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 .
Status of Claims
Claims 1, 6-9, 16, 24, 28-31, 33 and 40-60 are pending following the Reply filed 07/24/2026. Claims 17, 19-21, 25, 35 and 39 have been cancelled. Claims 1, 7, 8, 16, 24, 29 and 33 have been amended and claims 41-60 have been added without introducing new matter. All pending claims have been examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) filed 07/24/2026 has been considered by the examiner.
Withdrawn
Any objection or rejection of claims 17, 19-21, 25, 35 or 39 is moot because the claims have been cancelled.
The objection to claim 8 is withdrawn in light of the amendments.
Drawings
Applicant has submitted color drawings to overcome the objection set forth in the previous office action, and the color drawings appear to address the issues raised in the objection. However, the petition to accept color drawings is still pending at the time of this office action. Therefore, the objection to the drawings is hereby maintained until a petition filed under 37 CFR 1.84(a)(2) has been granted.
Color photographs and color drawings are not accepted in utility applications unless a
petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the
appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as
appropriate, if submitted via the USPTO patent electronic filing system or three sets of color
drawings or color photographs, as appropriate, if not submitted via the via USPTO patent
electronic filing system, and, unless already present, an amendment to include the following
language as the first paragraph of the brief description of the drawings section of the
specification:
The patent or application file contains at least one drawing executed in color. Copies of
this patent or patent application publication with color drawing(s) will be provided by the Office
upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and
black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 6-9 and 41-50 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of a natural product without significantly more. The rationale for this determination is explained below and is in keeping with the latest guidance regarding analysis of judicially excepted subject matter.
Subject Matter Eligibility Guidance
A three-step inquiry has been established to determine subject matter eligibility under 35 U.S.C. 101, in accordance with MPEP § 2106:
Step 1 – Is the claim directed to a process, machine, manufacture, or composition of matter?
Step 2A – Is the claim directed to a law of nature, natural phenomenon (product of nature), or an abstract idea? This is a two-prong inquiry:
Step 2A, prong 1 – Does the claim recite a law of nature, natural phenomenon, or an abstract idea?
Product of Nature Definition
When a law of nature or natural phenomenon is claimed as a physical product, the courts have often referred to the exception as a "product of nature". See Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 580, 106 USPQ2d 1972, 1975 (2013); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 758-59, 113 USPQ2d 1241, 1243 (Fed. Cir. 2014). As explained in those decisions, products of nature are considered to be an exception because they tie up the use of naturally occurring things, but they have been labeled as both laws of nature and natural phenomena. See Myriad Genetics, Inc., 569 U.S. at 590-91, 106 USPQ2d at 1979.
The Markedly Different Characteristics Analysis
The first step in the analysis is to select the appropriate counterpart to the nature-based product. When the nature-based product is derived from a naturally occurring thing, then the naturally occurring thing is the counterpart. See MPEP § 2106.04(c)(II)(A).
The second step in the analysis is to identify appropriate characteristics to compare. Appropriate characteristics must be possessed by the claimed product, because it is the claim that must define the invention to be patented. Cf. Roslin, 750 F.3d at 1338, 110 USPQ2d at 1673. See MPEP § 2106.04(c)(II)(B).
The final step in the markedly different characteristics analysis is to compare the characteristics of the claimed nature-based product to its naturally occurring counterpart in its natural state, in order to determine whether the characteristics of the claimed product are markedly different. See MPEP § 2106.04(c)(II)(C).
Step 2A, prong 2 – If the claim recites a judicial exception, does it recite additional elements that integrate the judicial exception into a practical application?
Limitations that are indicative of integration into a practical application include:
Improvements to the functioning of a computer, or to any other technology or technical field. See MPEP § 2106.05(a);
Applying the judicial exception with, or by use of, a particular machine. See MPEP § 2106.05(b);
Effecting a transformation or reduction of a particular article to a different state or thing. See MPEP § 2106.05(c);
Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. See MPEP § 2106.05(d);
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception. See MPEP § 2106.05(e).
Step 2B – If the recited judicial exception is not integrated into a practical application, does the claim recite additional elements that amount to significantly different than the judicial exception such that they provide an inventive concept? This step includes evaluation of the same considerations under Step 2A, Prong 2, as well as two additional considerations:
Adding a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field, which is indicative that an inventive concept may be present; and
Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, which is indicative that an inventive concept may not be present.
Analysis
Step 1: It must first be determined if the claim is to a statutory category and, if so, proceed to step 2A, prong 1.
The claims are directed to a pharmaceutical formulation comprising probiotic strain(s) and a pharmaceutically acceptable carrier, and fall within the statutory category of a composition of matter.
Step 2A, prong 1: Prong 1 requires the Examiner to evaluate whether the claim recites a judicial exception and, if so, proceed to prong 2.
Independent claim 1 recites that the pharmaceutical formulation comprises a “biotherapeutic” comprising either (i) a probiotic strain of Corynebacterium or (ii) a consortium of probiotics comprising at least one strain of Corynebacterium, and at least one pharmaceutically acceptable carrier.
Biotherapeutic: Given its plain meaning, the term “biotherapeutic” merely denotes that the formulation contains therapeutic compound(s) derived from living organisms, which includes the living organisms themselves. In the instant case, this term does not add any further structural limitation to the formulation beyond the recited probiotic strains themselves.
Probiotic: The term “probiotic” is defined in the instant specification as referring to a microorganism such as a bacteria or yeast that is associated with a positive effect for and/or confers an advantage to a subject (see pg. 9, para. [0037]). Unless otherwise specified by the claims, “probiotics” include microorganisms isolated from nature, which are natural products.
Corynebacterium: The specification states that Corynebacterium is a diverse bacterial genus that includes common residents of the upper respiratory tracts, skin and gastrointestinal tracts of humans and animals; although more than 150 species of Corynebacterium have been identified to date, the most common species isolated from the human respiratory tract are C. accolens, C. pseudodiptheriticum, C. propinquum, C. striatum, and C. tuberculostearicum (see pg. 122, para. [0377]).
Consortium: The specification states that probiotic can comprise “a consortium” of bacterial strains from the same genus or species (e.g., Corynebacterium sp.) or a consortium of bacterial strains of different genera or species (see pg. 9, para. [0037]).
