DETAILED ACTION
Objections and rejections raised in prior Office Actions are withdrawn unless restated below.
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/22/2026 has been entered.
Claim Interpretation
In view of the specification, a weight percentage of EPA, DHA and ARA is understood to include such fatty acids esterified as glycerides and not only free fatty acids. As used throughout this action, TAG is an abbreviation for triacylglycerol, which is the same as triacylglyceride.
Specification, para. [0156], provides: “A microbial oil of the invention can be any oil derived from a microorganism, including, for example: a crude oil extracted from the biomass of the microorganism without further processing; a refined oil that is obtained by treating a crude microbial oil with further processing steps such as refining, bleaching, and/or deodorizing; a diluted microbial oil obtained by diluting a crude or refined microbial oil; or an enriched oil that is obtained, for example, by treating a crude or refined microbial oil with further methods of purification to increase the concentration of a fatty acid (such as DHA) in the oil.” As such, there is not limiting definition for a microbial oil and a microbial oil can be extensively modified, including by chemical processing and enrichment of certain fatty acids, and still be a microbial oil. More specifically, an oil produced from a microbe that is further modified enzymatically and/or partially or completely purified is within the scope of a microbial oil as recited, and a TAG fraction isolated from a microbial oil is itself a microbial oil.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claim 67-96 (all pending claims) is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Apt et al. (U.S. 2010/0239533 A1) further in view of Volkman (Sterols in microorganisms, Appl Microbial Biotechnol 60, 2003, 495-506), Pirronen et al. (Plant sterols: biosynthesis, biological function and their importance to human nutrition, J. Sci. Food, Agricul. 80, 2000, 939-66), Kralovec et al. (WO 2009/040676 A2) and Singh et al. (Docosahexaenoic acid (DHA) production by Thraustochytrium sp. ATCC 20892, World J. Microbiol. Biotechnol. 17, 1996, 76-81).
Apt, abstract, states:
The present invention is directed to isolated thraustochytrid microorganisms as well as strains and mutants thereof. The invention is further directed to biomasses, microbial oils, compositions, cultures, methods of producing microbial oils, and methods of using the isolated thraustochytrids, biomasses, and microbial oils.
“Polyunsaturated fatty acids (PUFAs) are classified based on the position of the first double bond from the methyl end of the fatty acid: omega-3 (n-3) fatty acids contain a first double bond at the third carbon, while omega-6 (n-6) fatty acids contain a first double bond at the sixth carbon. For example, docosahexaenoic acid (“DHA”) is an omega-3 long chain polyunsaturated fatty acid (LC-PUFA) with a chain length of 22 carbons and 6 double bonds, often designated as “22:6 n-3.” Other omega-3 LC-PUFAs include eicosapentaenoic acid (“EPA”), designated as “20:5 n-3,” and omega-3 docosapentaenoic acid (“DPA n-3”), designated as “22:5 n-3.” DHA and EPA have been termed “essential” fatty acids. Omega-6 LC-PUFAs include arachidonic acid (“ARA”), designated as “20:4 n-6,” and omega-6 docosapentaenoic acid (“DPA n-6”), designated as “22:5 n-6.” Apt, para. [0006].
“The present invention is also directed to an isolated thraustochytrid microorganism, or a strain derived therefrom, comprising a triglyceride fraction, wherein the docosahexaenoic acid content of the triglyceride fraction is at least about 40% by weight.” Apt, para. [0012].
“The lipid classes present in the microbial oil, such as the triglyceride fraction, can be separated by flash chromatography and analyzed by thin layer chromatography (TLC), or separated and analyzed by other methods know in the art.” Apt, para. [0057]. “Flash Chromatography—Flash chromatography was used to separate the lipid classes present in the crude oils, and to determine the weight percent of each class present in the oils.” Apt, para. [0117].
“ATCC 20890—The lipid content of the ATCC 20890 biomass was estimated to be 9.2% as the sum of FAME, and the amount of crude oil obtained after solvent extraction was 10.2% by weight, giving a 111% recovery of fat present in the biomass. The EPA and DHA content of the biomass was determined to be 12.2 mg/g and 36.6 mg/g, respectively. The extracted crude oil contained 64.7 mg/g EPA and 194.2 mg/g DHA. The isolated TAG contained 41.9 mg/g EPA and 230.2 mg/g DHA, while the isolated PL contained 54.4 mg/g EPA and 149.5 mg/g DHA. The total fatty acid profiles of the biomass, extracted crude oil, TAG fraction, and PL fraction are shown below in Table 24 and Table 25 calculated as mg/g and % FAME, respectively.” Apt, para. [0148]. Table 25 shows the following composition for the isolated TAG fraction:
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Singh, Table 1, evidences that ATC 20890 is a species of Thraustochytrium, which is a thraustochytrid.
The presentation of concentrations on Table 24 of Apt in mg/g units indicates that percentages on Table 25 are weight percentages. The isolated TAG fraction of ATCC 20890 in Table 25 is a microbial oil from a thraustochytrid (Thraustochytrium) having 4.9% by weight ARA (C20:N6), 5.7% by weight EPA (C20:5 N3) and 31% by weight DHA (C22:6 N3).
“The present invention is also directed to a food product, cosmetic, or pharmaceutical composition for animals or humans comprising any one of the thraustochytrid microorganisms or biomasses of the invention or mixtures thereof.” Apt, para. [0022]. That is, the microbial oils of Apt are taught to be useful for dietary use.
Regarding recitation in the claims of a sterol fraction from 0.3 to 5% by weight in the claims, the one or more fractions isolated from the thraustochytrid includes the total fatty acid fraction, the sterol esters fraction, the triglyceride fraction, the free fatty acid fraction, the sterol fraction, the diglyceride fraction, the polar fraction (including the phospholipid fraction), and combinations thereof.” Apt, para. [0045]. “The one or more fractions isolated from the thraustochytrid includes the total fatty acid fraction, the sterol esters fraction, the triglyceride fraction, the free fatty acid fraction, the sterol fraction, the diglyceride fraction, the polar fraction (including the phospholipid fraction), and combinations thereof. . . . In some embodiments, the microbial oil comprises a triglyceride fraction of from about 65% to about 95%, about 75% to about 95%, or about 80% to about 95% by weight, or about 97% by weight, or about 98% by weight” Apt, para. [0057].
As such, Apt suggests making “combinations” of isolated fractions can be in combination and that any embodiment microbial oil would not be more than 5% while being up to 98% the TAG fraction. That is, Apt suggests that a microbial oil in general can contain sterols.
Further, Volkman reviews the production of sterols by microalgae.
“The sterols produced by higher plants have found several applications in recent years which might provide a guide to possible niche markets for sterols derived from microorganisms. These include precursors for steroid production . . . , nutraceuticals and food additives for health benefits and as natural surfactants.” Volkman, page 502, left col.
“In recent years it has become common to add plant sterols (phytosterols) as their fatty acid esters to vegetable oil table margarines at levels of approximately 8% to reduce blood cholesterol levels in consumers through their diet . . . The sterols are usually reduced to the stanols (sterols saturated at C-5) since these are equally effective in lowering plasma cholesterol and do not cause an increase in plasma levels unlike the sterols which can be detected in plasma. (Piironen et al. 2000). Microalgae might provide an alternative source of sterols for such applications.” Volkman, page 503, left col.
Piironen is briefly discussed since it is directly cited by Volkman. “The nutritional interest [of sterols] derives from the fact that the sterols have a similar structure to cholesterol, and have the capacity to lower plasma cholesterol and LDL cholesterol.” Piironen, abstract. “The usual human diet contains currently around 200-300 mg day-1 of plant sterols. The higher the dietary intake of plant sterols from the diet, the lower is the serum cholesterol level. Pirronen, page 940, left col.
