DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 1-20 are pending following the Reply filed 02/19/2026. Claims 1, 5-12, 14-15 and 18-20 have been amended without introducing new matter. All pending claims have been examined on the merits.
Withdrawn
The objection to claim 7 is withdrawn in light of the amendments.
The rejections of claims 1, 6-7, 9-11 and 18 under 35 U.S.C. 112(b) are withdrawn in light of the amendments.
The rejections of the claims under 35 U.S.C. 112(d) are withdrawn in light of the amendments.
The rejection made under 35 U.S.C. 112(a) has been withdrawn upon further consideration.
Claim Objections
Claim 10 is objected to because of the following informalities: the claim recites “the said composition” in line 1. This phrase should be amended to recite “the composition” or “said composition”. Either of which provides the same antecedent basis. Appropriate correction is required.
Claim 11 is objected to because of the following informalities: the claim recites “the said composition” in line 4. This phrase should be amended to recite “the composition” or “said composition”. Either of which provides the same antecedent basis. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8 and 19-20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 8 recites the limitation, “which may…be genetically modified to optimize the production of retinol” which renders the claim indefinite, because it is unclear if the limitation is reciting a method step (i.e., of genetically modifying the selected microorganism) or is a characteristic of the microorganism (i.e., wherein the microorganism is a genetically modified microorganism). Here, the phrase “which may be…modified to optimize” can be interpreted as requiring an active step of modifying the microorganism in order to achieve optimized production, but this phrasing can also be interpreted as merely reciting a characteristic of the microorganism selected for culturing.
Claim 19 recites the limitation "the formulation" in line 1. There is insufficient antecedent basis for this limitation in the claim.
In the interest of compact prosecution, the further limitation of claim 19 is interpreted as “wherein the product is a cosmetic product”.
Claim 20, which depends from claim 19, also recites the limitation “the formulation” in line 1, and is rejected for failing to obviate the indefiniteness of the parent claim.
In the interest of compact prosecution, the further limitations of claim 20 is interpreted as “wherein the cosmetic product is an anti-aging product”.
Claim Rejections - 35 USC § 112(a)—Written Description
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 and 9-20 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.
Brief Statement of the Issue(s)
The claims are directed to microorganisms capable of producing retinol in the presence of carnosic acid, wherein the specification fails to permit an ordinary artisan to envisage which microorganisms are capable of providing retinol and also fails to adequately disclose which microorganisms can do so without being inhibited by the presence of carnosic acid in culture. While the culturing of microorganisms in the presence of carnosic acid is unpredictable in view of the prior art of record, Applicant has failed to show possession of even a single representative species of the claimed invention.
Claim Scope
Claims 1 and 13 are representative of the pending claim scope and recite a process for preparing retinol compositions, wherein carnosic acid is added to a culture medium comprising a microorganism which is only defined as being “capable of providing retinol”.
Claim 3 recites the process of claim 1, wherein the carnosic acid is added in an amount that is “not toxic to the microorganism”.
As the “microorganism” of the present invention is only defined as “being capable of providing retinol”, it is unclear if the claim scope encompasses trillions of species or perhaps only a few in view of the functional limitations set forth in the claim(s). Accordingly, the claim scope reasonably appears to be vast and highly varied.
Actual Reduction to Practice
The examples of Applicant’s disclosure involve: (1) preparing a composition comprising sunflower oil, hydro-ethanolic rosemary extract, (2) adjusting the carnosic acid content of the mixture by the addition of oil, and (3) assessing the compositions at 1, 3 and 6 months to ascertain if retinol oxidation had occurred (see pg. 23, “Example” 1 & 2). Hence, the only reduction to practice did not include any microorganism or any process step of culturing said microorganism. Conversely, Applicant’s examples were merely used to demonstrate the effect of carnosic acid in preventing the oxidation of retinol. Accordingly, zero examples of the claimed invention were reduced to actual practice.
Assessment of whether disclosed species are representative of the claimed genus
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus (see, e.g., MPEP § 2163(II)(3)(a), MPEP §2163.03(V)). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In this case, the claims encompass an essentially infinite number of microorganisms, but zero were reduced to practice.
