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
This application has an effective filing date of February 19, 2024, with foreign priority application TW112138931, filed October 12, 2023. Applicant’s submission of claims filed February 19, 2024 is acknowledged. Claims 1-20 are pending and under examination.
Claim Objections
Claims 2, 9, and 16 are objected to because of the following informalities: in claims 2, 9, and 16, line 1, need to delete the second “retinal damage” phrase, since this is redundant. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-20 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
It is apparent that Lactobacillus plantarum PL-02 strain with deposit number CGMCC 20485, Lactobacillus salivarius subsp. salicinius AP-32 strain with deposit number CGMCC M2011127, Lactobacillus plantarum LPL28 strain with deposit number CGMCC 17954, Bifidobacterium longum subsp. infantis BLI-02 strain with deposit number CGMCC 15212, and Lactobacillus acidophilus TYCA06 strain with deposit number CGMCC 15210, are required to practice the claimed invention. As such the 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 aforementioned strains. The process disclosed in the specification does not appear to be repeatable, it is not clear that the invention will work with commonly available material and it is not apparent if the biological materials considered necessary to make and use the invention is both known and readily available to the public. Therefore, a deposit at a recognized depository may be made to obviate this rejection.
If the deposit is made under the terms of the Budapest Treaty, then a statement, affidavit or declaration by Applicants, or by an attorney of record over his or her signature and registration number, or by someone in a position to corroborate the facts of the deposit, that the instant invention will be irrevocably and without restriction released to the public upon the issuance of a patent, would satisfy the deposit requirement made herein.
If the deposit is a non-Budapest Treaty deposit, then in order to certify that the deposit meets the requirements set forth in 37 CFR 1.801-1.809 and MPEP 2402-2411.05, a statement, affidavit or declaration by Applicant or by an attorney of record over his or her signature and registration number, or by someone in a position to corroborate the facts of the deposit would satisfy the requirements herein by stating and providing that:
(a) During the pendency of the application, access to the invention will be afforded to the Commissioner upon request;
(b) All restrictions upon availability to the public will be irrevocably removed upon granting of the patent;
(c) The deposit will be maintained in a public depository for a period of 30 years, or 5 years after the last request or for the enforceable life of the patent, whichever is longer; and
(d) Provide evidence of the test of the viability of the biological material at the time of deposit (see 37 CFR 1.807).
The applicant did provide a certified translated copy of the deposit certificates from China General Microbiological Culture Collection Center on 02/19/2024, but failed to include the required statement as set forth above in (b).
Claims 1-20 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 method for repairing or preventing retinal damage including age-related macular degeneration and retinal damage caused by blue-light irradiation by administering compositions comprising Lactobacillus plantarum PL-02 strain, Lactobacillus salivarius subsp. salicinius AP-32 strain, Lactobacillus plantarum LPL28 strain, Bifidobacterium longum subsp. infantis BLI-02 strain, and Lactobacillus acidophilus TYCA06 strain to a subject in need thereof, does not reasonably provide enablement for a method for repairing or preventing any type of retinal damage by administering compositions comprising the recited strains. 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.
The breadth of the claims:
Claims 1-20 are drawn to a method for repairing or preventing any type of retinal damage by administering a composition comprising PL-02 or comprising PL-02, AP-32, LPL28, BLI-02, and TYCA06 to a subject in need thereof. The specification discloses the retinal damage can be caused by blue-light irradiation, and may also include macular degeneration, retinitis pigmentosa, diabetic retinopathy, non-proliferative diabetic retinopathy, proliferative diabetic retinopathy, hypertensive retinopathy, retinopathy of prematurity, radiation retinopathy, or solar retinopathy. The breadth of the claims encompass any type of retinal damage, including physical injuries that cause retinal hemorrhages or genetic/innate manifestations that lead to retinal damage. Thus, the claims are broad in that they include a large number of conditions of retinal damage which would not be expected to be treated in the same manner with the same agents.
The nature of the invention:
The nature of the invention relies upon administering compositions comprising the recited strains on human retinal pigment epithelial cells (RPE) to repair retinal damage caused by blue-light irradiation.
The state of the prior art:
Whether the specification would have been enabling as of the filing date involves consideration of the nature of the invention, the state of the prior art, and the level of skill in the art. The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed. See MPEP § 2164.05(b). The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification.
A thorough review of the patent and non-patent literature indicates that the state of the art demonstrating administering these strains to repair or prevent any type of retinal damage is variable. Osborne et al (Progress in Retinal and Eye Research 23 (2004) pgs. 91–147) discloses retinal ischemia as a pathological situation involving an inadequacy (not necessarily a complete lack of) blood flow to a tissue, with failure to meet cellular energy demands, and may be caused by general circulatory failure such as severe left ventricular failure and hypovolemic shock, or more commonly by local circulatory failure (pg. 93, col. 1, para 1-3), thus treatment by administering probiotics would not necessarily lead to sufficient retinal blood supply.