As discussed above, the microbial oils discussed are suggested for dietary purposes. As far as Volkman teaches that it is beneficial to add sterols or sterol esters from microalgae to margarine (a fat/oil composition for dietary use) to benefit blood cholesterol levels of consumers through diet (in substitution of plant sterols that are further known to reduce cholesterol levels) and in view of the teachings of Apt that a microbial oil can contain a fraction of sterols, an ordinarily skilled artisan at time of filing or invention would have added sterols derived from microalgae to any microbial oil for dietary purposes taught or suggest in the prior art as discussed here in order to achieve the same benefit, which includes lowering of cholesterol levels when applied for dietary purposes.
Regarding further recitation in independent claims 67, 77 and 87 of 0.3% to 5% by weight of microbial oil being a sterol fraction and claim 74 reciting 0.3-2% by weight being a sterol fraction, Apt, para. [0057], teaches that it is known and common for such microbial oils to contain a sterol fraction including 0.5% by weight such that it would have been obvious at time of filing or invention for the microbial oil of the reference claims to be consistent with the same.
However, the microbial oil being an isolated TAG composition does not meet the specific weight percentages for EPA, DHA and ARA recite in independent claims 67, 77 and 87.
In addition to the microbial oils of Apt, other microbial oils are taught in the prior art.
Singh teaches fatty acid production of several microbial (thraustochrytrid/Thraustochytrium) species. Singh, as in Apt, teaches that such oils can be employed for dietary use . See Sing, page 76, left col. From Singh, Table 1:
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Singh does not teach a composition of a specific TAG fraction; however, Apt as discussed teaches that it is understood that a significant amount of fatty acids produced by thraustochytrid species, including ATCC 20890, are produced in the form of TAG and that such TAG fraction can be separated by flash chromatography or other methods. Singh teaches that microbial oils intended for dietary use can vary significantly in unsaturated fatty acid content. In Table 1 of Singh, for example, DHA (22:6) ranges from zero to 35% w/w with significant variation in C16:0 content. Table 1 similarly shows that ARA (C20:4) ranges from none to 3.2%. Tables 4 and 5 of Singh teach that growth media composition and temperature of growth also have a dramatic effect of fatty acid composition. The ATCC 20890 fatty acid composition reported by Singh differs significantly from Apt as reviewed above.
Kralovec, abstract, teaches:
The disclosed subject matter relates generally to a method for modifying oil, and specifically to a process for increasing the concentration of polyunsaturated fatty acid in an oil composition.
“Polyunsaturated fatty acids, such as, for example omega-3 fatty acids, are often derived from marine oils, microbial, and/or algal oils. Such sources typically provide the PUFA in a triglyceride form where other undesired, fatty acids (e.g., saturated fatty acids) are present along side a desired PUFA in the triglyceride molecule. Thus, purifying and concentrating PUFA's in a triglyceride form is generally desired.” Kralovec, page 2, ln. 4-8.
“Disclosed herein is a method for removing at least a portion of a saturated and/or short chain fatty acid fraction of an oil composition comprising, for example, a glyceride, and esterifying at least a fraction of a PUFA to form a substituted triglyceride. In one aspect, the method can provide an oil having higher levels of a PUFA, such as, for example, EPA, DHA, or a combination thereof, than the starting oil composition. In a specific aspect, the various methods and aspects thereof can be used to replace a saturated and/or short chain fatty acid positioned on a glyceride, such as a diglyceride and/or a triglyceride, with a polyunsaturated fatty acid, such as an EPA, DHA, or a combination thereof. The methods disclosed herein can be useful in, for example, hydrolyzing one or more saturated fatty acids from a starting glyceride using a lipase enzyme, and then removing the saturated fatty acids. The remaining glyceride (that is, the hydrolyzed glyceride) can then be esterified with one or more polyunsaturated fatty acids to provide a final glyceride product having a higher concentration in polyunsaturated fatty acids than the starting material. In one example, the one or more fatty acids hydrolyzed from a starting glyceride comprise at least one saturated or short chain fatty acid. In another example, the one or more polyunsaturated fatty acids comprise EPA, DHA, or a combination thereof. Depending upon the starting oil, glyceride, reaction conditions, and polyunsaturated fatty acid(s), the specific composition of a treated oil (e.g., glyceride) can be adjusted and/or tailored to have a target ratio of various polyunsaturated fatty acids. Such tailored compositions can be useful, for example, in providing glycerides that comprise high concentrations of DHA that exhibit greater oxidation resistance.“ Kralovec, pages 5-6.
Examples 2-4 of Kralovec provides an exemplary embodiment wherein a series of microbial oil samples were hydrolyzed to remove at least a fraction of a fatty acid and esterified with “one of three different high EPA or DHA concentrated free fatty acids (FFA): FFA20/48, FFA24/54 and FFA55/16 (EPA/DHA), respectively.” Kralovec, page 40, ln. 4-5.
Table 9.1 of Kralovec shows a starting microbial oil having 35.4% 16:0 fatty acid, 0.6% C20:5 fatty acid (EPA) and 22% C22:6 fatty acid (DHA) is modified after hydrolysis and re-esterification with FFA55/16 (EPA/DHA) to 17.3%, 12.4% and 34.5%, respectively. It is noted that the increase from 0.6% to 12.4% for EPA is a 20-fold increase in EPA content, and DHA content is also significantly increased.
Table 9.2 of Kralovec reproduced below indicates that the starting microbial oil is 100% TG (triacylglyceride) but only 91.2% glyceride after undergoing the above process.
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Both Apt and Kralovec relate to microbial oils for dietary use.“ “The present invention is also directed to a food product, cosmetic, or pharmaceutical composition for animals or humans comprising any one of the thraustochytrid microorganisms or biomasses of the invention or mixtures thereof.” Apt, para. [0022]. “Diets rich in PUFA's like omega-3 fatty acids have also been shown to have beneficial effects for heart disease, cancer, arthritis, allergies, and other chronic diseases.” “Further oils include, microbial oil, algal oil (e.g., oil from a dinoflagellate such as Crypthecodinium cohnii), fungal oil (e.g., oil from Thraustochytrium, Schizochytrium, or a mixture thereof).” Apt, page 1, ln. 27-29, and page 7, ln. 18-21).
“Compositions prepared by the disclosed methods are also contemplated. By the methods disclosed herein, concentrated oils with triglycerides containing higher proportions of polyunsaturated fatty acid esters than the starting glycerides can be produced. For example, the disclosed compositions can comprise triglycerides with higher DHA or balanced DHA/EPA contents than the starting triglycerides. Further, "designer" glycerides having specifically designed, and often non-naturally occurring, ratios of polyunsaturated fatty acid ester can be prepared.” Kralovec, page 35, ln. 21-27.
“The disclosed oils can also have a high TG (triglyceride) content. For example, the
oil can comprise greater than or equal to about 60%, 65%, 70%, 75%, or 80% TG by
weight of the total composition, where any of the stated values can form an upper or lower
endpoint of a range. For example, the disclosed oil can comprise from about 60% to about
80%, from about 70% to about 80%, from about 65% to about 75% TG by weight of the
total compositions.” Kralovec, page 37, ln. 22-27.
“In other examples, disclosed are oils that comprise greater than or equal to about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, or 80% DHA by weight of the total composition, where any
of the stated values can form an upper or lower endpoint of a range. For example, the
disclosed oils can comprise from about 40% to about 90%, from about 50% to about 90%,
from about 60% to about 90%, from about 70% to about 90%, from about 80% to about
90%, from about 40% to about 80%, from about 40% to about 70%, from about 40% to
about 60%, from about 40% to about 50%, from about 50% to about 80%, or from about
60% to about 70% DHA by weight of the total composition.” Kralovec, page 36, ln. 12-20.