Although the MPEP does not define what constitutes a sufficient number of representative species, the Courts have indicated that the disclosure of two species within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618. Similarly, the disclosure of zero species of the claimed invention does not provide sufficient disclosure to satisfy the written description requirement for the instantly claimed genus.
Identifying characteristics of the genus
In the absence of a reduction to practice of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
The specification as filed merely states: (1) the nature of the microorganism is not limited as long as it is a microorganism capable of producing retinol, (2) the microorganism may be Yarrowia lipolytica or Saccharomyces cerevisiae, (3) the microorganism may be genetically modified to optimize the production retinol, and (4) “[e]xamples of suitable microorganisms are described in US 2022/017878 A1, the disclosure of which in this context is herewith incorporated by reference” (see pg. 9, lines 11-15).
The inventors of the recited reference, Yu et al. (US 2022/017878 A1; cited in the IDS filed 08/08/2023; hereafter, “Yu”), disclose a microorganism for producing retinol, wherein certain protein activities were enhanced (see pg. 1, para. [0005]). Similar to the present disclosure, Yu discloses that the “microorganism of the present invention is not limited, as long as it is a microorganism having an ability to produce retinol” and “may be Yarrowia lipolytica or Saccharomyces cerevisiae” (see pg. 6, para. [0064]). In Yu’s examples, Saccharomyces cerevisiae, a yeast strain widely used in recombinant protein production, was selected as a strain for producing retinol (see pg. 7, para. [0083]), but to prepare the strain for producing retinol, high-efficiency gene manipulation in this strain was required (see pg. 7, para. [0084]). Yu teaches the design of a GGPP-to-retinol metabolic pathway (GGPP[Wingdings font/0xE0]phytoene[Wingdings font/0xE0]
neurosporene[Wingdings font/0xE0]lycopene[Wingdings font/0xE0]β-carotene[Wingdings font/0xE0]retinal[Wingdings font/0xE0]retinol) which required nucleotide sequences encoding several heterologous genes (derived from other species) in this pathway to be synthesized for transforming the S. cerevisiae strain (see pg. 7, paras. [0086]-[0087]; pg. 8, para. [0092] and [0094]).
Zero discussion is provided in the originally filed disclosure identifying which other species are amenable to these genetic transformations or what other modifications would be required for these other species to produce retinol in a culture medium, particularly in the presence of carnosic acid. It would not be apparent to any skilled artisan, based on the disclosure of two genetically modified yeast strains, which culturable microorganisms (gram-positive bacteria, gram-negative bacteria, yeasts, non-yeast fungi, non-fungi eukaryotes, archaebacteria, etc.) are not only capable of being transformed by the methods taught by Yu, but can also be cultured in the presence of carnosic acid without toxic effects.
Accordingly, the functional limitation of “capable of providing retinol” is only utilized as a vague attempt to capture unknown and undisclosed structures, sufficient to achieve some functional result desired for the disclosed invention to achieve. However, the disclosure does not meaningfully disclose an unambiguous structure/function relationship permitting an artisan to identify, a priori, which exact structures do or do not satisfy the functional limitations at issue.
Predictability in the Art
According to Birtić et al. (cited in the IDS filed 08/08/2023; hereafter, “Birtic”), carnosic acid (salvin) possesses antioxidative and antimicrobial properties with potential applications within the food, nutritional health and cosmetics industries, but there is a deficiency in our current understanding of its relevant biochemical properties (see Abstract). Birtic discloses: (1) rosemary extracts rich in carnosic acid have been shown to have antimicrobial activity, (2) studies on various pathogens suggest that carnosic acid was the most active compound involved in this activity, (3) among 8 major rosemary phenolics, carnosic acid was shown to have the strongest antilisterial activity, (4) both Gram positive bacteria (e.g., Bacillus, Enterococcus, Streptococcus, Staphylococcus) and Gram negative bacteria (e.g., Escherichia, Salmonella, Campylobacter) are responsive to carnosic acid (see pg. 14, col. 1, para. 5 to col. 2, para. 1). Birtic teaches that while mechanisms involved in antimicrobial activities of phenolic diterpenes have not yet been elucidated, it has been suggested that the lipophilic structure of these compounds allows them to insert into the bacterial membrane (see pg. 14, col. 2, para. 1). According to Oreopoulou et al. (previously cited), the constituents of rosemary extracts, including carnosic acid and carnosol, have been associated with several antifungal and antimicrobial effects (see pg. 4, para. 2).