Georgiou et al. (Clin Experiment Ophthalmol. 2021; 49: pgs. 270–288) discloses the inherited retinal disease Best disease (BD) as the second commonest macular degeneration disease caused by recessive alleles in BEST1, wherein symptoms of acute visual loss and retinal hemorrhage are complicated by choroidal neovascularization, and treatment with anti-vascular endothelial growth factor (VEGF) have been found to be effective with improvement in structure and functional measurements (pg. 272, sec. 2.3), which underscores the variety of treatments used in treating retinal damage in different disease manifestations.
Jarrett et al. (Molecular Aspects of Medicine 33 (2012) 399–417) teaches retinal exposed to blue light undergoes intersystem crossing and forms a triplet state and singlet oxygen is produced, and age-related accumulation of the age pigment lipofuscin within the RPE is strongly associated with AMD, wherein ROS production is strongly dependent on the visible wavelength of light since highest levels of ROS were generated when lipofuscin was exposed to blue light compared to longer wavelengths (pg. 408, para 4). Jarrett teaches a mitochondrial-targeted MitoQ antioxidant protects RPE cells from blue light-induced oxidative stress (pg. 410, para 3), thus supports antioxidant applications in the prevention of retinal damage seen in AMD. As further outlined in the 103 rejection below, the prior art supports the antioxidant and anti-inflammatory properties of the specified strains used in the claimed compositions.
As stated above, the term “retinal damage” encompasses a wide range of conditions, including physical injury, inherited genetic diseases, vascular diseases, and damage caused by blue-light irradiation. The art does not reasonably support prevention and/or repair of all the conditions which fall within these categories of retinal damage by administering the recited strains and their metabolites.
Thus, a review of the prior art does not find a correlation between administering the recited strains and repairing and preventing the full scope of all retinal damage.
The level of one of ordinary skill and predictability in the art:
While the level of one of ordinary skill practicing said invention would be high, the level of predictability is considered variable as evident in the prior art discussed above and is not considered to provide sufficient enablement to practice the claimed invention. Because the state of the prior art does not provide evidence of the degree of predictability that methods for repairing or preventing all retinal damage by administering a composition comprising PL-02 or comprising PL-02, AP-32, LPL28, BLI-02, and TYCA06 to a subject in need thereof, one of ordinary skill in the art would look for guidance or direction in the instant specification.
“The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability.” (MPEP 2164.03). In the instant case, the various conditions that fall within the scope of “retinal damage” would require different treatment methods.
The amount of direction provided by the inventor and existence of working examples:
The instant application describes in vitro tests for reducing cell damage caused by blue light for single and mixture of bacterial strains, wherein the strains are incubated with human colorectal adenocarcinoma Caco-2 cells to model the oral administration of the probiotic, then a supernatant is obtained from the cultured bacterial cells and incubated with human retinal pigment epithelial cells ARPE-19 that are irradiated overnight, and found PL-02 increased survival rate of ARPE-19 by 79%, BLI-02 by 72%, and LPL28 by 70%, and the mixture increased the survival rate between 68%-82%.
The working embodiments do not describe any other type of retinal damage, and how administering the probiotic strains would effectively repair or prevent those conditions, only describing repairing retinal damage of ARPE-19 caused by blue light-irradiation. While the MPEP 2164.02 states the specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
The prior art is undeveloped for the role that the recited probiotic strains play in repairing or preventing all types of retinal damage, and given the broad scope of the claims and the different conditions encompassed, it is unpredictable if administering the recited strains would reasonably repair or prevent all types of retinal damage. The specification does not provide sufficient guidance on administering the recited strains in the repairment or prevention of the full scope of all retinal damage. Rather the specification merely describes examples related to the survival rate of blue light-irradiated ARPE-19 cells with the recited strains. The prior art also does not provide additional guidance to enable repairing or preventing retinal damage within the full scope of the claims.
Therefore, due to the unpredictability in the art with respect to repairing or preventing retinal damage within the full scope of the conditions which wouldn’t necessarily be caused by blue light-irradiation or age-related macular damage, one would have to engage in experimentation that is not reasonable in order to determine which of the various conditions could be treated by administering the recited strains.
Without further guidance, one of skill in the art would have to practice a substantial amount of trial-and-error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 15 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 15 depends on claim 14, and recites the same colony forming unit ratios as those recited in claim 14, thus does not further limit the claims. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Ho et al. (TW 202218674 A, hereinafter “Ho”) in view of Jarrett et al. (Molecular Aspects of Medicine 33 (2012) 399–417, hereinafter “Jarrett”).