In view of the above, the “probiotic” or “consortium of probiotics” of the claim are disclosed as including naturally occurring bacteria (e.g., Corynebacterium) isolated from their environment (e.g., human/animal hosts), and are natural products.
Pharmaceutically acceptable carrier: The specification states that the term “pharmaceutically acceptable carrier” includes sterile aqueous solutions, examples of which include “water” (see pg. 13, para. [0047]). Hence, this limitation also includes natural products (e.g., water).
Markedly different characteristics: In view of the above, the minimal structure required by claim 1 may be met by one or more naturally-occurring bacteria in the presence of water. It is apparent that the bacteria and water are natural products which commonly occur together in their natural environment. Therefore, per MPEP 2106.04(c)(I), there is no need to perform the markedly difference characteristics analysis, because the limitations themselves, even in combination, are by definition directed to a naturally occurring product.
Regarding the limitation of “wherein the strain or at least one of the strains from the bacterial genus Corynebacterium exhibits activity that inhibits Streptococcus pneumoniae in the respiratory system of a subject”. This newly added claim limitation is directed to an inherent property of the claimed bacterium, as evidenced by the prior art discussed under 35 U.S.C. 102 and 103. As it is well known in the art for these bacteria to exist in the respiratory system, i.e., their natural habitat, and for their presence as having the effect of inhibiting and excluding more harmful bacteria, such as Streptococcus pneumoniae, this function cannot be said to amount to a markedly different characteristic compared to its natural counterparts.
Thus, claim 1 is directed to the product of nature exception.
Claim 6, depending from claim 1, recites the further limitation, wherein the consortium of probiotics further comprises at least one strain from each of the bacterial genera, Dolosigranulum, Streptococcus, and Lactobacillus. In Example 2 of the specification, Corynebacterium, Dolosigranulum, Streptococcus, and Lactobacillus were identified in infant nasopharyngeal samples as part of Applicant’s study (see pg. 110, para. [0349], Table 4). Hence, similar to claim 1, the bacterial genera recited in claim 6 include naturally-occurring products (commensal bacteria), which have been found to occur together in their natural environment (the respiratory system). Thus, for the reasons discussed regarding claim 1, claim 6 is still directed to the judicial exception.
Claim 7, depending from claim 1, recites the further limitation, “wherein the strain or the at least one strain from the bacterial genus Corynebacterium comprises C. tuberculostearicum… C. accolens… or C. striatum… … or any combination thereof”. As discussed regarding claim 1, the recited strains are among the most common species of Corynebacterium isolated from the human respiratory tract. Thus, claim 7 is still directed to the judicial exception.
Claim 8, depending from claim 1, recites the further limitation, wherein the biotherapeutic comprises at least 103 or up to at least 1012 CFUs of the probiotic(s). Here, the mere quantity of bacteria in in the composition is not sufficient, on its own, to distinguish it from a product of nature, particularly because higher quantities can be the natural result of bacterial growth, which is an inherent characteristic of the bacterium. Therefore, compared to a Corynebacterium strain occurring in its natural environment (i.e., the closest natural counterpart) any increase in quantity is, at best, an incidental change resulting from this inherent characteristic. See MPEP 2106.04(c)(II)(C). Thus, claim 8 is still directed to the judicial exception.
Claim 9, depending from claim 6, recites the further limitation, wherein the consortium comprises the strains of the four recited bacterial genera in a ratio of “1:0.01:0.01:0.01 to about “1:1:1:1”. In Example 2 of the specification, Corynebacterium, Dolosigranulum, Streptococcus, and Lactobacillus comprised 4.6%, 1.3%, 4.1%, and 1.7%, respectively, of the total bacterial genera identified in infant nasopharyngeal samples (see pg. 110, para. [0349], Table 4). Hence, the relative abundance of these bacterial genera in their natural environment is within the scope of the claim. Furthermore, as discussed regarding claim 8, the growth of the bacteria is an inherent characteristic of the bacteria in nature, and the relative abundance of the bacteria in the formulation is merely an incidental change resulting from this inherent characteristic. Thus, claim 9 is still directed to the judicial exception.
Claim 41 recites the pharmaceutical formulation of claim 7, wherein the strain comprises at least one of Corynebacterium strains 05-144, 05-104, and 05-122. The specification does not specifically disclose how these strains were obtained, but Applicant’s examples do disclose the isolation of Corynebacterium strains from infant nasopharyngeal samples (see pg. 107, para. [0344]) and the inventors disclose these Corynebacterium species to be commonly cultured from the human respiratory tract (see pg. 128, para. [0396]). Therefore, these strains appear to have been isolated from nature, there is no evidence of them having been modified from the naturally occurring strains from which they were derived, and their properties (e.g., inhibition of Streptococcus) are natural characteristics of the bacteria as they were found in nature. Therefore, claim 41 is still directed to the judicial exception.
Claims 42-44 recite the bacterial strains as being from species, such as C. propinquum, C. pseudodiptheriticum, or C. glutamicum. All of these species are disclosed as being derived from infant nasopharyngeal samples and include natural products. Therefore, claims 42-44 are still directed to the judicial exception.
Claims 45-50 recite further functional limitations which are inherent properties of the naturally occurring bacteria as evidenced by the prior art discussed under 35 U.S.C. 102 and 103. It well known in the art for these bacteria to exist in the respiratory system, i.e., their natural habitat, and for their presence as having the effect of inhibiting and excluding other more harmful bacteria, such as Streptococcus pneumoniae, this function cannot be said to amount to a markedly different characteristic in the claimed microorganism compared to its natural counterparts. There is no evidence that the underlying mechanisms recited in the claims (e.g., inhibition of adherence of Streptococcus pneumoniae to respiratory epithelium) are not present in the naturally occurring bacteria. In fact, the disclosure does not disclose any Corynebacterium strains that were obtained by any means other than isolating them from their natural environment (i.e., the respiratory tract). Thus, these functional limitations are directed to the mere observation of these properties as they occur in the naturally occurring strains. Therefore, claims 45-50 are still directed to the judicial exception.
Step 2A, prong 2; Step 2B: In the instant case, claims 1 and 6-9 recite natural products (i.e., probiotics, carriers that include water) without any additional elements to evaluate under Step 2A, prong 2 or Step 2B. Hence, there are no elements beyond the naturally occurring product to integrate the judicial exception into a practical application or that amount to significantly more than the judicial exception.