Similar to Yu’s disclosure, Kim et al. (US Patent No. 9,644,217 B2; previously cited) teach a method for producing retinoids from a microorganism (see Abstract), wherein the microorganism is of the genus Escherichia and may either be a laboratory strain that already produces retinoids (Escherichia coli strains DH5-alpha, MG1655, BL21, S17-1, XL1-Blue, BW25113) or one that has been transformed by genes associated with one or more retinoid syntheses pathways (see col. 2, lines 29-31, 50-56).
Hence, the prior art teaches that retinol production has been achieved in certain laboratory strains of yeast and E. coli by the careful manipulation of certain known genetic structures that collectively form one of several metabolic pathways that can be used to transform the microorganism to produce retinol. However, it would be apparent to a skilled artisan that the selection of these transformations are dependent on which metabolic genes in these pathways are already present or not present in the microorganism, and they would not be able to immediately envisage which strains can be transformed with which genes in order to produce retinol in a culture medium containing carnosic acid. Furthermore, a person of ordinary skill would not be able to immediately envisage what amounts of carnosic acid content in the culture medium would not be toxic for each and every possible member of this genus. This is a particular problem, because while the prior art teaches carnosic acid to have antioxidant effects, it also teaches it to have antimicrobial and antifungal effects and is otherwise silent on the use of carnosic acid in microbial culture media.
Although the level of skill in the art is high, the predictability in the art is low due to the complexity of biological systems and the lack of relevant teachings on using carnosic acid in culture media. Specifically, an artisan would not be able to predict or identify, a priori, and in the absence of any guidance or consensus structures exactly what microorganisms would be capable of providing retinol in a culture medium containing carnosic acid.
Accordingly, in the absence of sufficient structure/function teachings identifying particular microbial strains capable of providing retinol in the presence of carnosic acid, as required to practice the full scope of the claims, an artisan would not reasonably conclude that Applicant possessed the full scope of the broad and highly varied claim scope.
Conclusion
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). The courts have stated that “merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus” (see, e.g., AbbVie v. Janssen, 111 USPQ2d 1780 (Fed. Cir. 2014) at 1789). In addition, the Courts have stated
“[r]egardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
This is pertinent because, in the instant case, Applicants have claimed a broad and highly varied genus comprising an unknown number of species defined by reference to one or more functional limitations; however, the originally filed disclosure has failed to identify any common structure/function relationship sufficient to permit an artisan to identify what structures are included or excluded by the claim scope. This also means that the skilled artisan cannot envisage what structures infringe or do not infringe upon the pending claim scope.
In conclusion, for the reasons discussed above, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention.
Claim Rejections - 35 USC § 103
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.
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.
Claims 1-8 and 10-20 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (US 20220017878 A1; effectively filed 11/30/2018; cited in the IDS filed 08/08/2023), hereafter “Yu”, and further in view of Maiza et al. (cited in the IDS filed 08/08/2023), hereafter “Maiza”.
Regarding claim 1, Yu teaches a method of producing retinol, comprising culturing a microorganism, wherein the microorganism has an improved ability to produce retinal (see Abstract). Yu teaches retinol is a high-value-added raw material that has anti-wrinkle and antioxidant effects (see pg. 1, para. [0002]), but, despite its usefulness, production of retinol is not easy and has high production costs (see pg. 1, para. [0003]). Yu discloses the development of a microorganism capable of more stably producing retinol with high efficiency (see pg. 1, para. [0004]). Yu teaches the culture medium used for culturing the microorganism for producing retinol may contain oils and fats as a carbon source, such as “soybean oil, sunflower seed oil, peanut oil, and coconut oil” (see pg. 6, para. [0073]). Hence, Yu teaches a process of preparing a composition comprising retinol, the process comprising the step of culturing a microorganism capable of providing retinol in a culture medium comprising oil. As Yu teaches oil to be present in the culture medium, the composition produced by the method comprises retinol and oil.