Regarding claims 1 and 3, Ho teaches an anti-aging composition, the composition including: (a) isolated strains of lactic acid bacteria or a ferment thereof; and (b) an excipient, a diluent, or a carrier, wherein the isolated strains of lactic acid bacteria comprise: Bifidobacterium longum subsp. longum OLP-01 strains, Bifidobacterium animalis subsp. lactis CP-9 strains, Bifidobacterium longum BLI-02 strains, Bifidobacterium breve Bv-889 strains, Bifidobacterium bifidum Bf-688 strains, and Lactobacillus plantarum PL-02 strains (abstract). Ho teaches oxidative free radicals are one of the main factors causing the aging of organs in the body and taking a mixture of strains and their fermented products can not only enhance the effect of neutralizing oxidative substances in the body but also enhance the purpose of delaying aging. (pg. 2, para 1, 3). Ho teaches the aforementioned strains have high antioxidant activity compared with other probiotic strains (Examples 3-5). Ho teaches in Example 5, mice were administered a 1:1:1:1:1:1 mixture of strains (including PL-02 and BLI-02), and found statistically different markers of reduced oxidative substances and increased antioxidative catalase in the mice taking high doses of the lactic acid bacteria (pg. 6-7).
Ho does not teach a method for repairing or preventing retinal damage, specifically age-related macular degeneration.
However, Jarrett teaches consequences of oxidative stress in age-related macular degeneration, and discloses the retina resides in an environment that is primed for the generation of reactive oxygen species (ROS) and resultant oxidative damage, the retina being one of the highest oxygen-consuming tissues in the human body (abstract). Jarrett teaches as we age oxidative damage increases, antioxidant capacity decreases and the efficiency of reparative systems become impaired, resulting in retinal dysfunction and cell loss leading to visual impairment, thus these age-related oxidative changes are a hallmark of early age-related macular degeneration (AMD) which, in combination with hereditary susceptibility and other retinal modifiers, can progress to the pathology and visual morbidity associated with advanced AMD (abstract). Jarrett teaches the major enzymic antioxidants are superoxide dismutase, catalase and glutathione peroxidase, wherein catalase is an iron-dependent enzyme that directly scavenges H2O2 (2H2O2 → 2H2O + O2) (pg. 404, sec. 3.1).
Therefore, 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 utilize the anti-aging composition comprising L. plantarum PL-02 that increases catalase as taught by Ho in a method for repairing or preventing retinal damage caused by oxidative stress in age-related macular degeneration as taught by Jarrett. One of ordinary skill in the art would have been motivated to administer the PL-02 strain known for increasing catalase, as an effective treatment in repairing or preventing retinal damage in age-related macular degeneration as disclosed by Jarrett.
Regarding claims 4-5, Ho teaches composition can be a pharmaceutical composition can be in an oral dosage form or a skin external dosage form, which meets the limitation of claim 4 (pg. 4, para 3). Ho teaches the composition can be in the form of a food composition, the physiologically acceptable excipient, diluent or carrier can be a food product such as a dairy drink, tea, coffee, candy (e.g. lozenges, chewable lozenges, gummies), functional drinks or any combination of the above, wherein the dairy drinks can be fermented milk, yogurt, cheese or milk powder, etc., which meets the limitation of claim 5 (pg. 4, para 1).
Regarding claims 2 and 6, Ho does not teach a method of repairing or preventing retinal damage caused by blue-light irradiation in human pigment epithelial cells.
However, Jarrett teaches mitochondrial oxidative stress is further enhanced by phagocytosis of photoreceptor outer segments, presumably through the burst of ROS generated during ingestion, and by exposure to blue light (pg. 407, para 2). Jarrett teaches photochemical damage in retinal pigment epithelial cells (RPE) can be a ham type damage, often referred to as blue light damage, that is caused by relatively high irradiances and short exposures (seconds to minutes) and is considered to originate in the RPE (pg. 408, para 3). Jarrett teaches retinal exposed to blue light undergoes intersystem crossing and forms a triplet state and singlet oxygen is produced, and age-related accumulation of the age pigment lipofuscin within the RPE is strongly associated with AMD, wherein ROS production is strongly dependent on the visible wavelength of light since highest levels of ROS were generated when lipofuscin was exposed to blue light compared to longer wavelengths (pg. 408, para 4). Jarrett teaches a mitochondrial-targeted MitoQ antioxidant protects RPE cells from blue light-induced oxidative stress (pg. 410, para 3).