Therefore, the claims are directed to natural products (Step 2A, Prong two) and do not recite any additional elements that amount to significantly more (Step 2B).
In conclusion, claims 1, 6-9 and 41-50 are directed to a judicial exception and do not qualify as eligible subject matter under 35 U.S.C. § 101.
Claim Rejections - 35 USC § 112(a) - Enablement
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 41 and 51 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Availability of Biological Material
Every patent must contain a written description of the invention sufficient to enable a person skilled in the art to which the invention pertains to make and use the invention. Where the invention involves a biological material and words alone cannot sufficiently describe how to make and use the invention in a reproducible manner, access to the biological material may be necessary for the satisfaction of the statutory requirements for patentability under 35 U.S.C. 112.
In the instant case, the claims recite Corynebacterium tuberculostearicum strain 05-144, Corynebacterium coyleae strain 05-104 and Corynebacterium accolens strain 05-122. While these appear to be strains that were used in Applicant’s examples, the specification does not describe any process to obtain them or characteristic(s) to identify them. Furthermore, their designations (i.e., “05-144”, “05-104”, “05-122”) do not appear in the prior art of record, and there does not appear to be any strain(s) having these designations that are available to the public
It is apparent that Corynebacterium tuberculostearicum strain 05-144, Corynebacterium coyleae strain 05-104 and Corynebacterium accolens strain 05-122 are required to practice the claimed invention, because they are necessary limitations for the success of the invention as recited in the claims above. As required elements they must be known and readily available to the public or obtainable by a repeatable method set forth in the specification. If they are not so obtainable or available, the enablement requirements of 35 U.S.C. § 112, first paragraph, may be satisfied by a deposit of strains 05-144, 05-104 and 05-122. See 37 CFR 1.802. One cannot practice the claimed invention or determine whether a Corynebacterium strain has the necessary characteristics without access to strains 05-144, 05-104 and 05-122.
Deposit of Corynebacterium tuberculostearicum strain 05-144, Corynebacterium coyleae strain 05-104 and Corynebacterium accolens strain 05-122 in a recognized deposit facility would satisfy the enablement requirements of 35 U.S.C. 112., because the strains would be readily available to the public to practice the invention claimed. However, further conditions must also be met in order to meet the deposit requirement. See 37 CFR 1.801- 37 CFR 1.809.
If a deposit is made under the terms of the Budapest Treaty, then an affidavit or declaration by applicants or someone associated with the patent owner who is in a position to make such assurances, or a statement by an attorney of record over his or her signature, stating that the deposit has been made under the terms of the Budapest Treaty and that all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of a patent, would satisfy the deposit requirements. See 37 CFR 1.808.
If a deposit is not made under the terms of the Budapest Treaty, then an affidavit or declaration by applicants or someone associated with the patent owner who is in a position to make such assurances, or a statement by an attorney of record over his or her signature, stating that the deposit has been made at an acceptable depository and that the following criteria have been met:
(a) during the pendency of this application, access to the invention will be afforded to one determined by the Commissioner to be entitled thereto;
(b) all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon granting of the patent;
(c) the deposit will be maintained for a term of at least thirty (30) years and at least five (5) years after the most recent request for the furnishing of a sample of the deposited material;
(d) a viability statement in accordance with the provisions of 37 CFR 1.807; and
(e) the deposit will be replaced should it become necessary due to inviability, contamination or loss of capability to function in the manner described in the specification.
In addition, the identifying information set forth in 37 CFR 1.809(d) should be added to the specification. These include: (1) The accession number of the deposit; (2) The date of the deposit; (3) A description of the deposited biological material sufficient to specifically identify it and to permit examination; and (4) The name and address of the depository.
See 37 CFR 1.803 - 37 CFR 1.809 for additional explanation of these requirements.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 7-8, 16, 29-31, 33, 40, 42-50 and 52-60 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Zhou, et al. (US 2022/0202879 A1; effectively filed 12/15/2020; previously cited), hereafter, “Zhou”.
Regarding claim 1, Zhou’s disclosure relates to methods and compositions utilizing upper-airway microbiota for diagnosing individuals at risk for asthma, and further to probiotic compositions and methods for treating asthma by administering microorganisms that are associated with decreased risk of asthma exacerbations (see Abstract). Zhou teaches a probiotic formulation for preventing, delaying or attenuating asthma exacerbations comprising a pharmaceutically acceptable unit dose of a probiotic composition comprising one or more isolated microorganisms selected from the genus Corynebacterium, genus Dolosigranulum, or a combination thereof, and a pharmaceutically acceptable carrier (see pg. 5, para. [0108]). Hence, Zhou teaches all of the structural limitations of independent claim 1.
Regarding the functional limitation of “wherein the strain… from the bacterial genus Corynebacterium exhibits activity that inhibits Streptococcus pneumoniae in the respiratory system of a subject”, Zhou teaches that “Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products that may prevent nasal colonization with Streptococcus” (see pg. 23, para. [0274]). Zhou teaches that administering Corynebacterium effectively treats respiratory infections in individuals whose nasal microbiome is characterized by an elevated abundance of Streptococcus pneumoniae (see pg. 21, para. [0258]). Therefore, this limitation is directed to an inherent property of the Corynebacterium that does not affect the structure of the claimed formulation. As Zhou teaches the same composition as the instant claims, the properties said composition are presumed to be inherent and the claimed method is anticipated.
Regarding claim 7, Zhou teaches the microorganisms of genus Corynebacterium comprise C. accolens (see pg. 5, para. [0109]).
Regarding claim 8, Zhou teaches that a suitable dose of the probiotic bacteria is from about 1x103 to about 1x1011 CFUs (see pg. 18, para. [0240]).
Regarding claim 16, Zhou teaches a method of treating an individual with a nasal microbiome characterized by an elevated abundance or proportion relative to a reference sample of Streptococcus pneumoniae, the method comprising administering to the individual a probiotic composition comprising an isolated microorganism, wherein the isolated microorganism is a microorganism of genus Corynebacterium, thereby preventing, delaying or attenuating an asthma exacerbation of the individual (see pg. 21, para. [0256]). Zhou teaches that the microorganisms described herein may be administered in a pharmaceutical formulation containing one or more pharmaceutically-acceptable carriers (see pg. 18, para. [0237]).