In summary, Kralovec teaches a method for enriching the amount of EPA or DHA in an oil as follows as in Fig. 1:
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That is, Kralovec teaches that for any microbial oil for the purpose of dietary use:
1) It is advantageous to treat the same as taught by Kralovec to reduce the presence of saturated fatty acids; and
2) The treatment for purpose of reducing saturated fatty acids is demonstrate to significantly increase EPA as shown in Table 9.1 of Kralovec as well as to increase DHA.
While Kralovec in the working examples employs a mixture of EPA and DHA for re-esterification, Kralovec explicitly teaches “the various methods and aspects thereof can be used to replace a saturated and/or short chain fatty acid positioned on a glyceride, such as a diglyceride and/or a triglyceride, with a polyunsaturated fatty acid, such as an EPA, DHA, or a combination thereof.” This is understood as an explicit teaching that EPA only can be used to replace saturated fatty acid rather than a combination of EPA and DHA wherein the amount of DHA present in the treated oil will not increase significantly. Or in the alternative, a ratio of EPA and DHA employed for esterification is not restricted.
As such, at the time of the invention or filing, an ordinarily skilled artisan would have been motivated to subject any microbial oil containing 100% or nearly pure triacylglycerol (TAG) to the methods of Kralovec in order to achieve the benefit of reduced saturated fatty acid content expressly taught by Kralovec to be beneficial for such oils to be used for dietary use. Such microbial oils include:
Microbial Oil from Tables 9.1 and 9.2 of Kralovec being 100% TAG and 35.4% 16:0 fatty acid, 0.6% C20:5 fatty acid (EPA) and 22% C22:6 fatty acid (DHA); and
Any of the microbial oils taught by Singh,
including a TAG fraction of microbial oil isolated by flash chromatography from any of these microbial oils.
It is noted that the percentages reported by Kralovec are reported in terms of “area %” as measured by a detector rather than in units of percent by weight of composition. However, only broad ranges are recited in the claims rather than specific values. “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). MPEP 2144.05(II)(A). It is noted that any fatty acid content of an oil being an embodiment of the claims necessarily has a concentration measurable in terms of percent by weight of composition.
Further, as discussed, Kralovec expressly teaches that saturated fatty acid can be replaced by re-esterification by EPA and/or DHA such that an ordinarily skilled artisan at the time of filing or invention would have been motivated to follow the express instruction of Kralovec that saturated fatty acid (such as C16:0 fatty acid) be replaced with EPA only (rather than a mixture of EPA and DHA). As such, applying the re-esterification method of Kralovec with EPA only to either of oils:
Isolated TAG fraction of ATCC 20890 is a microbial oil from a thraustochytrid having 28.0% C16:0 fatty acid by weight, 4.9% by weight ARA (C20:N6), 5.7% by weight EPA (C20:5 N3) and 31% by weight DHA (C22:6 N3) as taught by Apt (Table 25) as above, or
Microbial Oil from Tables 9.1 and 9.2 of Kralovec being 100% TAG and 35.4% 16:0 fatty acid, 0.6% C20:5 fatty acid (EPA) and 22% C22:6 fatty acid (DHA), and 0.9% C20:4 fatty acid (ARA),
results in an oil with similar composition but with increased EPA content and reduced 16:0 fatty acid content. “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." As such, it is not inventive to perform re-esterification on any of the above oils in a manner, for example, wherein the 5.7% by weight percentage of EPA in the ATCC 20890 TAG is increased to a value of 20%, 25% or 35% wherein, as discussed, Kralovec teaches ability to significantly increase EPA content. While Kralovec does not report concentration in terms of weight percent, area under the curve approximates weight percent wherein an increase of EPA content by reduction of C16:0 would be expected to fall within the recited range of 20-45% by weight (or at least 20% by weight ) EPA.
Performing an increase of EPA content to the TAG fraction of Microbial Oil from Tables 9.1 and 9.2 of Kralovec, to for example 20%, with minimal or no change in DHA and ARA content (22% and 0.9%, respectively), wherein 20% by weight EPA is 20%/(20%EPA+22%DHA)=45% amount of EPA of total amount of EPA and DHA. Kralovec, Table 9.1, teaches that when an oil that is 100% TAG is subjected to the hydrolysis and re-esterification described that a composition that is about 90% TAG or within the range 65%-98% TAG (or any further recited subranges in the claims) of the overall composition is expected. Further, EPA and DHA are the only significant omega-3 fatty acid species present as to be over 90% of omega-3 fatty acids present.
Claim 67 and claims depending therefrom recite EPA, DHA and ARA content as a percent total weight of the microbial oil. Claim 77 and claims depending therefrom recite EPA, DHA and ARA content as a percent total weight of the TAG fraction specifically. Claim 87 recites EPA and ARA as a percent of the microbial oil and DHA as a percent of TAG fraction, wherein dependent claim 93 recites DHA as a percent of total weigh of microbial oil. It is noted the claims recite the following ranges:
EPA: 20-45%, 25-35% (claim 90), 30-40% (claim 91), 25-40%, 30-45% by weight based on total weight of microbial oil;
EPA: at least 20%, 25-40% and 30-45% by weight of triacylglycerol (TAG) fraction;
DHA: 10-30%,10-25% and 15-25% (claim 93) by weight based on total weight of microbial oil;
DHA: 10-30% and 10-25% by weight of triacylglycerol (TAG) fraction;
ARA: 0.1-5% by weight based on total weight of microbial oil; and
ARA: 5% or less by weight of triacylglycerol (TAG) fraction.
As discussed above, Kralovec teaches that when an isolated TAG fraction is subjected to re-esterification as taught therein, the resulting microbial oil is expected to be about 90% TAG or to otherwise fall within the range of TAG fraction recited in claims 67, 68, 77, 78, 87, 88 and 89. As such, presence of specific fatty acids in terms of by weight based on total weight of microbial oil or by weight of triacylglycerol (TAG) fraction will be similar for a composition that is about 90% TAG fraction such that the prior art teaching or suggesting a fatty acid present in a concentration expressed as terms of by weight based on total weight of microbial oil is also understood to suggest a similar numerical range in terms of triacylglycerol (TAG) fraction, and vice versa. Stated in other words, all claims recite broad ranges for concentration of EPA, DHA and ARA wherein “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." Here, as discussed, Kralovec discuss the general conditions of increasing concentration of EPA and/or DHA with corresponding decrease in saturated fatty acid by hydrolysis and re-esterification such that it is not inventive to discover specific workable concentrations of EPA, DHA and or ARA whether expressed in units of percent weight of total microbial oil or percent weight of a TAG fraction.
Further, the prior art of Apt, Kralovec and Singh evidence that oils vary significantly in composition. This is further evidenced by Singh teaching fatty acid production of several microbial (thraustochytrid) species.
As discussed, Apt teaches that a TAG fraction can be isolated by chromatography. In conformation with Kralovec and Apt, Singh teaches that microbial oils intended for dietary use can vary significantly in unsaturated fatty acid content. In Table 1 of Singh, for example, DHA (22:6) ranges from zero to 35% w/w with significant variation in C16:0 content. Table 1 similarly shows that ARA (C20:4) ranges from none to 3.2%. Tables 4 and 5 of Singh teach that growth media composition and temperature of growth also have a dramatic effect of fatty acid composition. The ATCC 20890 fatty acid composition reported by Singh differs significantly from Apt.
“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). MPEP 2144.05(II)(A).