In Yu’s examples, Saccharomyces cerevisiae, a yeast strain widely used in recombinant protein production, was selected as a strain for producing retinol (see pg. 7, para. [0083]), but to prepare the strain for producing retinol, high-efficiency gene manipulation in this strain was required (see pg. 7, para. [0084]). Yu teaches the design of a GGPP-to-retinol metabolic pathway (GGPP[Wingdings font/0xE0]phytoene[Wingdings font/0xE0]neurosporene[Wingdings font/0xE0]lycopene[Wingdings font/0xE0]β-carotene[Wingdings font/0xE0]retinal[Wingdings font/0xE0]retinol) which required nucleotide sequences encoding several heterologous genes in this pathway to be synthesized for transforming the S. cerevisiae strain (see pg. 7, paras. [0086]-[0087]; pg. 8, para. [0092] and [0094]).
Yu does not teach the process wherein carnosic acid is added to the culture medium.
Maiza’s study aims to characterize the effects of aromatic plants (rosemary and clove) on the nutritional, volatile and oxidative profile of cow ghee (see Abstract). Maiza teaches that one of the most widespread and well-known properties of ghee is its wound healing activity, due to its valuable content of fat-soluble vitamins, such as vitamin A (see pg. 8910, col. 1, para. 4). However, due to its high lipid content, ghee undergoes rapid auto-oxidation with a reduction of its shelf-life, which may be solved by adding antioxidants into ghee (see pg. 8910, col. 1, para. 4-5). Maiza teaches that due to their high content in phenolic compounds, rosemary and clove leaves are characterized by an important antioxidant activity, and can be used as plant extracts to prevent lipid oxidation in oily products (see pg. 8910, col. 2, para. 2). Maiza’s study evaluated the effect of plant enrichment on the vitamin composition of ghee; notably, the retinol content of the different ghee samples analyzed after 21 days showed that the highest level of retinol was observed in rosemary enriched ghee (see pg. 8913, col. 2, para. 3). Maiza teaches that rosemary-enriched samples showed higher levels of targeted phenolic compounds, the major compound present in all samples being carnosic acid (see pg. 8914, col. 1, para. 2). Maiza teaches that polyphenols contained in rosemary are released into the ghee matrix, increasing its oxidative stability (see pg. 8914, col. 2, para. 2). Maiza teaches that the results of this study suggest that ghee could be useful for skincare, especially when it is enriched with natural antioxidants from rosemary leaves (see pg. 8917, col. 1, para. 1).
In summary, Maiza teaches that rosemary extracts containing high carnosic acid content provide antioxidant effects to fat-soluble vitamins, such as vitamin A (i.e., retinol), and suggests that the retinol content of oily compositions can be significantly enhanced and preserved in the presence polyphenols, particularly carnosic acid, derived from rosemary.
Regarding predictability, as discussed under 35 U.S.C. 112(a), it would not have been predictable to have cultured any microorganism in the presence of carnosic acid due to the known antimicrobial effects of carnosic acid. However, Yu teaches the method of producing retinol may further include the step of recovering retinol from the medium using an appropriate method known in the art (see pg. 7, para. [0081]), wherein the term “medium” refers to both the culture medium for culturing the microorganism and the product obtained after culturing the same (see pg. 6, para. [0072]). Therefore, as Maiza teaches the stabilizing effects of carnosic acid in retinol-containing products, a person of skill would have recognized that carnosic acid could be added to the medium at a later stage of the process, wherein the viability of the microorganism is no longer required, in order to predictably obtain a product comprising the retinol in a preserved state. It should be noted that the claims do not limit the timing of when the carnosic acid is added to the medium.