Therefore, 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 utilize the anti-aging composition comprising L. plantarum PL-02 that increases the antioxidant catalase as taught by Ho in a method for repairing or preventing retinal damage caused by oxidative stress due to blue light irradiation in RPE as taught by Jarrett. One of ordinary skill in the art would have been motivated to administer the PL-02 strain known for increasing catalase and having high antioxidant capacity as taught by Ho, as an effective treatment in repairing or preventing retinal damage due to ROS caused by blue-light irradiation in RPE as disclosed by Jarrett.
Claims 7-8, 10-12, 14-15, 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Ho (TW 202218674 A) in view of Liu et al. (US20210275612A1, hereinafter “Liu”) and Jarrett (Molecular Aspects of Medicine 33 (2012) 399–417).
Regarding claims 7-8, 10, 14-15, and 17, Ho teaches an anti-aging composition, the composition including: (a) isolated strains of lactic acid bacteria or a ferment thereof; and (b) an excipient, a diluent, or a carrier, wherein the isolated strains of lactic acid bacteria comprise: Bifidobacterium longum subsp. longum OLP-01 strains, Bifidobacterium animalis subsp. lactis CP-9 strains, Bifidobacterium longum BLI-02 strains, Bifidobacterium breve Bv-889 strains, Bifidobacterium bifidum Bf-688 strains, and Lactobacillus plantarum PL-02 strains (abstract). Ho teaches oxidative free radicals are one of the main factors causing the aging of organs in the body and taking a mixture of strains and their fermented products can not only enhance the effect of neutralizing oxidative substances in the body, but also enhance the purpose of delaying aging. (pg. 2, para 1, 3). Ho teaches the aforementioned strains have high antioxidant activity compared with other probiotic strains (Examples 3-5). Ho teaches in Example 5, mice were administered a 1:1:1:1:1:1 mixture of strains (including PL-02 and BLI-02), and found statistically different markers of reduced oxidative substances and increased antioxidative catalase in the mice taking high doses of the lactic acid bacteria (pg. 6-7).
Ho does not teach Lactobacillus salivarius subsp. salicinius AP-32 strain, Lactobacillus plantarum LPL28 strain, and Lactobacillus acidophilus TYCA06 strain in the composition.
However, Liu teaches a method for alleviating an inflammation-related disorder by administering at least one lactic acid bacterial strain selected from the group consisting of Lactobacillus plantarum LPL28 under accession number CGMCC 17954, Lactobacillus acidophilus TYCA06 (BCRC 910813), and Lactobacillus salivarius subsp. salicinius AP-32 (BCRC 910437) (claims 1 and 9). Liu teaches effect of liquid culture of LPL28 strain on interleukin-10 and TGF-β (both anti-inflammatory cytokines) production of human PBMCs were higher than the control group, thus can alleviate an inflammation-related disorder [0067-0073].
Neither Ho nor Liu teach a method for repairing or preventing retinal damage, specifically age-related macular degeneration.
However, Jarrett teaches consequences of oxidative stress in age-related macular degeneration, and discloses the retina resides in an environment that is primed for the generation of reactive oxygen species (ROS) and resultant oxidative damage, the retina being one of the highest oxygen-consuming tissues in the human body (abstract). Jarrett teaches as we age, oxidative damage increases, antioxidant capacity decreases, and the efficiency of reparative systems become impaired, resulting in retinal dysfunction and cell loss leading to visual impairment, thus these age-related oxidative changes are a hallmark of early AMD which, in combination with hereditary susceptibility and other retinal modifiers, can progress to the pathology and visual morbidity associated with advanced AMD (abstract). Jarrett teaches pro-inflammatory cytokines, tumor necrosis factor-a, interleukin-1b, and interferon-γ, induce ROS in RPE cells via mitochondria and NADPH oxidase (pg. 408, sec. 5.2). Jarrett teaches the major enzymic antioxidants are superoxide dismutase, catalase, and glutathione peroxidase, wherein catalase is an iron-dependent enzyme that directly scavenges H2O2 (2H2O2 → 2H2O + O2) (pg. 404, sec. 3.1).
Therefore, 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 combine the anti-aging composition comprising L. plantarum PL-02 and B. longum BLI-02 that increases catalase as taught by Ho with the anti-inflammatory composition comprising L. salivarius AP-32, L. acidophilus TYCA06 (BCRC 910813), and L. plantarum LPL28 that induces anti-inflammatory cytokines taught by Liu, to be used in a method for repairing or preventing retinal damage caused by oxidative stress that is induced by pro-inflammatory cytokines in AMD as taught by Jarrett. One of ordinary skill in the art would have been motivated to combine and administer these strains known for increasing catalase and anti-inflammatory cytokines, as an effective treatment in repairing or preventing retinal damage in AMD as disclosed by Jarrett.