The general conditions of the prior art is that microbial oils from Thraustochytrium and Schizochytrium species vary widely in their unsaturated fatty acid content including DHA. The cited prior art, including Sing, teach that DHA content in particularly may run from zero to 52% w/w (see Table 4, Singh, Sodium glutamate nitrogen source) for total fatty acid present where the percent w/w in any isolated TAG fraction thereof would have a similar range of diversity. In view of this, it is not inventive to start with an isolated Thraustochytrium or Schizochytrium oil that can have 20%, 30%, 35% or 45% DHA or EPA, and further including an amount of ARA in a range of 0.1-5% (ex. 2.7 or 3.2% as in Table 1 of Singh) and treat the same to replace C16:0 with EPA by the methods of Kralovec to arrive at an oil with, for example, about 20%, 25%, or 30% of both EPA and DHA particularly wherein Kralovec teaches the disclosed compositions can comprise triglycerides with higher DHA or balanced DHA/EPA contents than the starting triglycerides, or in the alternative having EPA being 45% by weight of a TAG fraction (claim 83) with a corresponding, for example, 30% DHA by weight of a TAG fraction (which is 60% EPA by weigh of total amount of EPA and DHA in implementations wherein the composition of TAG fraction and overall microbial oil is similar).
Kralovec, page 36, lines 12-15, teaches “In other examples, disclosed are oils that comprise greater than or equal to about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, or 80% DHA by weight of the total composition, where any of the stated values can form an upper or lower endpoint of a range.” But as discussed, Kralovec, Table 9.1, teaches a microbial oil with 34.5% DHA, and in Table 8.2 a microbial oil with 54.2% DHA. Kralovec further teaches non-microbial oils including a fish oil in Example 6 to have 16.8% DHA in Table 12. As such, Kralovec is understood as teaching a wide range of DHA is envisioned including scenarios wherein the amount of DHA and EPA is balanced or similar.
An isolated TAG treated by methods of Kralovec to have, for example, 20%, 25% or 30% w/w of both DHA and EPA as either weight percent of total fatty acid or TAG fraction has EPA being 50% by weight of total amount of EPA and DHA as meeting the corresponding ranges recited in the claims (wherein composition of TAG fraction and overall microbial oil is expected to be similar), and further meets the ranges of EPA and DHA based on total weight of microbial oil and/or weight of TAG fraction as recited and reviewed above. As discussed, any isolated TAG fraction subjected to the methods of Kralovec is expected to have about 90% TAG including a minor portion of free fatty acid acids expected to fall within the range of 0.5% to 5% (see Kralovec, Table 9.2).
Regarding claims 73 and 84, the limitations of these claims are met if one of the recited fatty acids is less than 5%. As can be seen in Table 25 of Apt shows that microbial oils having no C18:3 (N3) (i.e. 18:3n-3 fatty acid). As such, formation of microbial oils satisfying the features of claims 73 and 84 (regarding fatty acids directly recited in those claims) is suggested by Apt.
It is further noted that claims 77-84 all recite ranges of EPA, DHA and ARA concentration including EPA and DHA being 90% or more of omega-3 fatty acids and EPA being a percentage of total EPA and DHA with relation to weight percentage or presence in a TAG fraction of an embodiment microbial oil. Kralovec teaches the disclosed compositions can comprise triglycerides with higher DHA or balanced DHA/EPA contents such that the above discussion applies specifically to TAG fraction with such balanced DHA/EPA content as well as for any overall microbial oil composition, where, as discussed, such balanced DHA/EPA content can be 20%, 25%, 30% or 35% as total weight of microbial oil or of the TAG fraction, or as discussed, 45% of EPA with a corresponding amount (e.g. 25% DHA), whether expressed as percent weight of total oil or a TAG fraction.
Regarding 0.1% to 5% by weight of ARA based upon microbial oil or 5% or less by weight of triacylglycerol (TAG) fraction, several of the oils taught by Kralovec, Apt and Singh have ARA falling within such range including 4.9% in Table 25 of Apt and the following value in Table 1 of Singh:
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As such, the prior art directly teaches that microbial oils containing a minor amount of ARA falling within the recited ranges of 0.1% to 5% by weight of ARA based upon microbial oil or 5% or less by weight of triacylglycerol (TAG) fraction is an expected and common amount of ARA to be found in a Schizochytrium or Thraustochytrium microbial oil. “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). MPEP 2144.05(II)(A).
Regarding claim 96, a “composition of the invention can include one or more excipients.” Apt, para. [0064]. As such, Apt directly teaches that any microbial oil consistent with the teachings thereof can advantageously be combined with an excipient for form a composition such that an ordinarily skilled artisan at time of filing or invention would have been motivated to do the same.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 67-96 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more. The claim(s) recite(s) a microbial oil being a mixture of various naturally-occurring compounds. This judicial exception is not integrated into a practical application because the claims recite no features that can be considered to be a practical application. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not recite any additional elements except for the natural product exception.
MPEP 2106(III) directs that claims drawn to 1) a composition of matter (step 1), 2) a law of nature or a natural phenomenon or a product of nature (step 2A) and 3) lacking recitation of additional elements that make the claims directed to significantly more than a judicial exception (step 2B) are ineligible for patenting under 35 U.S.C. 101. See MPEP 2106(III), flow chart. Step 2A into two prongs as set forth in MPEP 2106.04(II)(A).
“If the claim includes a nature-based product that does not exhibit markedly different characteristics from its naturally occurring counterpart in its natural state, then the claim recites a "product of nature" exception, and requires further analysis in Step 2A Prong Two to determine whether the claim as a whole integrates the exception into a practical application.” MPEP 2106.04(c). “It is important to keep in mind that product of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart.” MPEP 2106.04(b)(II).
“The markedly different characteristics analysis is part of Step 2A Prong One, because the courts use this analysis to identify product of nature exceptions.” MPEP 2106.04(c). “The markedly different characteristics analysis compares the nature-based product limitation to its naturally occurring counterpart in its natural state. Markedly different characteristics can be expressed as the product’s structure, function, and/or other properties, and are evaluated based on what is recited in the claim on a case-by-case basis. If the analysis indicates that a nature-based product limitation does not exhibit markedly different characteristics, then that limitation is a product of nature exception. If the analysis indicates that a nature-based product limitation does have markedly different characteristics, then that limitation is not a product of nature exception.” MPEP 2106.04(c)(II).
Examiners should keep in mind that if the nature-based product limitation is naturally occurring, there is no need to perform the markedly different characteristics analysis because the limitation is by definition directed to a naturally occurring product and thus falls under the product of nature exception.” MPEP 2106.04(c)(I).
The claims are directed towards a product.
The claims recite a microbial oil. However, recitation that an oil is “microbial” is an indication only how such oil is made. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." MPEP 2113(I). Specification, para. [0156], provides: “A microbial oil of the invention can be any oil derived from a microorganism, including, for example: a crude oil extracted from the biomass of the microorganism without further processing; a refined oil that is obtained by treating a crude microbial oil with further processing steps such as refining, bleaching, and/or deodorizing; a diluted microbial oil obtained by diluting a crude or refined microbial oil; or an enriched oil that is obtained, for example, by treating a crude or refined microbial oil with further methods of purification to increase the concentration of a fatty acid (such as DHA) in the oil.” As such, there is no limiting definition for a microbial oil and a microbial oil can be extensively modified, including by chemical processing and enrichment of certain fatty acids, and still be a microbial oil.
“In Myriad, the Supreme Court made clear that not all changes in characteristics will rise to the level of a marked difference, e.g., the incidental changes resulting from isolation of a gene sequence are not enough to make the isolated gene markedly different. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75.” MPEP 2106.04(d). “For example, assume that applicant claims a nucleic acid having a nucleotide sequence derived from naturally occurring gene B. Although gene B occurs in nature as part of a chromosome, the closest natural counterpart for the claimed nucleic acid is gene B, and not the whole chromosome.” MPEP 2106.04(c)(II)(A). Isolation or enrichment of otherwise naturally-occurring oil components is an incidental change as discussed by Myriad.