Regarding claim 29, Zhou teaches the method wherein the Corynebacterium is Corynebacterium accolens (see pg. 21, para. [0256]).
Regarding claim 30, Zhou teaches that a suitable dose of the probiotic bacteria is from about 1x103 to about 1x1011 CFUs (see pg. 18, para. [0240]).
Regarding claim 31, Zhou teaches the method includes administering one or more antimicrobial agents, to treat a concurrent asthma infection, if present, such as an antibacterial effective against Streptococcus, wherein the antibacterial agent is penicillin (see pg. 17, para. [0220]-[0223]).
Regarding claim 33, regarding the functional limitation of “wherein… the relative abundance of Streptococcus pneumoniae in the subject’s microbiome is decreased”, Zhou teaches that “Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products that may prevent nasal colonization with Streptococcus” (see pg. 23, para. [0274]). Zhou teaches that administering Corynebacterium effectively treats respiratory infections in individuals whose nasal microbiome is characterized by an elevated abundance of Streptococcus pneumoniae (see pg. 21, para. [0258]). Therefore, this limitation is directed to an inherent property of administering the Corynebacterium that does not affect the structure or steps of the claimed invention. As Zhou teaches the same process of administering the same composition as the instant claims, the effects and properties of administering said composition are presumed to be inherent and the claimed method is anticipated.
Regarding claim 40, Zhou teaches the composition is formulated for nasal administration (see pg. 5, para. [0113]) and is administered to the nasal cavity (see pgs. 17-18, para. [0230]).
Regarding claim 42, Zhou teaches that any species of the Corynebacterium genus is encompassed by the compositions of the disclosure, including C. propinquum (see pg. 7, paras. [0138]-[0139]).
Regarding claim 43, Zhou teaches that any species of the Corynebacterium genus is encompassed by the compositions of the disclosure, including C. pseudodiptheriticum (see pg. 7, paras. [0138]-[0139]).
Regarding claim 44, Zhou teaches that any species of the Corynebacterium genus is encompassed by the compositions of the disclosure, including C. afermentans (see pg. 7, paras. [0138]-[0139]).
Regarding claim 45, the further limitation of the claim is directed to an inherent property of the Corynebacterium. Zhou teaches that “Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products that may prevent nasal colonization with Streptococcus” (see pg. 23, para. [0274]). Zhou teaches that administering Corynebacterium effectively treats respiratory infections in individuals whose nasal microbiome is characterized by an elevated abundance of Streptococcus pneumoniae (see pg. 21, para. [0258]). As the claim recites no further structure, the further functional limitation of the claim must necessarily be present in the formulation of claim 1.
Regarding claim 46, the further limitation of the claim is directed to an inherent property of the Corynebacterium. Zhou teaches that “Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products that may prevent nasal colonization with Streptococcus” (see pg. 23, para. [0274]). Zhou teaches that administering Corynebacterium effectively treats respiratory infections in individuals whose nasal microbiome is characterized by an elevated abundance of Streptococcus pneumoniae (see pg. 21, para. [0258]). As the claim recites no further structure, the further functional limitation of the claim must necessarily be present in the formulation of claim 1.
Regarding claim 47, the further limitation of the claim is directed to an inherent property of the Corynebacterium. Zhou teaches that “Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products that may prevent nasal colonization with Streptococcus” (see pg. 23, para. [0274]). Zhou teaches that administering Corynebacterium effectively treats respiratory infections in individuals whose nasal microbiome is characterized by an elevated abundance of Streptococcus pneumoniae (see pg. 21, para. [0258]). As the claim recites no further structure, the further functional limitation of the claim must necessarily be present in the formulation of claim 1.
Regarding claim 48, the further limitation of the claim is directed to an inherent property of the Corynebacterium. Zhou teaches that “Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products that may prevent nasal colonization with Streptococcus” (see pg. 23, para. [0274]). Zhou teaches that administering Corynebacterium effectively treats respiratory infections in individuals whose nasal microbiome is characterized by an elevated abundance of Streptococcus pneumoniae (see pg. 21, para. [0258]). As the claim recites no further structure, the further functional limitation of the claim must necessarily be present in the formulation of claim 1.
Regarding claim 49, the further limitation of the claim is directed to an inherent property of the Corynebacterium. Zhou teaches that “Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products that may prevent nasal colonization with Streptococcus” (see pg. 23, para. [0274]). Zhou teaches that administering Corynebacterium effectively treats respiratory infections in individuals whose nasal microbiome is characterized by an elevated abundance of Streptococcus pneumoniae (see pg. 21, para. [0258]). As the claim recites no further structure, the further functional limitation of the claim must necessarily be present in the formulation of claim 1.
Regarding claim 50, the further limitation of the claim is directed to an inherent property of the Corynebacterium. Zhou teaches that “Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products that may prevent nasal colonization with Streptococcus” (see pg. 23, para. [0274]). Zhou teaches that administering Corynebacterium effectively treats respiratory infections in individuals whose nasal microbiome is characterized by an elevated abundance of Streptococcus pneumoniae (see pg. 21, para. [0258]). As the claim recites no further structure, the further functional limitation of the claim must necessarily be present in the formulation of claim 1.
Regarding claim 52, Zhou teaches the method wherein the Corynebacterium is C. propinquum (see pg. 21, para. [0256]).
Regarding claim 53, Zhou teaches the method wherein the Corynebacterium is C. pseudodiptheriticum (see pg. 21, para. [0256]).
Regarding claim 54, Zhou teaches that any species of the Corynebacterium genus is encompassed by the methods of the disclosure, including C. afermentans (see pg. 7, paras. [0138]-[0139]).
Regarding claim 55, the further limitation of the claim is directed to an inherent property of administering the Corynebacterium. Zhou teaches that “Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products that may prevent nasal colonization with Streptococcus” (see pg. 23, para. [0274]). Zhou teaches that administering Corynebacterium effectively treats respiratory infections in individuals whose nasal microbiome is characterized by an elevated abundance of Streptococcus pneumoniae (see pg. 21, para. [0258]). As the claim recites no further steps or structure, the further functional limitation of the claim must necessarily be present in the method of claim 16.
