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 . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Priority
The instant application is a 371 of PCT/JP2022/046989 filed on 12/21/2022 and claims foreign priority to JP2021-208198 filed on 12/22/2021. The certified copy of the foreign priority application filed on 06/14/2024 is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/04/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of the Claims
The preliminary claim amendments filed on 06/14/2024 is acknowledged. Claims 1-12 are amended.
Accordingly, claims 1-12 are pending and being examined on the merits herein.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for reducing risk of developing a secondary infectious disease after a virus infection, does not reasonably provide enablement for preventing a secondary infectious disease after a virus infection. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Formal, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) The breadth of the claims,
2) The nature of the invention,
3) The state of the prior art,
4) The level of one of ordinary skill,
5) The level of predictability in the art,
6) The amount of direction provided by the inventor,
7) The existence of working examples, and
8) The quantity of experimentation necessary
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention, the breadth of the claims, and relative skill level
The invention relates to a method for preventing a secondary infectious disease after a virus infection, or for reducing risk of developing a secondary infectious disease after a virus infection, the method comprising: administering a composition comprising an exopolysaccharide of lactic acid bacteria to a subject in need of preventing a secondary infectious disease after a virus infection, or of reducing risk of developing a secondary infectious disease after a virus infection.
The claims are broad in that they encompass the prevention of secondary infectious disease after a virus infection in a subject in need of preventing a secondary infectious disease after a virus infection.
In the absence of an explicit definition in Applicant’s specification, the claims are given their broadest reasonable interpretation (See MPEP 2111). Institute for International Medical Education (IIME, reference included with PTO-892), defines “prevention” as promoting health, preserving health, and to restore health when it is impaired, and to minimize suffering and distress (see page 16, “Prevention”). IIME further states that “Primary prevention refers to the protection of health by personal and community wide effects, such as preserving good nutritional status, physical fitness, and emotional well-being, immunizing against infectious diseases, and making the environment safe. Secondary prevention can be defined as the measures available to individuals and populations for the early detection and prompt and effective intervention to correct departures from good health. Tertiary prevention consists of the measures available to reduce or eliminate long-term”.
Therefore, in order to give the broadest reasonable interpretation to the claims, “prevention” or "prevent" are thus interpreted to mean that the onset of a condition never occurs and the patient’s health is protected and preserved.
The relative skill of those in the art is high, that of an MD or PHD, someone with experience in the recited conditions/diseases.
The amount of direction or guidance provided and the presence or absence of working examples
Applicant discloses that respiratory viruses promote bacterial adhesion to epithelial cells through adhesion molecules induced by viruses (paragraph 0063 page 22), and further demonstrates in the Examples (paragraph 0063-0066 pages 22-23) and in FIGS. 2-3 that expression of CEACAM-1 mRNA and the numbers of adhered bacteria in virus-infected A549 was decreased after EPS treatment (exopolysaccharide from OLL1073R-1 paragraph 0054 page 19).
However, the instant disclosure does not identify a method that could be used by one of ordinary skill in the art to determine that a subject would have predictably developed the secondary infectious disease after virus infection without the claimed methods in order to establish that the condition was prevented.
The described example suggests that the EPS from OLL1073R-1 can be used to reduce the adherence of bacteria such as pathogens of secondary infectious diseases and therefore reduce the risk of developing a secondary infectious disease after a virus infection. However, the examples do not demonstrate prevention of secondary infectious disease after virus infection or a predictable method to identify patients who would have developed this condition.
The state and predictability of the art
There are no art recognized methods that could be used to establish that secondary infectious disease after virus infection was prevented using the therapeutic treatment or to identify patients who would predictably develop secondary infectious disease after virus infection in order to predictably identify that prevention was achieved using therapeutic approaches. Rather, the art indicates that preventing secondary infectious disease after virus infection was not predictable.
McCullers (in PTO-892) discusses the prevention of secondary bacterial infection (SBI) associated with influenza and other respiratory virus infections (Abstract).
McCullers discloses that prevention of SBI by intervention prior to its development would be preferred. However, most cases of influenza are not brought to medical attention or are managed in outpatient settings (second paragraph page 2). Furthermore, McCullers discloses that antiviral treatment is currently recommended by the Centers for Disease Control (CDC) and the Infectious Diseases Society of America (IDSA) at presentation in persons with certain high-risk medical conditions, but for healthy persons only after hospitalization is required or complications develop (second paragraph page 2). McCullers discloses that since the risk factors for development of SBI following influenza are not known, and less than half of persons who develop secondary bacterial pneumonia requiring hospitalization have medical conditions placing them at high risk for hospitalization from influenza, this strategy is likely to miss most opportunities for preventing SBI with antiviral medications (second paragraph page 2). McCullers also discloses that role of respiratory viruses in the pathogenesis of SBI remains unclear (last paragraph page 3).
The teachings of McCullers demonstrate that there is no method that exists to predictably determine how secondary bacterial infections associated with influenza are developed, and further that there is no predictable method to prevent this condition.