That is, isolation of a product from its natural environment, whether being a gene, protein, compound or a composition as in the recited microbial oil, is not itself a markedly different characteristic. As discussed, embodiments of the claims include oils produced by refinement or purification to increase the concentration of a fatty acid in an embodiment oil. It is further noted that the microbial oils are a mixture of different lipid compounds and as indicated above a product is not required to be made by any specific process. The specification, para. [0156], makes it clear that the recited microbial oil need not be made directly by a microbial species but can be the subject of extensive modification.
“It is important to keep in mind that product of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart.” MPEP 2106.04(II).
Apt et al. (U.S. 2010/0239533 A1), similar to the current application, discusses microbial oils produced from thraustochytrid species. Table 9 of Apt discusses several TAG species isolated from such microbial oils where such individual species include specific TAG that are naturally-occurring compounds produced by the natural metabolism of thraustochytrid species. Such TAG species includes the specific TAG compounds with indicated fatty acid esterified on sn-1/sn-2/sn-3 positions: DHA/DHA/DHA, EPA/EPA/DHA, DHA/DHA/EPA, 16:0/16:0/16:0, DHA/DHA/ARA. U.S. 2010/0239533 A1, para. [0057], indicates that sterols are also naturally-occurring compounds produced by the natural metabolism of thraustochytrid species. Glycerol and free fatty acids are also naturally-occurring compounds. Fatty acid such as 18:1n-9 fatty acids and TAG containing the same are also natural products.
Embodiments of all the claims, including the various percentage weight limitations for EPA, DHA and ARA based on the total microbial oil or a TAG fraction thereof, limitations regarding EPA is from 36-65% by weight of the total EPA and DHA (and narrower ranges in dependent claims), any requirement that over 90% of omega-3 fatty acids be DHA and EPA, 0.3-5% or 0.3-2% by weight sterols, and all concentration- or ratio-related limitations of the claims can be met by mixing together such isolated fatty acid, TAG and sterol compounds as reviewed above in appropriate amounts to meet the limitations of microbial oil as recited in the claims. The evidence of record supports that every one of these TAG and generic sterol compounds is a naturally-occurring compound produced by the metabolism of at least Thraustochytrium species.
Further, microbial oils including those produced directly by Thraustochytrium species, vary broadly in fatty acid composition. Fan et al. (Eicosapentaenoic and docosahexaenoic acids production by and okara-utilizing potential of thraustochytrids, J. Industrial Microbiol. Biotechnol. 67, 2001, 199-202), in Table 2 reports fatty acid content in the biomass of various thraustochytrid species including Thraustochytrium striatum that is 36.6% DHA (C22:6) and 23.3% EPA (C20:5). Other reported thraustochytrid species vary significantly in amount of DHA, EPA and ARA (C20:4) present. Fan do not report the fatty acid composition of purified microbial oil or TAG fraction thereof. Regardless, Fan reports that naturally-occurring microbial oils vary significantly in DHA, EPA and ARA content and include oils with high amounts of EPA and ARA. Embodiment microbial oils of the claims can be made by 1) blending microbial oils from different sources together that can include either dilution or concentration (e.g. removing certain fatty compounds) to meet the various concentration requirements for DHA, EPA, ARA and sterols recited in the claims.
In Table 25 of Apt, an apparently naturally-occurring microbial oil with TAG fraction having 5.7% EPA (C20:5 N3) and 31.3% DHA (22:6 N3). An embodiment of at least claim 67 can be formed by taking this starting oil, adding an amount of purified EPA-containing TAG such that the EPA concentration is within recited range of 20-45% by weight and DHA is diluted to be within the range of 10-30% by weight and adding in the required amount of sterol and ARA and diluting with a diluent such that the TAG fraction is with the range of 65%-98%. All embodiments of the claims can be similarly made by adding components to a base microbial oil without use of all purified components. The purpose of this discussion is to highlight that the claimed microbial oil compositions read on mixtures of otherwise naturally-occurring microbial oils and components thereof.
Regarding claims 73 and 84, these claims are met simply by omitting the recited oils not to be present when forming embodiments by mixing purified TAG compounds and sterols or diluting the microbial oil to meet these features.
“Where the claim is to a nature-based product produced by combining multiple components (e.g., a claim to "a probiotic composition comprising a mixture of Lactobacillus and milk"), the markedly different characteristics analysis should be applied to the resultant nature-based combination, rather than its component parts. For instance, for the probiotic composition example, the mixture of Lactobacillus and milk should be analyzed for markedly different characteristics, rather than the Lactobacillus separately and the milk separately. See subsection II, below, for further guidance on the markedly different characteristic analysis.” MPEP 2106.04(c)(I)(A). “When the nature-based product is a combination produced from multiple components, the closest counterpart may be the individual nature-based components of the combination. For example, assume that applicant claims an inoculant comprising a mixture of bacteria from different species, e.g., some bacteria of species E and some bacteria of species F. Because there is no counterpart mixture in nature, the closest counterparts to the claimed mixture are the individual components of the mixture, i.e., each naturally occurring species by itself.” MPEP 2106.04(c)(II)(A).
The rejected claims represent a nature-based product that can be produced by combining multiple components, all such components being naturally-occurring. The combination forming embodiment microbial oils is compared to the individual nature-based components of the combination, which are various TAG, sterols, fatty acid, and other compounds discussed above. However, there is no indication that the combination has any markedly different characteristics. For example, the components react, become more stable or have any other discernable specific interaction between chemical components. In contrast, gun powder being a mixture of natural components becomes more explosive. While the microbial oil may have nutritional properties, these properties would appear to be the same as if each component was individually digested not in a mixture/combination. As such, for step 2A, prong 1, there does not appear to be a markedly different characteristic for the nature-based combination being the recited microbial as recited in all of the claims.
For step 2A, prong 2, and step 2B, the claims do not recite any additional elements nor integration into an application that would weigh in favor of subject matter eligibility. While claim 96 recites an additional generic excipient, such excipients as discussed in para. [0164] and [0175] of the specification includes antioxidants, sugars (sucrose), etc., that include compounds that themselves are naturally-occurring products. There is no evidence of record that inclusion of a further generic excipient, e.g. sucrose, results in any markedly different characteristic as to satisfy step 2A, prong 1, as discussed above. Regarding, step 2A, prong 2, “Prong Two asks does the claim recite additional elements that integrate the judicial exception into a practical application? In Prong Two, examiners evaluate whether the claim as a whole integrates the exception into a practical application of that exception.” MPEP 2106(II)(A)(2). Regarding Step 2B for the claims, “Step 2B asks: Does the claim recite additional elements that amount to significantly more than the judicial exception”? MPEP 2106.05(II). Additional recitation of a generic excipient, e.g. sucrose, does not integrate the claim into a practical application and further does not amount to more than the judicial exception wherein sucrose is itself a natural product.
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 67-96 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 67-68 and 70-84 of copending Application No. 17/519,961 in view of Apt et al. (U.S. 2010/0239533 A1).
The current application is a continuation of 17/519,961.
The reference claims recite:
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“In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.” “Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.” MPEP 2144.05(I).