Regarding claim 56, the further limitation of the claim is directed to an inherent property of administering the Corynebacterium. Zhou teaches that “Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products that may prevent nasal colonization with Streptococcus” (see pg. 23, para. [0274]). Zhou teaches that administering Corynebacterium effectively treats respiratory infections in individuals whose nasal microbiome is characterized by an elevated abundance of Streptococcus pneumoniae (see pg. 21, para. [0258]). As the claim recites no further steps or structure, the further functional limitation of the claim must necessarily be present in the method of claim 16.
Regarding claim 57, the further limitation of the claim is directed to an inherent property of administering the Corynebacterium. Zhou teaches that “Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products that may prevent nasal colonization with Streptococcus” (see pg. 23, para. [0274]). Zhou teaches that administering Corynebacterium effectively treats respiratory infections in individuals whose nasal microbiome is characterized by an elevated abundance of Streptococcus pneumoniae (see pg. 21, para. [0258]). As the claim recites no further steps or structure, the further functional limitation of the claim must necessarily be present in the method of claim 16.
Regarding claim 58, the further limitation of the claim is directed to an inherent property of administering the Corynebacterium. Zhou teaches that “Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products that may prevent nasal colonization with Streptococcus” (see pg. 23, para. [0274]). Zhou teaches that administering Corynebacterium effectively treats respiratory infections in individuals whose nasal microbiome is characterized by an elevated abundance of Streptococcus pneumoniae (see pg. 21, para. [0258]). As the claim recites no further steps or structure, the further functional limitation of the claim must necessarily be present in the method of claim 16.
Regarding claim 59, the further limitation of the claim is directed to an inherent property of administering the Corynebacterium. Zhou teaches that “Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products that may prevent nasal colonization with Streptococcus” (see pg. 23, para. [0274]). Zhou teaches that administering Corynebacterium effectively treats respiratory infections in individuals whose nasal microbiome is characterized by an elevated abundance of Streptococcus pneumoniae (see pg. 21, para. [0258]). As the claim recites no further steps or structure, the further functional limitation of the claim must necessarily be present in the method of claim 16.
Regarding claim 60, the further limitation of the claim is directed to an inherent property of administering the Corynebacterium. Zhou teaches that “Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products that may prevent nasal colonization with Streptococcus” (see pg. 23, para. [0274]). Zhou teaches that administering Corynebacterium effectively treats respiratory infections in individuals whose nasal microbiome is characterized by an elevated abundance of Streptococcus pneumoniae (see pg. 21, para. [0258]). As the claim recites no further steps or structure, the further functional limitation of the claim must necessarily be present in the method of claim 16.
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.
Claim(s) 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhou.
Regarding claim 24, Zhou teaches a method comprising (a) acquiring a biological sample from an upper airway of an individual with asthma, who are asymptomatic or symptomatic, (b) identifying a plurality of microorganisms in the biological sample, and (c) determining an amount, concentration, or proportion of a microorganism in the biological sample, wherein the microorganism in the biological sample is Streptococcus pneumoniae (see pg. 20, para. [0247]). Zhou further teaches a method of treating an individual with a nasal microbiome characterized by an elevated abundance or proportion of Streptococcus pneumoniae relative to a reference sample, the method comprising administering to the individual a probiotic composition comprising an isolated microorganism, wherein the isolated microorganism is a microorganism of genus Corynebacterium, thereby preventing, delaying or attenuating an asthma exacerbation of the individual (see pg. 21, para. [0256]). Zhou teaches that “Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products that may prevent nasal colonization with Streptococcus” (see pg. 23, para. [0274]). Zhou teaches that the probiotic agents can be administered in a pharmaceutical composition further comprising one or more pharmaceutically acceptable excipients (see pg. 17, para. [0228]), and the microorganisms described herein may be administered in a pharmaceutical formulation containing one or more pharmaceutically-acceptable carriers (see pg. 18, para. [0237]).
Therefore, it would have been obvious to have monitored the relative abundance of Streptococcus pneumoniae in a biological sample obtained from the subject, because Zhou teaches the administration of Corynebacterium and Dolosigranulum to have the effect of inhibiting Streptococcus and teaches methods of (1) obtaining a biological sample to detect the proportion of Streptococcus pneumoniae and (2) determining the relative abundance of Streptococcus pneumoniae compared to a reference sample, as well as administrating the probiotics to inhibit the S. pneumoniae in the subject’s upper airway. Thus, a person of skill would have immediately envisaged combining these embodiments of Zhou’s disclosure in order to effectively treat asthma exacerbated by the presence of Streptococcus pneumoniae.
Claim(s) 6 and 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhou as applied to claims 1, 7-8, 16, 24, 29-31, 33, 40, 42-50 and 52-60 above, and further in view of De Grandi, et al. (previously cited), hereafter, “Grandi”.
Regarding claim 6, Zhou teaches the probiotic formulation comprising probiotic strains of Corynebacterium and Dolosigranulum, and a pharmaceutically acceptable carrier, as discussed above. Zhou also teaches the method further comprising administering a second probiotic composition comprising a bacterium from the genus Lactobacillus (see pg. 17, para. [0218]). Zhou teaches that airway microbiota dominated by Corynebacterium and Dolosigranulum are associated with favorable clinical outcomes compared to microbiota dominated by one more pathogenic Streptococcus and Staphylococcus bacteria (see pg. 1, para. [0006]), and increased abundance of Streptococcus pneumoniae and Staphylococcus aureus is indicative of an increased risk of asthma exacerbations (see pg. 20, para. [0249]).
Zhou does not teach the composition comprising at least one strain from the bacterial genus Streptococcus.