Ho teaches in Example 5 anti-aging analysis of a lactic acid bacteria mixture comprising Bifidobacterium longum subsp. longum subsp. longum OLP-01 strain, Bifidobacterium breve Bv-889 strain, Lactobacillus plantarum PL-02 strain, and Bifidobacterium longum BLI-02 strain, with the number ratio of strains as 1:1:1:1:1:1 (pg. 6, para 6). Ho teaches the mice were fed with low-dose LAB mixture at 1.03 x 109 CFU/kg and high-dose LAB mixture 4.1 x 109 CFU/kg (pg. 6, para 6). Although Ho does not teach the specific CFU% of each strain in the mixture or CFU ratio as recited in the claims, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Regarding claims 11-12 and 18-19, Ho teaches composition can be a pharmaceutical composition can be in an oral dosage form or a skin external dosage form (pg. 4, para 3). Ho teaches the composition can be in the form of a food composition, the physiologically acceptable excipient, diluent or carrier can be a food product such as a dairy drink, tea, coffee, candy (e.g. lozenges, chewable lozenges, gummies), functional drinks or any combination of the above, wherein the dairy drinks can be fermented milk, yogurt, cheese or milk powder, etc. (pg. 4, para 1). Liu teaches the composition can be formulated into a suitable dosage form for oral or topical administration, or formulated as a food product [0043, 0047-0049]. Thus, combining the compositions taught by Ho and Liu into formulated medicinal or nutritional compositions that can be administered orally or topically or in the form of food would have been prima facie obvious to one of ordinary skill in the art and would have been a well-understood and routine practice in the industry.
Claims 9, 13, 16, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Ho in view of Liu and Jarrett as applied to claims 7-8, 10-12, 14-15, 17-19 above, and further in view of Morita et al. (Nutrients 2018, 10, 1991, hereinafter “Morita”).
As discussed above, Ho and Liu teach compositions comprising the recited strains that have antioxidant and anti-inflammatory properties useful in treating aging and inflammatory disorders. Neither Ho nor Liu teach a method of repairing or preventing retinal damage caused by blue-light irradiation in RPE cells.
However, Jarrett teaches mitochondrial oxidative stress is further enhanced by phagocytosis of photoreceptor outer segments, presumably through the burst of ROS generated during ingestion, and by exposure to blue light (pg. 407, para 2). Jarrett teaches photochemical damage in retinal pigment epithelial cells (RPE) can be a ham type damage, often referred to as blue light damage, that is caused by relatively high irradiances and short exposures (seconds to minutes) and is considered to originate in the RPE (pg. 408, para 3). Jarrett teaches retinal exposed to blue light undergoes intersystem crossing and forms a triplet state and singlet oxygen is produced, and age-related accumulation of the age pigment lipofuscin within the RPE is strongly associated with AMD, wherein ROS production is strongly dependent on the visible wavelength of light since highest levels of ROS were generated when lipofuscin was exposed to blue light compared to longer wavelengths (pg. 408, para 4). ). Jarrett teaches a mitochondrial-targeted MitoQ antioxidant protects RPE cells from blue light-induced oxidative stress (pg. 410, para 3).
Morita teaches Lactobacillus paracasei KW3110 prevents blue light-induced inflammation and degeneration in the retina (title). Morita teaches AMD and retinitis pigmentosa are leading causes of blindness and share a pathological feature, which is photoreceptor degeneration, wherein photoreceptor degeneration can be accelerated by excessive light exposure via an inflammatory response; therefore, anti-inflammatory agents would be candidates to prevent the progress of photoreceptor degeneration (abstract). Morita teaches L. paracasei KW3110 activated M2 macrophages inducing anti-inflammatory cytokine interleukin-10 (IL-10) production in vitro using bone marrow-derived M2 macrophages (abstract). Morita also showed IL-10 gene expression was significantly increased in the intestinal immune tissues 6 h after oral administration of L. paracasei KW3110 in vivo, demonstrating that intake of L. paracasei KW3110 suppressed inflammation and photoreceptor degeneration in a murine model of light-induced retinopathy, suggesting that L. paracasei KW3110 may have a preventive effect against degrative retinal diseases (abstract).
Therefore, 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 combine the composition comprising L. plantarum PL-02 and B. longum BLI-02 that increases the antioxidant catalase as taught by Ho with the anti-inflammatory composition comprising L. salivarius AP-32, L. acidophilus TYCA06 (BCRC 910813), and L. plantarum LPL28 that induces anti-inflammatory cytokines taught by Liu, to be used in a method for repairing or preventing retinal damage caused blue-light irradiation in RPE due to oxidative stress and pro-inflammatory cytokines as taught by Jarrett and Morita. One of ordinary skill in the art would have been motivated to combine and administer these strains known for increasing the antioxidant catalase and anti-inflammatory cytokines, as an effective treatment in repairing or preventing retinal damage in RPE caused by blue light-irradiation as disclosed by Jarrett and Morita.