It would have been obvious at the time of filling for a person of ordinary skill in the art to have arrived at the claimed invention by combining the teachings of Yu and Maiza, because both references teach the use of compositions comprising retinol for skincare applications. One would have recognized from Maiza’s disclosure that polyphenols derived from rosemary, particularly carnosic acid, may be useful in preserving retinol due to its antioxidants effects. One would have also recognized that Yu teaches the use of oils in a culture medium to bio-produce retinol, while Maiza teaches the solution of using rosemary-derived polyphenols to stabilize the lipid oxidation of retinol in oily compositions. One would have been particularly motivated to combine these teachings, because Yu teaches an improved method for producing retinol, while Maiza teaches an effective means to overcome the limited shelf-life of compositions containing retinol. As the microorganism of Yu’s disclosure produces retinol in a culture medium, it would have been obvious in view of Maiza to have added carnosic acid to the medium at a later stage of the process to protect the retinol from oxidation. As Maiza teaches carnosic acid is the major phenolic compound of rosemary extract, which was demonstrated to increase retinol content in the samples of Maiza’s study, a person of ordinary skill would have recognized the results of the combination to be predictable with a reasonable expectation of success. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Regarding claim 2, Yu teaches the method of producing retinol by culturing a microorganism in a culture medium comprising oils, as discussed above. As Maiza teaches carnosic acid to effectively preserve retinol by preventing oxidation, it would have been obvious to have added the carnosic acid to the culture medium at any time to preserve the retinol being produced. Hence, claim 2 is obvious for the same reasons discussed regarding claim 1.
Regarding claim 3, Yu teaches a method to produce retinol by culturing a microorganism that produces retinol. Hence, it would have been obvious to have added carnosic acid in an amount that is not toxic to the microorganism, because the microorganism is required to produce the retinol.
Regarding claim 4, Yu teaches the method may further include the step of recovering retinol from the cultured microorganism or culture medium using an appropriate method known in the art, and the step of recovering retinol may further include a separation process and/or a purification step (see pg. 7, para. [0081]). Furthermore, Maiza teaches retinol is a fat soluble vitamin, and carnosic acid prevents oxidation of retinol, as discussed above. Hence, it would have been obvious to isolate the composition comprising retinol from the cultured microorganism and/or culture medium while retaining the oil and the carnosic acid.
Regarding claim 5, Maiza teaches the carnosic acid in the form of a rosemary extract, as discussed above. In view of the instant specification (see pg. 2, lines 20-22) and the instant claims (e.g., claim 6), rosemary extract meets the limitation of an extract obtained from at least one plant selected from the Lamiaceae family.
Regarding claim 6, Maiza teaches that the major compound present in all samples analyzed was carnosic acid with levels ranging from 30 to 77 mg/kg (see pg. 8914, col. 1, para. 2) and, specifically, 77.1 mg/kg in the sample using rosemary extract (see pg. 8914, Table 4).
Maiza does not specifically teach an extract obtained or obtainable from rosemary with a carnosic acid content of at least about 20% by weight of the rosemary extract.
However, under the broadest reasonable interpretation of the claim, the further limitation of “wherein… the carnosic acid content in the rosemary extract…is at least about 20% by weight of the rosemary extract” does not specify the amount of carnosic added or rosemary extract added to the culture medium or the final concentration of carnosic acid in the culture medium. This limitation merely states the concentration of carnosic acid in the extract before any addition to the culture medium is made. Accordingly, it would have been prima facie obvious to have added rosemary extract of any carnosic acid concentration to the culture medium to achieve the final concentration taught by Maiza.
Regarding claim 7, Yu teaches the microorganism is cultured in a culture medium comprising soybean oil, as discussed regarding claim 1.
Regarding claim 8, Yu teaches the microorganism may be Yarrowia lipolytica or Saccharomyces cerevisiae (see pg. 6, para. [0064]).
Regarding claim 10, Yu teaches that retinol produced by the method may be used as a cosmetic composition (see pg. 2, para. [0019]). Furthermore, Maiza teaches that the compositions produced in the study could be useful for skincare, especially when they are enriched with natural antioxidants from rosemary (see pg. 8917, col. 1, para. 1). Hence, it would have been obvious to have provided the composition as s a cosmetic composition.
Regarding claim 11, Yu teaches that retinol produced by the method may be used as a cosmetic composition, and Maiza teaches that the compositions produced in the study could be useful for skincare, especially when they are enriched with natural antioxidants from rosemary, as discussed regarding claim 10. Hence, it would have been obvious to have incorporated the composition into a product.
