Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of Claims
Claims 25-34 are pending.
Claim Rejections - 35 USC § 112 (a)
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 25-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a specific immune disease such as atopic dermatitis and COPD, does not reasonably provide enablement for treating each and every immune disease and metabolic disease with the claimed Lactobacillus plantarum derived extracellular vesicles. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112 (a) have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner's position that one skilled in the art could not practice the invention without undue experimentation.
(1) The nature of the invention and (2) The breadth of the claims:
All claims are drawn to a method for treating all types of immune diseases and metabolic disease. The claims are very broad since immune diseases and metabolic disease encompass: one or more gastrointestinal diseases selected from the group consisting of gastritis, peptic ulcers, celiac disease, and inflammatory bowel disease; one or more oral diseases selected from the group consisting of gingivitis, periodontitis, and caries; one or more female vaginal diseases selected from the group consisting of candida vaginitis, atrophic vaginitis, bacterial vaginitis or vaginosis, and trichomonas vaginitis; one or more liver-biliary-pancreatic diseases selected from the group consisting of non-alcoholic steatohepatitis (NASH), alcoholic steatohepatitis, liver cirrhosis, cholangitis, cholecystitis, and pancreatitis; one or more lung diseases selected from the group consisting of chronic obstructive pulmonary disease, chronic interstitial pneumonitis, emphysema, bronchopulmonary dysplasia, and idiopathic pulmonary fibrosis; one or more cardiovascular diseases selected from the group consisting of hyperinsulinemia, dyslipidemia, arrhythmia, atherosclerosis, angina, metabolic syndrome, myocardial infarction, stroke, and cardiomyopathy; one or more renal diseases selected from the group consisting of glomerulonephritis, and chronic nephropathy; one or more musculoskeletal diseases selected from the group consisting of atony, muscular atrophy, muscular dystrophy, myasthenia gravis, cachexia, gout, sarcopenia, osteoporosis, Paget's disease, rheumatoid arthritis, and osteoarthritis; and one or more neurological diseases selected from the group consisting of mild cognitive impairment, dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), Batten disease, Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), myoclonic epilepsy with ragged-red fibers (MERRF) syndrome, neurogenic weakness with ataxia and retinitis pigmentosa (NARP) syndrome, Leigh syndrome (LS), mitochondrial recessive ataxia syndrome (MIRAS), dementia with Lewy bodies (DLB), multi-infarct dementia (MID), frontotemporal lobar degeneration (FTLD), Pick's disease, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), age-related macular degeneration (AMD), dysosmia, deafness, and diabetic retinopathy. They all have different etiology and pathophysiology. In addition, the immune disease encompasses immune deficiency-related diseases such as AIDS as well as autoimmune diseases.
(3) The state of the prior art
There are no known agents of similar structure or compositions which have been demonstrated to treat all types of metabolic disorders and immune diseases including those requiring immuno-stimulation such as AIDS as well as those immune-suppression such as autoimmune diseases.
(4) The relative skill of those in the art
Generally, the relative skill of those in the art of pharmaceuticals and pharmacology is high. Applicant has not provided any competent evidence or disclosed tests that are highly predictive for the pharmaceutical use of the instant composition for accomplishing the desired result of the claimed invention without undue experimentation. Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved”. See In re Fischer, 427 F.2d 833, 839, 166 USPQ 10, 24(CCPA 1970).
(5) The predictability or unpredictability of the art
First of all, the treatment of “immune diseases” generally would be an unprecedented feat. For a compound or genus to be effective against “immune diseases” generally is contrary to medical science. There are dozens of such diseases, which have fundamentally different mechanisms and different underlying causes. The “immune diseases” also include both autoimmune diseases and immunodeficiency diseases such as AIDS. Known autoimmune disorders include multiple sclerosis, autoimmune uveitis, rheumatoid arthritis, Addison's disease, thyroiditis, atrophic gastritis, myasthenia gravis, idiopathic thrombocytopenic purpura, hemolytic anemia, systemic lupus erythematosus, primary biliary cirrhosis, Wegener's granulomatosis, polyarteritisnodosa, erythema nodosum leprosum, autoimmune uveitis, Guillain-Barré syndrome (GBS), allergic encephalomyelitis, acute necrotizing hemorrhagic encephalopathy, idiopathic bilateral progressive sensorineural hearing loss, aplastic anemia, pure red cell anemia, polychondritis, scleroderma, Stevens-Johnson syndrome, idiopathic sprue, lichen planus, Crohn's disease, Graves ophthalmopathy, sarcoidosis, primary biliary cirrhosis, type I diabetes, autoimmune optic neuritis, uveitis posterior, or interstitial lung fibrosis, alopecia, Sjogren's Syndrome, Goodpasture Syndrome, Myasthenia Gravis, inflammatory bowel disease and many more. There are both chronic and acute “autoimmune diseases”, most of which lack satisfactory treatment. The intractability of these disorders is clear evidence that the skill level in this art is low relative to the difficulty of the task. Under such circumstances, it is proper for the PTO to require evidence that such an unprecedented feat has actually been accomplished. The failure of skilled scientists to achieve a goal is substantial evidence that achieving such a goal is beyond the skill of practitioners in that art, Genentech vs. Novo Nordisk, 42 USPQ2nd 1001, 1006.