Double Patenting
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 1-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,957,722B2 in view of Jarrett.
Regarding instant claims 1 and 3, ‘722 recites a method for anti-aging comprising administering (a) isolated lactic acid bacterial strains; and (b) an excipient, a diluent, or a carrier; wherein the isolated lactic acid bacterial strains include: a Bifidobacterium bifidum VDD088 strain deposited at the China General Microbiological Culture Collection Center with an accession No. CGMCC 15211, a Bifidobacterium breve Bv-889 strain deposited at the China General Microbiological Culture Collection Center with an accession No. CGMCC 16145, a Bifidobacterium longum BLI-02 strain deposited at the China General Microbiological Culture Collection Center with an accession No. CGMCC 15212, a Bifidobacterium animalis sub sp. lactis CP-9 strain deposited at the China Center for Type Culture Collection with an accession No. CCTCC M2014588, and a Lactobacillus plantarum PL-02 strain deposited at the China General Microbiological Culture Collection Center with an accession No. CGMCC 20485. Claim 3 of ‘722 recites the composition is administered for scavenging free radicals, inhibiting P21 gene expression, reducing protein carbonyl contents, enhancing catalase activity, or reducing 8-oxo-2′-deoxyguanosine contents in a body of the subject. ‘722 does not recite administering the composition in a method for repairing or preventing retinal damage, specifically AMD.
However, Jarrett teaches consequences of oxidative stress in age-related macular degeneration, and discloses the retina resides in an environment that is primed for the generation of reactive oxygen species (ROS) and resultant oxidative damage, the retina being one of the highest oxygen-consuming tissues in the human body (abstract). Jarrett teaches as we age oxidative damage increases, antioxidant capacity decreases and the efficiency of reparative systems become impaired, resulting in retinal dysfunction and cell loss leading to visual impairment, thus these age-related oxidative changes are a hallmark of early age-related macular degeneration (AMD) which, in combination with hereditary susceptibility and other retinal modifiers, can progress to the pathology and visual morbidity associated with advanced AMD (abstract). Jarrett teaches the major enzymic antioxidants are superoxide dismutase, catalase and glutathione peroxidase, wherein catalase is an iron-dependent enzyme that directly scavenges H2O2 (2H2O2 → 2H2O + O2) (pg. 404, sec. 3.1).
Therefore, 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 utilize the anti-aging composition comprising L. plantarum PL-02 that increases catalase as recited by ‘722 in a method for repairing or preventing retinal damage caused by oxidative stress in age-related macular degeneration as taught by Jarrett. One of ordinary skill in the art would have been motivated to administer the PL-02 strain known for increasing catalase as recited in ‘722, as an effective treatment in repairing or preventing retinal damage in age-related macular degeneration as disclosed by Jarrett.
Regarding instant claims 2 and 6, ‘722 does not recite a method of administering PL-02 for repairing or preventing retinal damage caused by blue-light irradiation.
However, Jarrett teaches mitochondrial oxidative stress is further enhanced by phagocytosis of photoreceptor outer segments, presumably through the burst of ROS generated during ingestion, and by exposure to blue light (pg. 407, para 2). Jarrett teaches photochemical damage in retinal pigment epithelial cells (RPE) can be a ham type damage, often referred to as blue light damage, that is caused by relatively high irradiances and short exposures (seconds to minutes) and is considered to originate in the RPE (pg. 408, para 3). Jarrett teaches retinal exposed to blue light undergoes intersystem crossing and forms a triplet state and singlet oxygen is produced, and age-related accumulation of the age pigment lipofuscin within the RPE is strongly associated with AMD, wherein ROS production is strongly dependent on the visible wavelength of light since highest levels of ROS were generated when lipofuscin was exposed to blue light compared to longer wavelengths (pg. 408, para 4). Jarrett teaches a mitochondrial-targeted MitoQ antioxidant protects RPE cells from blue light-induced oxidative stress (pg. 410, para 3).
Therefore, 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 utilize the anti-aging composition comprising L. plantarum PL-02 that increases the antioxidant catalase as recited in ‘722 in a method for repairing or preventing retinal damage caused by oxidative stress due to blue light irradiation in RPE as taught by Jarrett. One of ordinary skill in the art would have been motivated to administer the PL-02 strain known for increasing catalase and having high antioxidant capacity as recited in ‘722, as an effective treatment in repairing or preventing retinal damage due to ROS caused by blue-light irradiation in RPE as disclosed by Jarrett.