Regarding claim 12, Yu teaches that retinol produced by the method may be used as a cosmetic composition, and Maiza teaches that the compositions produced in the study could be useful for skincare, especially when they are enriched with natural antioxidants from rosemary, as discussed regarding claim 10. Hence, it would have been obvious to have incorporated the composition into a cosmetic composition.
Regarding claim 13, Yu teaches a process of preparing a composition comprising retinol, the process comprising the step of culturing a microorganism capable of providing retinol in a culture medium comprising oil, as discussed regarding claim 1. Maiza teaches that rosemary extracts containing high carnosic acid content provide antioxidant effects to fat-soluble vitamins, such as vitamin A (i.e., retinol), and suggests that the retinol content of oily compositions can be significantly enhanced and preserved in the presence polyphenols, particularly carnosic acid, derived from rosemary, as discussed regarding claim 1. Hence, claim 13 is obvious for the same reasons as claim 1.
Regarding claim 14, Maiza teaches carnosic acid is present within an extract obtained from rosemary, as discussed regarding claim 1.
Regarding claim 15, Maiza teaches carnosic acid is present within an extract obtained from rosemary, as discussed regarding claim 1. Yu discloses that the rosemary extract was obtained from dried rosemary leaves (see pg. 8911, col. 1, para. 1).
Regarding claim 16, Maiza teaches that some problems can be linked to the transfer of phenolic compounds (e.g., carnosic acid) from plants to a highly lipophilic matrix, such as butter oil (see pg. 8914, col. 2, para. 2). Maiza teaches that to solve this problem, some studies have used aqueous and ethanolic extracts of plants instead of proper plant leaves for enrichment (see pg. 8914, col. 2, para. 3). Therefore, it would have been obvious to use carnosic acid in the form of a hydro-ethanolic extract, because Maiza teaches this may solve problems associated with transferring carnosic acid into a highly lipophilic matrix (i.e., an oil).
Regarding claim 17, Maiza teaches carnosic acid in the form of an extract obtained from rosemary, as discussed regarding claim 1. Maiza teaches that using aqueous and ethanolic extracts may solve problems associated with transferring carnosic acid into highly lipophilic matrices (i.e., oils), as discussed regarding claim 16. Hence, claim 17 is obvious for the same reasons discussed regarding claims 1 and 16.
Regarding claim 18, Maiza teaches that the major compound present in all samples analyzed was carnosic acid with levels ranging from 30 to 77 mg/kg (see pg. 8914, col. 1, para. 2) and, specifically, 77.1 mg/kg in the sample using rosemary extract (see pg. 8914, Table 4).
Maiza does not explicitly teach an extract obtained or obtainable from rosemary with a carnosic acid content of at least 30% by weight of the rosemary extract.
However, under the broadest reasonable interpretation of the claim, the further limitation of “wherein the carnosic content in the extract…is at least about 30% by weight of the rosemary extract” does not specify the amount of carnosic acid or rosemary extract added to the culture medium or the final concentration of carnosic acid required in the culture medium. This limitation merely states the concentration of carnosic acid in the extract before any addition to the culture medium is made. Furthermore, as discussed under 35 USC 112(b), the term “about” can refer to any variation, and the limitation of “at least about 30%” includes any concentration of carnosic acid in the extract. Accordingly, it would have been prima facie obvious to have added rosemary extract of any carnosic acid concentration to the culture medium to achieve the final concentration taught by Maiza.
Regarding claim 19, Yu teaches that retinol produced by the method may be used as a cosmetic composition, and Maiza teaches that the compositions produced in the study could be useful for skincare, especially when they are enriched with natural antioxidants from rosemary, as discussed regarding claim 10. Hence, it would have been obvious to have provided the composition as s a cosmetic product.
Regarding claim 20, Yu teaches that the retinol composition produced by the method has the effects of preventing skin aging, improving skin elasticity, and improving wrinkles (see pg. 2, para. [0019]) which meets the limitation of an “anti-aging product”. Hence, it would have been obvious to have provided the composition as an anti-aging product.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Yu and Maiza, as applied to claims 1-8 and 10-20 above, and further in view of Kim et al. (US Patent No. 9,644,217; previously cited), hereafter “Kim”.