The quantity of experimentation necessary
Because of the known unpredictability of the art, and in the absence of a predictable method to identify patients who would develop secondary infectious disease after virus infection without treatment, one of ordinary skilled in the art would not be able to predictably use the claimed composition to prevent secondary infectious disease after virus infection. Furthermore, the quantity of experimentation would be undue because a method to identify a patient who would predictably get this condition in order to establish that the claimed method results in prevention does not exist.
Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Claims 5 and 12 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.
Claims 5 and 12 recite that the administration of a composition comprising exopolysaccharides from the Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1 (FERM BP-10741). Therefore, it is apparent that exopolysaccharides from the Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1 (FERM BP-10741) is required to practice the claimed invention. As such, the OLL1073R-1 biological material must be known and readily available or obtainable by a repeatable method set forth in the specification, or otherwise known and readily available to the public. If it is not so obtainable or available, the requirements of 35 USC 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, may be satisfied by a deposit of the OLL1073R-1.
Applicant has disclosed that the OLL1073R-1 (referred to as bulgaricus R-1 strain) was deposited at an international deposition at the independent administrative agency, National Institute of Technology and Evaluation, International Patent Organism Depositary (IPOD, NITE, Room 120, 2-5-8 Kazusakmadzhi, Kisarazu, Chiba, Japan) under the terms of the Budapest Treaty. (Depositor, Meiji Co., Ltd.; date of deposition, Nov. 29, 2006; accession number, FERM BP-10741) (paragraphs 0020-0021 pages 9-10). However, there is no indication in the specification as to the public availability or if restrictions on availability will be lifted.
If a deposit is made under the provisions of the Budapest Treaty, filing of an affidavit or declaration by applicant or assignees or a statement by an attorney of record who has authority and control over the conditions of deposit over his or her signature and registration number stating that the deposit has been accepted by an International Depository Authority under the provisions of the Budapest Treaty and that all restrictions upon public access to the deposited material will be irrevocably removed upon the grant of a patent on this application. This requirement is necessary when deposits are made under the provisions of the Budapest Treaty as the Treaty leaves this specific matter to the discretion of each State.
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) 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Bauer et al. (WO2020182970A1 in IDS filed 09/04/2024) in view of Nagai et al. (International Immunopharmacology, 2011 in IDS filed 09/04/2024).
Bauer discloses novel stable bacterial extract preparations and pharmaceutical formulation containing these novel stabilized bacterial extracts, as well as novel routes of administration and delivery devices for treating and/or preventing acute and chronic immunological disorders resulting from infections and/or inflammation and/or neoplasms and/or dysbiosis (Abstract).
Bauer discloses that constant exposure of the mucosal surfaces like airways and lungs to inhaled viruses, bacteria and toxins presents a challenge to the immune system and that the situation becomes even worse when the host is exposed to viral infection and subsequently is superinfected by microbes leading to an increased mortality rate (paragraph 006). Accordingly, Bauer discloses that bacterial secondary infections following viral infections with influenza (H1N1 and the like), human rhinovirus (HRV), rhinosyncitial virus (RV), coronavirus (CoV, SARS-CoV, MERS-CoV, COVID-19 and the like) are a pressing problem facing respiratory medicine (paragraph 006).
Bauer discloses in one embodiment, the stable bacterial extract formulation is prepared from one or more bacterial species chosen from Lactobacillus bacterial strains such as Lactobacillus bulgaricus, Lactobacillus fermentum, and others (paragraph 0064). Bauer discloses that the Lactobacillus bacterial extract can be used to treat and/or prevent several respiratory tract infections including, influenza, human rhinovirus, pneumonia, obstructive pulmonary disease, secondary infections, and others (paragraph 00117). Bauer discloses that the lactobacillus bacterial strains are also particularly useful for treating and/or preventing rhinitis and/or allergic rhinitis, which is trivially called common cold symptoms with stuffy nose or runny nose (paragraph 00122).
Bauer discloses that their bacterial extract preparations involve a filtration step to remove insoluble particles as well as nucleic acids present (paragraph 0081). However, Bauer discloses that saccharide components, including monosaccharides, disaccharides, as well as larger saccharides such as linear and branched polysaccharides, and particularly the lipopolysaccharide (LPS) components, may be preserved by the filtration (paragraph 0081). Bauer discloses that it was previously thought that saccharide components, including potentially toxic LPS components should be removed from bacterial extracts for safety reasons, however Applicant shows that saccharides components, including LPS, may be safely retained as these components in fact provide additional antigens to the extracts and thus improve the therapeutic efficacy (paragraph 0081). Bauer discloses that the bacterial extracts comprise more than 0.1 mg/mL (100 ug/mL) of polysaccharides (paragraph 0086).
Bauer demonstrates in Example 4 (pages 76-78) the prophylactic and curative efficacy of a bacterial extract containing bacterial extracts from 21 strain lysates in a superinfection animal model of sub-lethal bacterial infection following primo influenza infection.