The claims recite a microbial oil (contained within a biomass) that is 65% by weight of a triglyceride (TAG) fraction reciting amounts of DHA and EPA that overlap or are otherwise close to the ranges recited in the rejected claims as to establish a prima facie case of obviousness. It is noted that the claims recite concentration of DHA and EPA for the microbial oil and not specifically the TAG fraction. However, it would appear that there is a close relationship to the fatty acid content of the TAG fraction and the overall microbial oil such that an ordinarily skilled artisan at time of invention or filing would understand the recited concentrations of DHA and EPA to be applicable to a TAG fraction as well. Further, specific concentrations of DHA and EPA within these ranges satisfy the recitation of EPA is from 36-65% of total amount of EPA and DHA as to be encompassed by overlapping or close ranges being prima facie obvious.
The reference claims do not recite 0.1% to 5% by weight of ARA and other recited ranges of ARA. The teachings of Apt discussed above are incorporated herein by reference. Apt, Table 25, and related discussion in Apt teach that it is common for microbial oils from Thraustochytrid organisms to contain a minor amount of ARA falling within a range of 0.1-5%. Similarly, Apt, para. [0057], teaches that it is known and common for such microbial oils to contain a sterol fraction including 0.5% by weight such that it would have been obvious at time of filing or invention for the microbial oil of the reference claims to be consistent with the same. Further, nothing in the reference claims indicates any requirement or presence of omega-3 fatty acids other than DHA and EPA to be present as to meet the requirement that over 90% of omega-3 fatty acids present in any microbial oil or TAG fraction be DHA or EPA. Less than 5% by weight as recited in claims 73 and 84 includes zero as less than 5%. As far as the specific fatty acids recited in claims 73 and 84 are not recited in the reference claims, it would have been obvious at time of filing or invention for the same to not be present or present in low amounts less than 5% in any embodiment microbial oil or TAG fraction of the reference claims.
Regarding claim 96, a “composition of the invention can include one or more excipients.” Apt, para. [0064]. As such, Apt directly teaches that any microbial oil can advantageously be combined with an excipient for form a composition such that an ordinarily skilled artisan at time of filing or invention would have been motivated to do the same regarding any oil suggested by the reference claims.
This is a provisional nonstatutory double patenting rejection.
Claims 67-96 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,798,952 in view of Apt et al. (U.S. 2010/0239533 A1).
Claims 67-96 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 9,924,733 in view of Apt et al. (U.S. 2010/0239533 A1).
Claims 67-96 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 9,668,499 in view of Apt et al. (U.S. 2010/0239533 A1).
Claims 67-96 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11154076 in view of Apt et al. (U.S. 2010/0239533 A1).
The ‘076, ‘499, ‘952 and ‘733 patents share the same specification.
Claims of ‘499 recite:
1. A microbial oil comprising 20% to 40% by weight of eicosapentaenoic acid, at least 25% by weight of docosahexaenoic acid and less than 5% by weight of each arachidonic acid, docosapentaenoic acid n-6, docosapentaenoic acid n-3, oleic acid, linoleic acid, linolenic acid, eicosenoic acid, erucic acid, and stearidonic acid in the total of fatty acids, wherein said microbial oil is produced by an isolated strain of thraustochytrid, wherein said microbial oil further comprising an effective amount of at least one added antioxidant to provide oxidative stability.
Claims of ‘076 recite:
1. A blended oil composition comprising a vegetable oil and a microbial oil comprising a polyunsaturated fatty acids (PUFA) fraction produced from a single isolated strain of thraustochytrid microorganism, wherein said PUFA fraction comprises a triacylglycerol fraction which is at least 10% by weight of said PUFA fraction, wherein at least 12% by weight of the fatty acids in the triacylglycerol fraction is eicosapentaenoic acid (EPA), wherein at least 25% by weight of the fatty acids in the triacylglycerol fraction is docosahexaenoic acid (DHA), and wherein less than 5% by weight of the fatty acids in the triacylglycerol fraction is arachidonic acid (ARA), wherein said thraustochytrid microorganism is of the genus Schizochytrium or Thraustochytrium, and wherein said refined oil further comprises an effective amount of at least one added antioxidant to provide oxidative stability.
2. The vegetable oil of claim 1, wherein the triacylglycerol fraction is at least 40% by weight of said PUFA fraction.
3. The vegetable oil of claim 1, wherein at least 15% by weight of the fatty acids in the triacylglycerol fraction is eicosapentaenoic acid.
4. The vegetable oil of claim 1, wherein at least 35% by weight of the fatty acids in the triacylglycerol fraction is docosahexaenoic acid.
5. The vegetable oil of claim 1, wherein 2% or less by weight of the fatty acids in the triacylglycerol fraction is arachidonic acid.
Claims of ‘952 recite:
1. A biomass produced from a single isolated strain of thraustochytrid microorganism comprising a triacylglycerol fraction which is at least 60% by weight of the extracted crude oil content of said biomass, wherein from 10% to 30% by weight of the triacylglycerol fraction is eicosapentaenoic acid, wherein said thraustochytrid microorganism is of the genus Schizochytrium or Thraustochytrium, wherein said biomass further comprising an effective amount of at least one added antioxidant to provide oxidative stability.
2. The isolated biomass of claim 1, wherein the triacylglycerol fraction is between 65% to 95% by weight.
3. The isolated biomass of claim 1, wherein from 15% to 30% by weight of the fatty acids in the triacylglycerol fraction is eicosapentaenoic acid.
4. The isolated biomass of claim 1, wherein at least 25% by weight of the fatty acids in the triacylglycerol fraction is docosahexaenoic acid.
Claims of ‘733 recite:
1. A microbial oil comprising a triacylglycerol fraction which is between 75% to 98% by weight of said microbial oil, wherein between 10% to 30% by weight of the fatty acids in the triacylglycerol fraction is eicosapentaenoic acid, wherein between 30% to 50% by weight of the fatty acids in the triacylglycerol fraction is docosahexaenoic acid, and wherein less than 5% by weight of the fatty acids in the triacylglycerol fraction is arachidonic acid, wherein said microbial oil is produced by an isolated strain of thraustochytrid, wherein said microbial oil also comprising an effective amount of at least one added antioxidant to provide oxidative stability.
2. The microbial oil of claim 1, wherein said triacylglycerol fraction is triacylglycerol fraction of between 80% to 98% by weight.
3. The microbial oil of claim 2, wherein said triacylglycerol fraction is of between 90% to 98% by weight.
4. The microbial oil of claim 1, wherein between 10% to 25% by weight of the fatty acids in the triacylglycerol fraction is eicosapentaenoic acid.
5. The microbial oil of claim 4, wherein between 5% to 25% by weight of the fatty acids in the triacylglycerol fraction is eicosapentaenoic acid.
6. The microbial oil of claim 3, wherein between 10% to 20% by weight of the fatty acids in the triacylglycerol fraction is eicosapentaenoic acid.
7. The microbial oil of claim 1, wherein between 35% to 50% by weight of the fatty acids in the triacylglycerol fraction is docosahexaenoic acid.
8. The microbial oil of claim 3, wherein between 30% to 40% by weight of the fatty acids in the triacylglycerol fraction is docosahexaenoic acid.
9. The microbial oil of claim 1, wherein 3% or less by weight of the fatty acids in the triacylglycerol fraction is arachidonic acid.
10. The microbial oil claim 8, wherein 2% or less by weight of the fatty acids in the triacylglycerol fraction is arachidonic acid.
“In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.” “Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.” MPEP 2144.05(I).
The claims recite a microbial oil (contained within a biomass) or a microbial oil that is 65%-95% or 75% to 98% by weight of a triglyceride (TAG) fraction reciting amounts of DHA and EPA that overlap or are otherwise close to the ranges recited in the rejected claims as to establish a prima facie case of obviousness. In embodiments of the reference claims that are 95% or 98% by weight TAG, the concentration of any of DHA, EPA and ARA will be similar in value whether expressed as a percent by weight of a microbial oil or of a TAG fraction. It is noted that the claims recite concentration of DHA and EPA for the microbial oil and not specifically the TAG fraction. However, it would appear that there is a close relationship to the fatty acid content of the TAG fraction and the overall microbial oil such that an ordinarily skilled artisan at time of invention or filing would understand the recited concentrations of DHA and EPA to be applicable to a TAG fraction as well. Further, specific concentrations of DHA and EPA within these ranges satisfy the recitation of EPA is from 36-65% of total amount of EPA and DHA as to be encompassed by overlapping or close ranges being prima facie obvious.