Regarding instant claims 4-5, claim 1 of ‘722 recites the composition comprises an excipient, diluent, or carrier, but does not explicitly recite it is administered via oral administration in the form of food. However, formulating probiotics for oral administration in the form of food is a well-understood and routine practice in the art, and would be obvious for one of ordinary skill in the to incorporate as in the instant method.
Claims 7-8, 10-12, 14-15, 17-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,957,722B2 in view of Liu and Jarrett.
Regarding claims 7-8, 10, 14-15, and 17, ‘722 recites an anti-aging composition, the composition including: (a) isolated strains of lactic acid bacteria or a ferment thereof; and (b) an excipient, a diluent, or a carrier, wherein the isolated strains of lactic acid bacteria comprise: Bifidobacterium longum subsp. longum OLP-01 strains, Bifidobacterium animalis subsp. lactis CP-9 strains, Bifidobacterium longum BLI-02 strains, Bifidobacterium breve Bv-889 strains, Bifidobacterium bifidum Bf-688 strains, and Lactobacillus plantarum PL-02 strains (abstract). Claim 3 of ‘722 recites the composition is administered for scavenging free radicals, inhibiting P21 gene expression, reducing protein carbonyl contents, enhancing catalase activity, or reducing 8-oxo-2′-deoxyguanosine contents in a body of the subject. Claims 5-6 of ‘722 recite the composition has a total bacterial count from 106 to 1010 CFU/kg of body weight of the subject/day or from 8.3×107 to 3.4×108 CFU/kg of body weight of the subject/day. ‘722 discloses in Example 5, mice were administered a 1:1:1:1:1:1 mixture of strains (including PL-02 and BLI-02), and found statistically different markers of reduced oxidative substances and increased antioxidative catalase in the mice taking high doses of the lactic acid bacteria (pg. 6-7). ‘722 does not teach a composition comprising Lactobacillus salivarius subsp. salicinius AP-32 strain, Lactobacillus plantarum LPL28 strain, and Lactobacillus acidophilus TYCA06 strain.
However, Liu teaches a method for alleviating an inflammation-related disorder by administering at least one lactic acid bacterial strain selected from the group consisting of Lactobacillus plantarum LPL28 under accession number CGMCC 17954, Lactobacillus acidophilus TYCA06 (BCRC 910813), and Lactobacillus salivarius subsp. salicinius AP-32 (BCRC 910437) (claims 1 and 9). Liu teaches effect of liquid culture of LPL28 strain on interleukin-10 and TGF-β (both anti-inflammatory cytokines) production of human PBMCs were higher than the control group, thus can alleviate an inflammation-related disorder [0067-0073].
Neither ‘722 recites nor Liu teach a method for repairing or preventing retinal damage, specifically age-related macular degeneration.
However, Jarrett teaches consequences of oxidative stress in age-related macular degeneration, and discloses the retina resides in an environment that is primed for the generation of reactive oxygen species (ROS) and resultant oxidative damage, the retina being one of the highest oxygen-consuming tissues in the human body (abstract). Jarrett teaches as we age, oxidative damage increases, antioxidant capacity decreases, and the efficiency of reparative systems become impaired, resulting in retinal dysfunction and cell loss leading to visual impairment, thus these age-related oxidative changes are a hallmark of early AMD which, in combination with hereditary susceptibility and other retinal modifiers, can progress to the pathology and visual morbidity associated with advanced AMD (abstract). Jarrett teaches pro-inflammatory cytokines, tumor necrosis factor-a, interleukin-1b, and interferon-γ, induce ROS in RPE cells via mitochondria and NADPH oxidase (pg. 408, sec. 5.2). Jarrett teaches the major enzymic antioxidants are superoxide dismutase, catalase, and glutathione peroxidase, wherein catalase is an iron-dependent enzyme that directly scavenges H2O2 (2H2O2 → 2H2O + O2) (pg. 404, sec. 3.1).
Therefore, 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 combine the anti-aging composition comprising L. plantarum PL-02 and B. longum BLI-02 that increases catalase as recited by ‘722 with the anti-inflammatory composition comprising L. salivarius AP-32, L. acidophilus TYCA06 (BCRC 910813), and L. plantarum LPL28 that induces anti-inflammatory cytokines taught by Liu, to be used in a method for repairing or preventing retinal damage caused by oxidative stress that is induced by pro-inflammatory cytokines in AMD as taught by Jarrett. One of ordinary skill in the art would have been motivated to combine and administer these strains known for increasing catalase and anti-inflammatory cytokines, as an effective treatment in repairing or preventing retinal damage in AMD as disclosed by Jarrett.