Grandi teaches that changes in the bacterial composition of nasal microbiota may alter the host’s susceptibility to several infectious diseases, and a strong and significant decrease in Staphylococcus aureus abundance was detected immediately after the bacterial administration of Streptococcus salivarius 24SMBc and Streptococcus oralis 89a (see Abstract). Grandi teaches that this reduction could be due to a potential ability of the two strains to displace the pathogens or to predominate the unwanted microbial species as previously described for lactic acid bacteria (e.g., Lactobacilli) that exert antiadhesive and antimicrobial effects against S. aureus strains or other opportunistic pathogens (see pg. 1223, col. 2, para. 2). Grandi teaches that the nasal microbiota is a complex microbial community, composed of several different genera of aerobic and anaerobic microorganisms such as Staphylococcus spp., Corynebacterium spp., and Propionibacterium spp. (see pg. 1219, col. 1). Grandi teaches that several studies demonstrated how commensal alpha-hemolytic streptococci could be used to recover the normal nasopharyngeal flora in children with recurrent otitis media, and these microorganisms may not only restore the balance between beneficial commensal bacteria and pathogenic species but may also prevent development of antimicrobial resistance due to the intensive use of antibiotics in the treatment of nasal diseases (see pg. 1219, col. 2, para. 1). Grandi discloses a probiotic product based on the combination of Streptococcus salivarius 24Mbc and Streptococcus oralis 89a, developed for direct nasal administration through a vaporizer for the prophylaxis and treatment of chronic and recurrent infections of the upper airways (see pg. 1219, col. 2, para. 2). Grandi teaches that the reduction of potential harmful bacteria demonstrated in the study is an important feature of the two probiotic streptococcal strains and indicates a promising use for future applications in the clinical field (see pg. 1226, col. 1, para. 1).
It would have been obvious at the time of filing for a person of ordinary skill in the art to have arrived at the claimed invention by combining the teachings of Zhou and Grandi, because both references teach compositions comprising beneficial nasal probiotics that are useful for the prophylaxis and treatment of pathogenic infections of the respiratory system. One would have also recognized that both references teach that beneficial probiotics, such as Corynebacterium and Lactobacillus, have the ability to inhibit and displace disease-causing bacteria, such as Streptococcus pneumoniae and Staphylococcus aureus, and teach that the nasal administration of beneficial probiotics (i.e., Corynebacterium, Dolosigranulum, Lactobacillus, and alpha-hemolytic strains of Streptococcus) can effectively prevent or treat diseases of the respiratory system. Hence, one would have been particularly motivated to provide a composition which combined these desired effects. One would have also recognized that each element (i.e., probiotic strain) could have been combined by known methods, and that in combination, each element merely performs the same function as it does separately (i.e., inhibits and/or displaces pathogenic bacteria). As such, one would have recognized that the results of the combination to have been predictable and there to have been a reasonable expectation of success when applying the combination. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Regarding claim 28, Zhou teaches all the elements of claim 16, as discussed under 35 U.S.C. 102, and the further limitations of the claim are the same as claim 6 above. Hence, the claim is obvious for the same reasons discussed regarding claims 6 and 16.
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhou and Grandi as applied above, and further in view of Harburger, et al. (US Patent No. 12,329,792 B2; effectively filed 05/28/2020; previously cited), hereafter, “Harburger”.
Regarding claim 9, Zhou and Grandi teach compositions comprising beneficial bacteria, such as Corynebacterium, Dolosigranulum, Lactobacillus, and alpha-hemolytic strains of Streptococcus, to prevent and treat respiratory infections by pathogenic bacteria, such as Streptococcus pneumoniae and Staphylococcus aureus, and Zhou teaches that a higher relative abundance of Corynebacterium and Dolosigranulum and a lower relative abundance of the pathogenic bacteria is associated with favorable clinical outcomes in subjects having asthma, as discussed above.
Zhou and Grandi do not explicitly teach wherein the probiotic strains are in a ratio of about 1:0.01:0.01:0.01 to about 1:1:1:1.
Harburger teaches compositions and methods comprising live Corynebacterium and/or
Dolosigranulum pigrum bacteria for the modulation, restoration and/or promotion of the microbiome in the upper respiratory tract of a subject, including the nasal cavity, to promote health (see Abstract). Harburger teaches that probiotic bacteria provide a therapeutic opportunity for addressing microbiome imbalance and disease related conditions, and there is a need for forms of intervention which promote an improved microbiome environment in the upper respiratory tract, in particular the nasal cavity, for the treatment and prevention of conditions in the nasal cavity as well as in systems linked to the upper respiratory tract by a shared mucosal network, such as the lower respiratory tract and central nervous system (see col. 1, lines 21-27). Harburger teaches that lower respiratory tract conditions for treatment or prevention by the administration of the composition includes asthma (see col. 10, lines 52-55). Harburger teaches that the bacteria selected for the composition are used to control, treat, reduce, eliminate, and/or prevent pathogenic colonization by an organism in a subject, and the composition may be administered for delivery to the upper respiratory tract, including the nasal cavity (see col. 4, lines 33-35). Harburger teaches that when administered to a subject, the bacterial population reduces or eliminates colonization in the respiratory tract of pathogenic bacteria, such as Staphylococcus aureus (see col. 6, lines 45-50). Harburger teaches that the composition comprises a bacterial population of up to 4 or more strains comprising at least one strain of Corynebacterium and at least one strain of Dolosigranulum, and such strains may be present in equal amounts or varied amounts (see col. 6, lines 9-15, 29-33).
Hence, Harburger’s disclosure is closely related to solving the same problem as Zhou using a particularly similar means (i.e., administering Corynebacterium and Dolosigranulum to inhibit pathogens of the respiratory system to treat and prevent lower respiratory conditions, such as asthma). Further, Harburger’s disclosure of providing up to 4 or more strains “in equal amounts” is equivalent to the claimed limitation of providing the strains in a ratio of “about 1:1:1:1”. In view of the instant specification, the term “about” means a value falling within a range that is ± 10% of the stated value (see instant specification at pg. 8, para. [0030]). Hence, Harburger’s disclosure of providing the strains “in equal amounts” is within the claimed range, and the ratio of “1:1:1:1” would have been prima facie obvious in view of Harburger.