Regarding claim 9, Yu does not explicitly teach the process is conducted in a bioreactor containing an aqueous phase and an oily extraction phase.
However, Yu teaches that “culturing” refers to growing the microorganism in an appropriately controlled environment, and the culture process may be achieved according to the appropriate culture conditions known in the art. Further, Yu teaches that the step of culturing the microorganism may be performed by a known batch culture method, continuous culture method, fed-batch culture method, etc. See pg. 6, para. [0067]. Yu also teaches that oxygen, nitrogen hydrogen, or carbon dioxide gas may be injected into the culture and provides ranges for aeration rates (see pg. 6, para. [0069]), culture temperatures (para. [0070]), and agitation rates for operation in a “reactor” during culturing (para. [0071]). Hence, it would have been recognized by a person of ordinary skill in the art that the culturing of the microorganism under such controlled conditions in a “reactor” could be accomplished in a “bioreactor” in view of Yu’s disclosure.
Furthermore, Kim teaches a method for producing retinoid from a microorganism, and more specifically, to a method for effectively obtaining retinoid, which lacks stability, from a microorganism by cultivating the microorganism capable of producing retinoid in a medium containing a lipophilic substance, and separating the retinoid from the lipophilic substance (see Abstract). Kim teaches that “retinoids” include retinol (see col. 4, lines 52-56). Kim teaches that retinoids are chemically unstable, easily oxidized, and liable to intracellular oxidative degradation (see col. 1, lines 56-61; col. 7, lines 50-53). Kim teaches the lipophilic substance may include dodecane and/or mineral oil (see col. 6, lines 15-19) and the culturing can take place in a “fermentation tank” (see col. 6, line 40). Kim teaches the culturing may be performed in a culture medium in the presence of a lipophilic substance while placing a dodecane phase formed of a lipophilic substance on the surface of the medium, optionally while the culture is under agitation (see col. 7, lines 24-28). Kim teaches that when a microorganism for producing retinoids is cultured without the lipophilic substance, the production of retinoids may reach a maximum level, and subsequently decrease (see col. 7, lines 46-49), whereas if the microorganism is cultured in the presence of the lipophilic substance, the produced retinoid may be absorbed into the lipophilic phase before being degraded by the cell, thereby improving productivity of retinoid (see col. 7, lines 54-59). Kim teaches the lipophilic substance may be hydrophobic and used for extracting the retinoid (see col. 7, lines 60-63).
In summary, Kim teaches the culturing of a retinol-producing microorganism in a 2-phase culture system wherein the retinol accumulates in a lipophilic, hydrophobic phase (i.e., oil) for later extraction of the retinol from the culture medium.
It would have been obvious at the time of filing for a person of ordinary skill in the art to have arrived at the claimed invention, because both Yu and Kim teach methods to produce retinol by culturing microorganisms. One of ordinary skill would have recognized from both references the suggestion to perform culturing in a “reactor” or “fermentation tank” wherein conditions during culturing could be controlled, and one would have further recognized from Kim the advantage of using a lipophilic, hydrophobic phase in the culture medium to capture and extract the produced retinol (i.e., an “oily extraction phase”). Further, one would have been motivated to combine these teachings, because Kim teaches that retinol is unstable and prone to degradation in the presence of the microbial cell, and the oily phase of the culture medium (e.g., dodecane and/or mineral oil) protects the retinol from degradation while providing an effective means for extraction. One would have also recognized that the oxidative instability of retinoids taught by Kim provides further motivation to apply the teachings of Maiza and to have added carnosic acid in the form of a plant extract to reduce oxidation and improve product yield. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Response to Arguments
Regarding the claim rejections under 35 USC 112(a) – Written Description, Applicant argues that with respect to microorganisms “capable of providing retinol” that the specification, and more particularly the incorporation by reference of the disclosure of US 2022/017878, provides sufficient disclosure to “allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described” (citing Enzo Biochem, Inc. v. Gen-Probe Inc.).