Bauer illustrates in FIG. 3 and in Table 23 (page 77) that the animal model comprises of initially administering the bacterial extract compositions via oral or intranasal administration in defined intervals for several days before infecting the mice with 100 PFU influenza A/PR/8/34 (H1N1). After viral infection, the mice were analyzed for the viral load of the influenza and then intranasally administrated streptococcus pneumonia 7 days after influenza infection and morbidity/mortality was measured.
Bauer demonstrates in FIGS. 4-6 that their bacterial extract treatment protected mice against morbidity and mortality in the initial viral - secondary bacterial superinfection model (lines 1-5 page 78).
Bauer further demonstrates in Example 2.2 and 2.5 that one of the tested bacterial extract strains was Lactobacillus fermentum (extract 20 OMB314B) and further demonstrates intranasal and inhalation formulations of this extract (page 74 lines 16-25 and page 75 lines 13-20). Bauer also demonstrates that the produced Lactobacillus fermentum extract contained sugars in Table 5 (pages 46-47).
While Bauer teaches bacterial extracts that can be derived from Lactobacillus species and can contain polysaccharides as well as a method for the prophylactic administration of their bacterial extracts against secondary bacterial infection such as streptococcus pneumonia following influenza infection, Bauer does not teach that the polysaccharides in their bacterial extracts are exopolysaccharides.
Nagai discloses the oral administration of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 and its exopolysaccharides (EPS) to treat influenza virus infection in mice (Abstract).
Nagai discloses that Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) OLL1073R-1 originated from traditional Bulgarian yogurt and was reported to produce immunostimulatory exopolysaccharide (EPS) (second paragraph right column page 2246). Nagai discloses that they previously investigated whether the intake of the yogurt fermented with this strain enhanced immune functions of elderly and reduced the risk of respiratory infections in two independent cohort studies and that during the intake period, the risk of catching the common cold in the yogurt intake group was significantly lower than the milk intake group, and the yogurt intake group found to augment NK cell activity in the subjects who had lower NK cell activity (second paragraph right column page 2246).
Nagai demonstrates in FIG. 1-2 (page 2248) the effects of the yogurt and EPS on the proliferation of H1N1 influenza virus in lung of mice. Nagai discloses that the BALB/c mice were administered orally with water, yogurt or EPS from 21 days before influenza infection to 3 days post infection.
Nagai demonstrates that the survival periods were prolonged in both yogurt- and EPS-treated groups compared to the control water-treated group. Moreover, in these groups, Nagai observed significant decrease of influenza virus titer and significant increase of anti-influenza virus antibodies (IgA, IgG1) in the bronchoalveolar lavage fluid at 4 days post infection NK cell activity of splenocytes in both groups was also increased significantly (Abstract). Nagai concludes that the yogurt fermented with OLL1073R-1 exerted anti-influenza virus effects in mice by its immunopotentiating activity, and suggested that an EPS produced by OLL1073R-1 was one of active ingredients (Abstract).
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the bacterial extract preparation disclosed in Bauer by further including the Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 species and its EPS component as disclosed in Nagai to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because both Bauer and Nagai teach the treatment of the same H1N1 influenza infection by administering their respective compositions which comprise of a Lactobacillus species. Furthermore, Bauer discloses retaining the polysaccharides present in their bacterial extracts to provide improved therapeutic efficacy, and Nagai demonstrates that the EPS in OLL1073R-1 was one of the active ingredients.
In regards to instant claims 2 and 6, it would have also been prima facie obvious before the effective filing date of the claimed invention to have modified the treatment method as disclosed by the combined teachings of Bauer and Nagai described above by treating human rhinovirus as disclosed in Bauer to reduce the risk of catching the common cold in elderly patients as disclosed in Nagai to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because Bauer discloses the use of their bacterial extracts for treating human rhinovirus and further discloses that the Lactobacillus bacterial strains are particularly useful for treating and/or preventing rhinitis which is trivially called common cold symptoms with stuffy nose or runny nose. Furthermore, Nagai discloses that the yogurt containing L. bulgaricus OLL1073R-1 given to elderly people was able to significantly lower the risk of catching the common cold.
In regards to instant claims 7-12, even though the combined teachings of Bauer and Nagai described above do not teach suppressing increase of expression of CAECAM-1, this function would flow naturally from the following the teachings of the prior art because as shown in the Examples (paragraph 0063-0066 pages 22-23) and in FIG. 2 of the instant specification, the expression of CEACAM-1 mRNA in H1N1 influenza virus-infected A549 cells was decreased after EPS treatment (exopolysaccharide from OLL1073R-1 paragraph 0054 page 19) at dosages of 100, 200, and 400 ug/mL (paragraph 0061 page 21), and the combined references described above provide guidance of treating the same H1N1 influenza infection by administering a composition comprising the same EPS from OLL1073R-1 within the same effective amounts (100 ug/mL or greater).
MPEP 2145 II states that “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter.m 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed that an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) ("The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.").”
Conclusion
No claim is found allowable.
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/D.H.C./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner
Art Unit 1693
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