Therefore, it would have been obvious at the time of filing for a person of ordinary skill in the art to have arrived at the claimed invention by combining the teachings of Zhou, Grandi and Harburger because each reference teaches compositions comprising beneficial nasal probiotics that are useful for the prophylaxis and treatment of pathogenic infections of the respiratory system. One would have also recognized that each reference teaches that beneficial probiotics, such as Corynebacterium, Dolosigranulum, Lactobacillus, and alpha-hemolytic strains of Streptococcus, have the ability to inhibit and displace disease-causing bacteria, such as Streptococcus pneumoniae and Staphylococcus aureus, and further teach that the nasal administration of such probiotics can effectively prevent or treat diseases of the respiratory system, such as asthma. Hence, one would have been particularly motivated to have provided a composition which combined these desired effects. One would have also recognized that each element (i.e., probiotic strain) could have been combined by known methods, and that in combination, each element merely performs the same function as it does separately (i.e., inhibits and/or displaces pathogenic bacteria). As such, one would have recognized that the results of the combination to have been predictable and there to have been a reasonable expectation of success when applying the combination. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Response to Arguments
Regarding the rejection under 35 U.S.C. 101, Applicant argues that amended claim 1 is directed to a combination of a selected bacterial strain or consortium, as well as one or more pharmaceutically acceptable carriers, which are together in the form of a pharmaceutical composition. Accordingly, the claims are directed to a manufactured pharmaceutical formulation rather than a naturally occurring product and therefore are not directed to a judicial exception. Furthermore, claim 1 recites strains that exhibit activity that inhibits Streptococcus pneumoniae in the respiratory system of a subject. This functional feature further distinguishes the claimed pharmaceutical formulation from naturally occurring bacteria existing in their natural environment.
Applicant’s arguments have been fully considered but they are not persuasive.
First, the limitation of a “pharmaceutically acceptable carrier” does not result in a markedly different characteristic, as discussed in the rejection. This broad recitation includes compounds, such as water, which are already present with the bacterium in its naturally-occurring environment. Therefore, the composition as a whole is directed to a natural product without significantly more. The process which the composition as whole is arrived at (i.e., “manufactured”) is not a consideration for determining the eligibility of a product claim, particularly where it does not imply any further structure, and this feature is also not recited in the claim.
Furthermore, Applicant fails to discuss how the added functional limitations of the claims distinguish the bacteria from their naturally occurring counterparts. MPEP 2106.04(c) states, if the nature-based product limitation is naturally occurring, there is no need to perform the markedly different characteristics analysis because the limitation is by definition directed to a naturally occurring product and thus falls under the product of nature exception. However, if the nature-based product limitation is not naturally occurring, for example due to some human intervention, then the markedly different characteristics analysis must be performed to determine whether the claimed product limitation is a product of nature exception.
In the instant case, the breadth of the claim clearly captures natural products (i.e., “a strain from the bacterial genus Corynebacterium) and is not limited to a “consortium”. It should be noted that even a “consortium” includes natural products (i.e., the respiratory/nasal microbiome). Applicant argument fails to show how (1) the nature-based products are limited to those that are not naturally occurring and further (2) how these non-naturally occurring products have markedly different characteristics from the strains from which they were derived. Merely isolating a bacterium from nature and reciting its natural properties is insufficient to overcome the judicial exception, even if these properties were not previously known.
Regarding the rejections under 35 U.S.C. 102, Applicant argues that amended claim 1 recites “… the strain or at least one of the strains from the bacterial genus Corynebacterium exhibits activity that inhibits Streptococcus pneumoniae in the respiratory system of a subject”. The recited feature of the specific strain of Corynebacterium exhibiting activity that inhibits Streptococcus pneumoniae in the respiratory system of a subject is neither disclosed nor taught by Zhou. Whilst Zhou may generally describe Corynebacterium species as potentially beneficial commensals, and potentially their administration, Zhou does not disclose selecting a Corynebacterium strain that exhibits activity that inhibits Streptococcus pneumoniae in the respiratory system of a subject.
Applicant’s arguments have been fully considered but they are not persuasive.
First, none of the previously rejected claims recite a “specific strain” of Corynebacterium. Only newly added claims 41 and 51 recite specific strains, which are not included in the rejection under 102. Claim 1, in particular, is directed to any species of Corynebacterium.
Second, Zhou does more than merely “generally describe” this genus of bacterium as “potentially beneficial commensals”. Zhou literally states that “Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products that may prevent nasal colonization with Streptococcus” and teaches the administering of Corynebacterium to treat respiratory infections caused by Streptococcus pneumoniae, as discussed in the rejections. Therefore, this further limitation of the claim is directed to an inherent property of the bacterium, as discussed in the present rejection.
Applicant further argues that Zhou contains no teaching that anti-pneumococcal activity varies from strain to strain within the same Corynebacterium species. Whereas Applicant's specification demonstrates that inhibition of Streptococcus pneumoniae is not a generalized property of Corynebacterium genus, nor even of a particular Corynebacterium species. Instead, the Examples demonstrate that this activity is strain dependent. For instance, Applicant's specification reports that C. accolens strain 05-122, C. tuberculostearicum strain 05-144, and C. coyleae strain 05-104 inhibited S. pneumoniae, whereas C. accolens strain 05-161, C. tuberculostearicum strain 05-150, and C. propinquum strain 05-124 did not exhibit such inhibitory activity.
Applicant’s arguments have been fully considered but they are not persuasive.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., C. accolens strain 05-122, C. tuberculostearicum strain 05-144, and C. coyleae strain 05-104) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In the instant case, only newly added claims 41 and 51 recite 05-122, 05-144 and 05-104. Applicant’s arguments, as they apply to these claims, are moot because they are not included in this rejection.
Furthermore, whether or not Zhou proves or demonstrates that any Corynebacterium strain has anti-pneumococcal activity is irrelevant under 35 U.S.C. 102. Per MPEP 2121, a prior art reference provides an enabling disclosure and thus anticipates a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; "proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation." Impax Labs. Inc. v. Aventis Pharm. Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006) (citing Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1326, 75 USPQ2d 1297, 1302 (Fed. Cir. 2005). In the instant case, the claims rejected under 35 U.S.C. 102 recite the same genus and/or species of bacterium as Zhou, which anticipates the claims.
Applicant further argues that Claim 16 has been amended in a similar manner (e.g., to recite " ... inhibiting Streptococcus pneumoniae in the respiratory system of a subject in need of treatment ... "). For substantially similar reasons as discussed above for amended Claim 1, Zhou does not disclose the presently claimed method of amended Claim 16.
Applicant’s arguments have been fully considered but they are not persuasive.
While the examiner acknowledges that the amendment now requires the “subject in need” to be one having Streptococcus pneumoniae in their respiratory system, the functional limitation of “inhibiting” is directed to an inherent property, as discussed above and in the present rejection.