In fact, immune diseases are disorders in which the body's immune system reacts against some of its own tissue and produces antibodies to attack itself. Autoimmune disorders are classified into two types, organ-specific (directed mainly at one organ) and non-organ-specific (widely spread throughout the body). Examples of organ-specific autoimmune disorders are insulin-dependent diabetes (Type I) which affects the pancreas, Hashimoto's thyroiditis and Graves' disease which affects the thyroid gland, pernicious anemia which affects the stomach, Addison's disease which affects the adrenal glands, and chronic active hepatitis which affects the liver. Examples of non-organ-specific autoimmune disorders are rheumatoid arthritis, multiple sclerosis, lupus and myasthenia gravis. Scientists believe multiple factors such as environmental toxins, heredity, viruses, and certain drugs may play a role in causing an autoimmune disease. Most autoimmune diseases cannot yet be treated directly, but are treated according to symptoms associated with the condition. As stated above, autoimmune diseases are caused by various factors such as environmental toxins, heredity, viruses, and certain drugs, thus administrating the claimed compound treat all types of chronic pulmonary diseases, especially the diseases caused by genetic defect or virus infection. Therefore, treatment of all types of autoimmune diseases with different etiology is highly unpredictable to one skilled in the art at the time of the invention was made.
Also, AIDS, which is a disease of the human immune system caused by the human immunodeficiency virus (HIV), progressively reduces the effectiveness of the immune system, thus it would not be treated by immunosuppression and need antiviral treatment.
In addition, enablement for the scope of “metabolic disorders” generally is not present. For a compound or genus to be effective against “metabolic disorders” generally is contrary to medical science. “Metabolic disorders” are conditions that affect the body's ability to process and use nutrients and energy. They can result from various factors, including genetic mutations, nutritional deficiencies, and organ dysfunction. There is no common mechanism by which all, or even most, “metabolic diseases” arise. Therefore, the treatment of all types of “metabolic disorders” with different etiology is highly unpredictable to one skilled in the art.
Since no compound or agent has shown clinical efficacy against all immune diseases and metabolic diseases, thus no in vivo or in vitro assay could be validated for the identification of such a general agent. Applicants' specification logically must lack such assay data.
(6) The amount of direction or guidance presented or (7) The presence or absence of working examples
Applicants disclosed some effects of the claimed EV on death of skin epithelial cells by pathogenic bacteria Staphylococcus aureus-derived vesicles, a colitis mouse model induced by orally administering an abnormal metabolite dextran, AMPK, and inflammatory mediators ( eamples 3-7). However, there is no demonstrated correlation that the tests and results apply to all types of immune diseases and metabolic disease embraced by the instant claims. Also, in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy.
In addition, the specification provides no direction or guidance for determining the particular administration regimens (e.g., dosages, timing, administration routes, etc.) necessary to treat all of the various immune diseases or disorders, particularly in humans. The direction concerning treating diseases and disorders is found in the specification, which merely describes well known methods of administering therapeutic agents. How is the skilled physician to know what dose to use for each of these pathologically different disorders? There are no guidelines for determining the doses needed to treat, for example, pectic ulcers vs. Alzheimer’s disease vs. atopic dermatitis vs. stroke vs. diabetes. Are the identical doses to be used for treating these unrelated disorders?
Thus, the specification fails to provide sufficient information allowing the skilled artisan to practice the invention commensurate in scope with these claims without undue experimentation.
(8) The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept the assertion that the instantly claimed composition could be predictably used as a treatment of all types of immune diseases and metabolic diseases as inferred in the claims and contemplated by the specification. Accordingly, the instant claims do not comply with the enablement requirement of 35 U.S.C. § 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and ‘patent protection’ is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable” (42 USPQ 2d 1001, Fed. Circuit 1997).
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.
Claims 25-31 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by US 2018/0055894.
US 2018/0055894 teaches a method for preventing or treating an inflammatory disease, which comprises administering a composition comprising lactic acid bacteria-derived extracellular vesicles (EV) as active ingredients to a subject wherein the lactic acid bacteria is Lactobacillus plantarum ([0031] and claims 40 and 43-44).
US 2018/0055894 further teaches that the inflammatory disease includes atopic dermatitis, chronic rhinitis, chronic rhinosinusitis, asthma, chronic obstructive pulmonary disease (COPD), and sepsis (immune diseases) (claim 44). Chronic obstructive pulmonary disease (COPD) is one of lung disease recited in claim 26.