‘722 discloses in Example 5 anti-aging analysis of a lactic acid bacteria mixture comprising Bifidobacterium longum subsp. longum subsp. longum OLP-01 strain, Bifidobacterium breve Bv-889 strain, Lactobacillus plantarum PL-02 strain, and Bifidobacterium longum BLI-02 strain, with the number ratio of strains as 1:1:1:1:1:1 (pg. 6, para 6). Ho teaches the mice were fed with low-dose LAB mixture at 1.03 x 109 CFU/kg and high-dose LAB mixture 4.1 x 109 CFU/kg (pg. 6, para 6). Although ‘722 does not recite the specific CFU% of each strain in the mixture or CFU ratio as recited in the instant claims, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Regarding claims 11-12 and 18-19, claim 1 of ‘722 recites the composition comprises an excipient, diluent, or carrier, but does not explicitly recite it is administered via oral administration in the form of food. However, formulating probiotics for oral administration in the form of food is a well-understood and routine practice in the art, and would be obvious for one of ordinary skill in the to incorporate as in the instant method. Similarly, Liu teaches the composition can be formulated into a suitable dosage form for oral or topical administration, or formulated as a food product [0043, 0047-0049]. Thus, combining the compositions recited by ‘722 and taught by Liu into formulated medicinal or nutritional compositions that can be administered orally or topically or in the form of food would have been prima facie obvious to one of ordinary skill in the art and would have been a well-understood and routine practice in the industry.
Claims 7-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,957,722B2 in view of Liu, Jarrett, and Morita.
As discussed above, instant claims 7-8, 10-12, 14-15, 17-19 are obvious over ‘722 in view of Liu and Jarrett. Neither ‘722 recites nor Liu teach a method of repairing or preventing retinal damage caused by blue-light irradiation in RPE cells.
However, Jarrett teaches mitochondrial oxidative stress is further enhanced by phagocytosis of photoreceptor outer segments, presumably through the burst of ROS generated during ingestion, and by exposure to blue light (pg. 407, para 2). Jarrett teaches photochemical damage in retinal pigment epithelial cells (RPE) can be a ham type damage, often referred to as blue light damage, that is caused by relatively high irradiances and short exposures (seconds to minutes) and is considered to originate in the RPE (pg. 408, para 3). Jarrett teaches retinal exposed to blue light undergoes intersystem crossing and forms a triplet state and singlet oxygen is produced, and age-related accumulation of the age pigment lipofuscin within the RPE is strongly associated with AMD, wherein ROS production is strongly dependent on the visible wavelength of light since highest levels of ROS were generated when lipofuscin was exposed to blue light compared to longer wavelengths (pg. 408, para 4). ). Jarrett teaches a mitochondrial-targeted MitoQ antioxidant protects RPE cells from blue light-induced oxidative stress (pg. 410, para 3).
Morita teaches Lactobacillus paracasei KW3110 prevent blue light-induced inflammation and degeneration in the retina (title). Morita teaches AMD and retinitis pigmentosa are leading causes of blindness and share a pathological feature, which is photoreceptor degeneration, wherein photoreceptor degeneration can be accelerated by excessive light exposure via an inflammatory response; therefore, anti-inflammatory agents would be candidates to prevent the progress of photoreceptor degeneration (abstract). Morita teaches L. paracasei KW3110 activated M2 macrophages inducing anti-inflammatory cytokine interleukin-10 (IL-10) production in vitro using bone marrow-derived M2 macrophages (abstract). Morita also showed IL-10 gene expression was significantly increased in the intestinal immune tissues 6 h after oral administration of L. paracasei KW3110 in vivo, demonstrating that intake of L. paracasei KW3110 suppressed inflammation and photoreceptor degeneration in a murine model of light-induced retinopathy, suggesting that L. paracasei KW3110 may have a preventive effect against degrative retinal diseases (abstract).
Therefore, 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 combine the composition comprising L. plantarum PL-02 and B. longum BLI-02 that increases the antioxidant catalase as recited by ‘722 with the anti-inflammatory composition comprising L. salivarius AP-32, L. acidophilus TYCA06 (BCRC 910813), and L. plantarum LPL28 that induces anti-inflammatory cytokines taught by Liu, to be used in a method for repairing or preventing retinal damage caused blue-light irradiation in RPE due to oxidative stress and pro-inflammatory cytokines as taught by Jarrett and Morita. One of ordinary skill in the art would have been motivated to combine and administer these strains known for increasing the anti-oxidant catalase and anti-inflammatory cytokines, as an effective treatment in repairing or preventing retinal damage in RPE caused by blue light-irradiation as disclosed by Jarrett and Morita.
Conclusion
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/JESSICA EDWARDS/
Examiner, Art Unit 1657
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