The reference claims do not recite 0.1% to 5% by weight of ARA and other recited ranges of ARA. The teachings of Apt discussed above are incorporated herein by reference. Apt, Table 25, and related discussion in Apt teach that it is common for microbial oils from Thraustochytrid organisms (including Thraustochytrium) to contain a minor amount of ARA falling within a range of 0.1-5%. Similarly, Apt, para. [0057], teaches that it is known and common for such microbial oils to contain a sterol fraction including 0.5% by weight such that it would have been obvious at time of filing or invention for the microbial oil of the reference claims to be consistent with the same. Further, nothing in the reference claims indicates any requirement or presence of omega-3 fatty acids other than DHA and EPA to be present as to meet the requirement that over 90% of omega-3 fatty acids present in any microbial oil or TAG fraction be DHA or EPA. Less than 5% by weight as recited in claims 73 and 84 includes zero as less than 5%. As far as the specific fatty acids recited in claims 73 and 84 are not recited in the reference claims, it would have been obvious at time of filing or invention for the same to not be present or present in low amounts less than 5% in any embodiment microbial oil or TAG fraction of the reference claims.
Regarding claim 96, a “composition of the invention can include one or more excipients.” Apt, para. [0064]. As such, Apt directly teaches that any microbial oil can advantageously be combined with an excipient for form a composition such that an ordinarily skilled artisan at time of filing or invention would have been motivated to do the same regarding any oil suggested by the reference claims.
Claims 67-96 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,925,850 in view of Apt et al. (U.S. 2010/0239533 A1).
Claims 67-96 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 9,611,488 in view of Apt et al. (U.S. 2010/0239533 A1).
Claims 67-96 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 9,222,112 in view of Apt et al. (U.S. 2010/0239533 A1).
Claims 67-96 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 9,649,287 in view of Apt et al. (U.S. 2010/0239533 A1).
Claims 67-96 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 9,968,578 in view of Apt et al. (U.S. 2010/0239533 A1).
The ‘850, ‘488, ‘112, ‘287, and ‘578 patents share the same specification.
The reference claims include:
‘578 patent:
1. A microbial oil comprising omega-3 polyunsaturated fatty acids comprising DHA and EPA in an amount of about >90%, by weight, of the total amount of omega-3 polyunsaturated fatty acids, and DPA n-3 is in an amount of from about 0% to about 10%, by weight, of the total amount of omega-3 polyunsaturated fatty acids, wherein the amount of EPA, by weight, is from about 28% to about 36% of the total amount of DHA and EPA, and the amount of DHA, by weight, is from about 54% to about 62% of the total amount of DHA and EPA, wherein said microbial oil further comprising an effective amount of at least on added antioxidant.
2. A microbial oil comprises omega-3 polyunsaturated fatty acids comprising DHA and EPA in an amount of about >90%, by weight, of the total amount of omega-3 polyunsaturated fatty acids, and DPA n-3 is in an amount of from about 0% to about 2%, by weight, of the total amount of omega-3 polyunsaturated fatty acids, wherein the amount of EPA, by weight, is from about 10% to about 25% of the total amount of DHA and EPA, and the amount of DHA, by weight, is from about 75% to about 90% of the total amount of DHA and EPA, wherein said microbial oil further comprising an effective amount of at least on added antioxidant.
6. The oil of claim 1 or claim 2, wherein the microbial oil comprises from about 120 mg to about 220 mg EPA per one gram of oil and from about 240 mg to about 450 mg DHA per one gram of oil.
7. The oil of claim 1, wherein the microbial oil comprises from about 150 mg to about 300 mg EPA per one gram of oil; from about 200 mg to about 400 mg DHA per one gram of oil; and from about 0 to about 55 mg DPA n-3 per one gram of oil.
8. The oil of claim 2, wherein the microbial oil comprises from about 50 mg to about 150 mg EPA per one gram of oil; from about 410 mg to about 540 mg DHA per one gram of oil; and from about 0 to about 12 mg DPA n-3 per one gram of oil.
9. The oil of claim 1 or claim 2, wherein the microbial oil comprises a ratio of EPA:DHA of 1:1 to 1:30 or 1:1 to 1:3 by weight of total omega-3 polyunsaturated fatty acids.
‘287 patent:
1. A microbial oil comprising omega-3 polyunsaturated fatty acids comprising DHA and EPA in an amount of about >90%, by weight, of the total amount of omega-3 polyunsaturated fatty acids, and DPA n-3 is in an amount of from about 0% to about 10%, by weight, of the total amount of omega-3 polyunsaturated fatty acids, wherein the amount of EPA, by weight, is from about 28% to about 36% of the total amount of DHA and EPA, and the amount of DHA, by weight, is from about 54% to about 62% of the total amount of DHA and EPA.
2. A microbial oil comprises omega-3 polyunsaturated fatty acids comprising DHA and EPA in an amount of about >90%, by weight, of the total amount of omega-3 polyunsaturated fatty acids, and DPA n-3 is in an amount of from about 0% to about 2%, by weight, of the total amount of omega-3 polyunsaturated fatty acids, wherein the amount of EPA, by weight, is from about 10% to about 25% of the total amount of DHA and EPA, and the amount of DHA, by weight, is from about 75% to about 90% of the total amount of DHA and EPA.
6. The oil of claim 1 or claim 2, wherein the microbial oil comprises from about 120 mg to about 220 mg EPA per one gram of oil and from about 240 mg to about 450 mg DHA per one gram of oil.
7. The oil of claim 1, wherein the microbial oil comprises from about 150 mg to about 300 mg EPA per one gram of oil; from about 200 mg to about 400 mg DHA per one gram of oil; and from about 0 to about 55 mg DPA n-3 per one gram of oil.
8. The oil of claim 2, wherein the microbial oil comprises from about 50 mg to about 150 mg EPA per one gram of oil; from about 410 mg to about 540 mg DHA per one gram of oil; and from about 0 to about 12 mg DPA n-3 per one gram of oil.
9. The oil of claim 1 or claim 2, wherein the microbial oil comprises a ratio of EPA:DHA of 1:1 to 1:30 or 1:1 to 1:3 by weight of total omega-3 polyunsaturated fatty acids.
‘578 patent:
1. A microbial oil comprising omega-3 polyunsaturated fatty acids comprising DHA and EPA in an amount of about >90%, by weight, of the total amount of omega-3 polyunsaturated fatty acids, and DPA n-3 is in an amount of from about 0% to about 10%, by weight, of the total amount of omega-3 polyunsaturated fatty acids, wherein the amount of EPA, by weight, is from about 28% to about 36% of the total amount of DHA and EPA, and the amount of DHA, by weight, is from about 54% to about 62% of the total amount of DHA and EPA, wherein said microbial oil further comprising an effective amount of at least on added antioxidant.
2. A microbial oil comprises omega-3 polyunsaturated fatty acids comprising DHA and EPA in an amount of about >90%, by weight, of the total amount of omega-3 polyunsaturated fatty acids, and DPA n-3 is in an amount of from about 0% to about 2%, by weight, of the total amount of omega-3 polyunsaturated fatty acids, wherein the amount of EPA, by weight, is from about 10% to about 25% of the total amount of DHA and EPA, and the amount of DHA, by weight, is from about 75% to about 90% of the total amount of DHA and EPA, wherein said microbial oil further comprising an effective amount of at least on added antioxidant.