Regarding the rejections under 35 U.S.C. 103, Applicant argues that Zhou generally describes Corynebacterium as a beneficial respiratory commensal and discusses respiratory microbiomes. De Grandi describes Streptococcus strains for upper respiratory applications. Harburger describes respiratory microbiome restoration involving Corynebacterium and Dolosigranulum. However, none of these references teaches or suggests selecting a Corynebacterium strain for the reason that it exhibits activity of selectively inhibiting Streptococcus pneumoniae in the respiratory system of a subject, as now recited in the amended claims.
Applicants' specification demonstrates that inhibition of Streptococcus pneumoniae is a strain-dependent phenotype, rather than an inherent property of Corynebacterium genus generally. Applicant again argues that the specification reports that C. accolens strain 05-122, C. tuberculostearicum strain 05-144, and C. coyleae strain 05-104 inhibit Streptococcus pneumoniae, whereas other strains of those same species, including C. accolens strain 05-161, C. tuberculostearicum strain 05-150 do not exhibit such inhibitory activity. Thus, the recited functional feature cannot be satisfied merely by selecting any Corynebacterium strain, as purported in the Office Action.
Applicant’s arguments have been fully considered but they are not persuasive.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., C. accolens strain 05-122, C. tuberculostearicum strain 05-144, and C. coyleae strain 05-104) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In the instant case, these strains are only recited in newly added claims 41 and 51, which are not included in the rejection.
Applicant’s examples only compare the effects of six strains on the growth of two particular strains of S. pneumoniae in an in vitro culture, wherein half the strains had the effect of inhibiting growth during a 24 hour period. This evidence is insufficient to demonstrate that these results were surprising or unpredictable over the expectations set forth in the prior art.
Harburger, for example, specifically teaches procedures for selecting Corynebacterium and Dolosigranulum strains for the inhibition of S. pneumoniae using growth/inhibition assays, as well as mouse models (see col. 59, line 61 to col. 60, line 53). Therefore, strains having this activity could be readily acquired using the same methods known in the prior art.
As discussed in the rejections, the prior art of Zhou specifically teaches reducing the relative abundance of S. pneumoniae by the administering of Corynebacterium, and teaches that Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products to prevent colonization by Streptococcus. Zhou also teaches that, via competitive colonization, Corynebacterium and Dolosigranulum collectively help the nasal microbiome reach a state of equilibrium, which is more resistant to further colonization with pathogenic bacteria (see pg. 23, para. [0274]). Therefore, one would appreciate that there are various ways these probiotics contribute to inhibiting pathogenic bacteria in the respiratory system, particularly when administered in combination, and their colonization would be expected to have an inhibitory effect, i.e., via competitive exclusion of Streptococcus pneumoniae.
Applicant further argues that Applicant's experimental results demonstrate that anti-pneumococcal activity is not predictable across Corynebacterium strains. Because the specification identifies both inhibitory and non-inhibitory strains within the same Corynebacterium species, one of ordinary skill in the art would not have reasonably expected that selecting an arbitrary Corynebacterium strain for inclusion in a probiotic consortium would necessarily produce inhibition of Streptococcus pneumoniae. Rather, Applicant discovered that this therapeutically relevant activity is a property of selected strains, not of Corynebacterium generally. Accordingly, the cited references do not provide a reasonable expectation of arriving at the presently claimed pharmaceutical formulations or methods.
Applicant’s arguments have been fully considered but they are not persuasive.
Applicant’s examples only compare the effects of six strains on the growth of two particular strains of S. pneumoniae in an in vitro culture, wherein half the strains had the effect of inhibiting growth during a 24 hour period. This evidence is insufficient to demonstrate that these results were surprising or unpredictable over the expectations and guidance provided in the prior art.
Harburger, for example, specifically teaches procedures for selecting Corynebacterium and Dolosigranulum strains for the inhibition of S. pneumoniae using growth/inhibition assays, as well as mouse models (see col. 59, line 61 to col. 60, line 53). Therefore, strains having this activity could be readily acquired using the same methods known in the prior art. Growth-inhibition assays are an extremely common and straightforward tool for assessing antimicrobial activity. Hence, even if some strains did not have all of the desired activity against a particular strain of S. pneumoniae, this activity could be easily verified by an ordinary artisan.
Furthermore, Zhou specifically teaches reducing the relative abundance of S. pneumoniae by the administering of Corynebacterium, and teaches that Corynebacterium and Dolosigranulum can inhibit the growth of Streptococcus by releasing antibacterial products. Zhou also suggests that via competitive colonization, Corynebacterium and Dolosigranulum collectively help the nasal microbiome reach a state of equilibrium, which is more resistant to further colonization with pathogenic bacteria (see pg. 23, para. [0274]). Therefore, one would appreciate that there are various ways these probiotics contribute to inhibiting pathogenic bacteria, particularly when administered in combination, and recolonization of the airways with such probiotics would be expected to have a prohibitory effect via competitive exclusion of the pathogens.
Regarding the newly added claims, Applicant argues that claims 41-60 are patentable for at least the reasons above.
Applicant’s arguments have been fully considered but they are not persuasive for the same reasons set forth above, as well as the reasons set forth in the new grounds of rejections under 35 U.S.C. 102, 35 U.S.C. 112(a) and 35 U.S.C. 101.
It should be noted that claims 41 and 51 are free of any rejection under 35 U.S.C. 102 or 103, based solely on the recited strain numbers, as discussed further below. However, these claims are not directed to patentable subject matter for the reasons discussed under 35 U.S.C. 101 and 35 U.S.C. 112(a).
Conclusion
No claims are allowed.
Claims 41 and 51 recite the limitation of “wherein the strain or the at last one strain from bacterial genus Corynebacterium comprises C. tuberculostearicum strain 05-144, C. coyleae strain 05-104, C. accolens strain 05-122, or a combination thereof”. These bacterial strain designation numbers do not appear in the prior art of record, and there is insufficient evidence for the examiner to determine the existence of any prior art equivalent(s). Therefore, in the absence of any evidence to the contrary, these claims are free of the prior art. However, these claims also fail to meet the enablement requirement, as discussed under 35 U.S.C. 112(a). Claim 41 is also directed to patent ineligible subject matter, as discussed under 35 U.S.C. 101.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/DENNIS IGNATIUS ARMATO JR/Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651