Applicant’s arguments have been fully considered but they are not persuasive.
Applicant’s arguments fail to address the lack of predictability in the art raised in the rejection. Applicant points out that sections of the specification and the disclosure of US 2022/017878 describe microorganisms capable of providing retinol, such as Yarrowia lipolytica or Saccharomyces cerevisiae, and methods of genetically engineering microorganisms to produce retinol. However, there is no discussion in the originally filed disclosure, or in the publication incorporated by reference, of any microorganism beyond the disclosed Yarrowia and Saccharomyces. Moreover, there is no disclosure, either in the present disclosure or in the prior art, of microorganisms capable of producing retinol in the presence of carnosic acid.
As discussed in the present rejection, there is unpredictability in the art due to the antimicrobial effects of carnosic acid, particularly against bacteria and fungi. However, Applicant’s Examples do not demonstrate the ability of any microorganism capable of being cultured under the recited conditions, and the specification does not provide any guidance which would allow one to envisage which microorganisms would be resistant to these effects. As acknowledged by Applicant on page 10, first paragraph of the Remarks filed 02/19/26, the scope of the claimed invention includes the “process in which the carnosic acid is already present in the culturing medium during the synthesis of the retinol by the microorganism”.
Regarding the rejections under 35 U.S.C. 103, Applicant argues that Maiza does not overcome the shortcomings of Yu, because Maiza is clearly directed to the use of natural materials, such as rosemary or clove, as antioxidants to stabilize the retinol in ghee. No skilled artisan would consider Yu together with Maiza, as both are to different technical areas, as Maiza is concerned with ‘natural’ materials, whereas Yu is to a process for producing retinol.
Applicant’s arguments have been fully considered but they are not persuasive.
Applicant is reminded that “[a] reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). See MPEP 2123.
In the instant case, Maiza teaches the use of natural compounds, such as rosemary, as antioxidants to stabilize retinol. A person of ordinary skill would have recognized from Maiza that the retinol content of oily compositions can be significantly enhanced and preserved in the presence of polyphenols, particularly carnosic acid, derived from rosemary. A person of skill would have recognized that any process involving the production of retinol in an oily composition may benefit from the presence of such antioxidants, which Maiza teaches can extend the shelf life of such products. As discussed in the present rejection, the antioxidant effects of these “natural materials” are due to the presence of phenolic compounds, the predominant one being carnosic acid.
Applicant further argues that even if Yu and Maiza were combined, one would not arrive at the process of the present invention. If Maiza was applied to the process of Yu, the rosemary/clove would be added after completion of the retinol synthesis, i.e., after the culturing step and most likely also after separating the oil and retinol mixture from the rest of the culturing medium (i.e., the aqueous phase). In contradistinction, the present invention relates to a process in which the carnosic acid is already present in the culturing medium during the synthesis of the retinol by the microorganism. Applicant alleges that the prior art combination uses hindsight reasoning (citing Sensonics, Inc. v. Aerosonic Corp.).
Applicant’s arguments have been fully considered but they are not persuasive.
First, the scope of the claims does not exclude adding carnosic acid after completion of the retinol synthesis. Here, the recitation of “wherein carnosic acid is added to the culture medium” is not recited in such a manner as to limit when the carnosic acid is added. Furthermore, in view of the specification: “The oil in the extraction phase, may comprise carnosic acid… or carnosic acid may be added to the oil at an appropriate point” (see pg. 11, lines 25-27). Therefore, the scope of the invention, as claimed, would include adding carnosic acid at any appropriate point in the claimed process in order to arrive at a final product (“composition”) comprising retinol, oil, and carnosic acid.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, the knowledge of (1) retinol production using microorganisms and (2) the antioxidative effects of carnosic acid on retinol were each known in the art at the time of filing, as disclosed by Yu and Maiza, respectively. Furthermore, Yu teaches that the culture medium comprising oil may be used in the final retinol-containing product, while Maiza discloses the beneficial antioxidant effects of including extracts of rosemary in oily compositions comprising retinol, as discussed in the present rejection.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/DENNIS IGNATIUS ARMATO JR/Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651
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