US 2018/0055894 specifically disclose that the EVs isolated by the method of the present invention may have an average diameter of 10 to 300 nm, and preferably 10 to 200 nm ([0020] and [0091]).
US 2018/0055894 teaches that the EVs may be isolated from a culture medium of lactic acid bacteria or food fermented with the lactic acid bacteria ([0021] and [0089]).
US 2018/0055894 teaches that the EVs are naturally or artificially secreted from lactic acid bacteria ([0022] and [0089]).
US 2018/0055894 discloses that the composition is a health functional food or a pharmaceutical composition ([0013] and [0015]).
As such, the instant claims are anticipated by US 2018/0055894.
Claims 32-33 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by KR 20190002079 (cited IDS filed on 11/30/2025; English translation attached).
KR 20190002079 teaches the use of a composition comprising an extracellular vesicle derived from a lactic acid bacterium as an active ingredient for anti-aging wherein the lactic acid bacteria is Lactobacillus plantarum and the extracellular vesicle can be an exosome-like vesicle having a diameter of 20 to 200 nm (abstract and claims 1-4). KR 20190002079 discloses that the term " anti-aging " means an application for preventing, delaying, and / or improving the aging phenomena caused by internal factors including genetic factors and external factors including ultraviolet rays and the like ([0053]).
KR 20190002079 further teaches that the composition is a cosmetic composition (claims 12-13).
As such, the instant claims are anticipated by KR 20190002079.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 25-31 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over US 2018/0055894 in view of Ohno et al. (Int. J. Mol. Sci. 2016, 17, 172).
US 2018/0055894 teaches a method for preventing or treating an inflammatory disease, which comprises administering a composition comprising lactic acid bacteria-derived extracellular vesicles (EV) as active ingredients to a subject wherein the lactic acid bacteria is Lactobacillus plantarum ([0031] and claims 40 and 43-44).
US 2018/0055894 further teaches that the inflammatory disease includes atopic dermatitis, chronic rhinitis, chronic rhinosinusitis, asthma, chronic obstructive pulmonary disease (COPD), and sepsis (immune diseases) (claim 44). Chronic obstructive pulmonary disease (COPD) is one of lung disease recited in claim 26.
US 2018/0055894 specifically disclose that the EVs isolated by the method of the present invention may have an average diameter of 10 to 300 nm, and preferably 10 to 200 nm ([0020] and [0091]).
US 2018/0055894 teaches that the EVs may be isolated from a culture medium of lactic acid bacteria or food fermented with the lactic acid bacteria ([0021] and [0089]).
US 2018/0055894 teaches that the EVs are naturally or artificially secreted from lactic acid bacteria ([0022] and [0089]).
US 2018/0055894 discloses that the composition is a health functional food or a pharmaceutical composition ([0013] and [0015]).
US 2018/0055894 does not specifically the use of EV for delivering a desired immune disease or metabolic disease drug recited in claim 34.
However, the use of EVs for drug delivery has been known in the art as evidenced by Ohno et al. (abstract). Ohno et al. teach EVs as carriers for drug-delivery systems (DDSs), taking advantage of EVs’ natural characteristics to deliver molecules to target cells and the encapsulated molecules are protected from multiple types of degradative enzymes in body fluids, making EVs ideal for delivering drugs (abstract and p2, para 1-2, and Figure 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the lactic acid bacteria-derived EV for carrying a desired immune disease or metabolic disease drug for treating immune disease or metabolic disease because the Lactobacillus plantarum derived EV itself is taught to be beneficial for treating such diseases by US 2018/0055894 and the skilled artisan would have recognized that it would be useful for delivering a desired immune disease or metabolic disease drug as well as taught by Ohno et al. One of ordinary skill in the art would have been motivated to do so on the reasonable expectation that it would provide combined effects with improved delivery of such drugs in the treatment of immune disease or metabolic disease.
Double Patenting Rejections
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 25-31 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claim 1 of US patent 10406184.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claim of ‘184 patent are also drawn to a method of treating an inflammatory disease comprising: administering a pharmaceutical composition comprising the same Lactobacillus plantarum derived extracellular vesicles as an active ingredient to a subject in need thereof, wherein the composition does not contain the cells of Lactobacillus plantarum, and the inflammatory disease is selected from the group consisting of atopic dermatitis, chronic rhinitis, chronic rhinosinusitis, asthma, chronic obstructive pulmonary disease (COPD), and sepsis (immune disease).
As such, the instant claims are anticipated by or would have been obvious over the claim of the patent.
Conclusion
No claims are allowed.
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/BONG-SOOK BAEK/Primary Examiner, Art Unit 1611