prevotella reduces IL-1β as taught by Evelo, and since lung compliance is increased in obstructive lung disease like pulmonary emphysema as taught by Papandrinopoulou; it would necessarily follow that a composition comprising Prevotella also reduces elevated levels of lung compliance in DQ8 mice exposed to cigarette smoke to a level of lung compliance of naïve DQ8 mice exposed to air only (i.e., a comparable healthy mammal not having said emphysema). Thus, Applicant’s results are expected and are also evidence of obviousness.
Accordingly, the 35 U.S.C 103 rejection to claims 1-7 is maintained.
Conclusion
No claims are allowed.
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/CLAUDIA ESPINOSA/Patent Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
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