‘850 patent:
5. A microbial oil comprising omega-3 polyunsaturated fatty acids comprising docosahexaenoic acid and eicosapentaenoic acid in an amount of about >90%, by weight, of the total amount of omega-3 polyunsaturated fatty acids, wherein the amount of eicosapentaenoic acid, by weight, is from about 19% to about 55% of the total amount of docosahexaenoic acid and eicosapentaenoic acid, and the amount of docosahexaenoic acid, by weight, is from about 35% to about 71% of the total amount of docosahexaenoic acid and eicosapentaenoic acid, wherein the total amount of omega-3 polyunsaturated fatty acids is at least about 400 mg per one gram of oil, and wherein said microbial oil further comprising an effective amount of at least one added antioxidant.
6. The oil of any one of claims 1-5, wherein said oil is produced by Schizochytrium sp.
7. The oil of any one of claims 1-5, wherein said oil comprises less that about 5% by weight of each of arachidonic acid, docosapentaenoic acid n-6, oleic acid, linoleic acid, linolenic acid, eicosenoic acid, erucic acid and stearidonic acid.
8. A microbial oil comprising a triacylglycerol fraction of at least 10% by weight, wherein at least about 12% by weight of the fatty acids in the triacylglycerol fraction is eicosapentaenoic acid, wherein at least 25% by weight of the fatty acids in the triacylglycerol fraction is docosahexaenoic acid, wherein said oil has a peroxide value of 5 or less, and wherein said microbial oil further comprising an effective amount of at least one added antioxidant.
9. The oil of any one of claims 1-5, wherein said oil comprises a ratio of EPA:DHA selected from 1:1 to 1:1.5, 1:1 to 1:2, 1:1.5 to 1:2, 1:1 to 1:2.5, 1:2 to 1:2.5, and 1:4 to 1:7 by weight of total omega-3 polyunsaturated fatty acids.
10. A microbial oil comprising 120 mg to 220 mg eicosapentaenoic acid per one gram of oil and from 240 mg to 450 mg docosahexaenoic acid per one gram of oil, and wherein said microbial oil further comprising an effective amount of at least one added antioxidant.
11. The oil of claim 9, wherein said oil is produced by Schizochytrium sp.
‘488 patent:
7. A microbial oil comprising a triacylglycerol fraction of at least 10% by weight, wherein at least about 12% by weight of the fatty acids in the triacylglycerol fraction is eicosapentaenoic acid, wherein at least 25% by weight of the fatty acids in the triacylglycerol fraction is docosahexaenoic acid, wherein less than 5% by weight of the fatty acids in the triacylglycerol fraction is arachidonic acid, and wherein the oil comprises from 120 mg to 220 mg eicosapentaenoic acid per one gram of oil and from 240 mg to 450 mg docosahexaenoic acid per one gram of oil.
8. The oil of any one of claims 1-4, and 7, wherein said oil comprises a ratio of EPA:DHA selected from 1:1 to 1:1.5, 1:1 to 1:2, 1:1.5 to 1:2, 1:1 to 1:2.5, 1:2 to 1:2.5, and 1:4 to 1:7 by weight of total omega-3 polyunsaturated fatty acids.
9. A microbial oil comprising 120 mg to 220 mg eicosapentaenoic acid per one gram of oil and from 240 mg to 450 mg docosahexaenoic acid per one gram of oil.
10. The oil of claim 9, wherein said oil is produced by Schizochytrium sp.
‘112 patent:
1. A microbial oil comprising omega-3 polyunsaturated fatty acids comprising docosahexaenoic acid and eicosapentaenoic acid in an amount of about ≧90%, by weight, of the total amount of omega-3 polyunsaturated fatty acids, wherein the amount of eicosapentaenoic acid, by weight, is from about 19% to about 55% of the total amount of docosahexaenoic acid and eicosapentaenoic acid, and the amount of docosahexaenoic acid, by weight, is from about 35% to about 71% of the total amount of docosahexaenoic acid and eicosapentaenoic acid, wherein the total amount of omega-3 polyunsaturated fatty acids is at least about 400 mg per one gram of oil.
2. The oil of claim 1, wherein the amount of eicosapentaenoic acid, by weight, is from about 19% to about 43% of the total amount of docosahexaenoic acid and eicosapentaenoic acid, and the amount of docosahexaenoic acid, by weight, is from about 35% to about 47% of the total amount of docosahexaenoic acid and eicosapentaenoic acid.
3. The oil of claim 1, wherein the amount of eicosapentaenoic acid, by weight, is from about 27% to about 54% of the total amount of docosahexaenoic acid and eicosapentaenoic acid, and the amount of docosahexaenoic acid, by weight, is from about 36% to about 63% of the total amount of docosahexaenoic acid and eicosapentaenoic acid.
4. The oil of claim 1, wherein the amount of eicosapentaenoic acid, by weight, is from about 26% to about 38% of the total amount of docosahexaenoic acid and eicosapentaenoic acid, and the amount of docosahexaenoic acid, by weight, is from about 52% to about 64% of the total amount of docosahexaenoic acid and eicosapentaenoic acid.
5. The oil of claim 1, wherein the amount of eicosapentaenoic acid, by weight, is from about 28% to about 36% of the total amount of docosahexaenoic acid and eicosapentaenoic acid, and the amount of docosahexaenoic acid, by weight, is from about 54% to about 62% of the total amount of docosahexaenoic acid and eicosapentaenoic acid.
6. The oil of claim 1, wherein said oil is produced by Schizochytrium sp.
7. The oil of claim 1, wherein said oil comprises less that about 5% by weight of each of arachidonic acid, docosapentaenoic acid n-6, oleic acid, linoleic acid, linolenic acid, eicosenoic acid, erucic acid and stearidonic acid.
8. The oil of claim 1, wherein said oil comprises a triacylglycerol fraction of at least about 10% by weight, wherein at least about 12% by weight of the fatty acids in the triacylglycerol fraction is eicosapentaenoic acid, wherein at least about 25% by weight of the fatty acids in the triacylglycerol fraction is docosahexaenoic acid and wherein less that about 5% by weight of the fatty acids in the triacylglycerol fraction is arachidonic acid.
9. The oil of claim 1, wherein the total amount of docosahexaenoic acid and eicosapentaenoic acid is about 400 mg per one gram of oil.
“In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.” “Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.” MPEP 2144.05(I).
The claims recite a microbial oil (contained within a biomass) or a microbial oil that has a triglyceride (TAG) fraction reciting amounts of DHA and EPA that overlap or are otherwise close to the ranges recited in the rejected claims as to establish a prima facie case of obviousness. It is noted that the claims recite concentration of DHA and EPA for the microbial oil and not specifically the TAG fraction. However, it would appear that there is a close relationship to the fatty acid content of the TAG fraction and the overall microbial oil such that an ordinarily skilled artisan at time of invention or filing would understand the recited concentrations of DHA and EPA to be applicable to a TAG fraction as well. Further, specific concentrations of DHA and EPA within these ranges satisfy the recitation of EPA is from 36-65% of total amount of EPA and DHA as to be encompassed by overlapping or close ranges being prima facie obvious.
Regarding recitation of a triacylglycerol (TAG) fraction being 65-98% by weight (and subranges thereof) a recited in the rejected claims, the reference claims positively recite a TAG fraction that is at least 10% by weight. Apt (para. [0023]), as discussed above, teaches microbial oils wherein “The present invention is also directed to a microbial oil comprising a triglyceride fraction of at least about 70% by weight, and for example, provides a specific example of a microbial oil with 82.7% TAG fraction by weight. Apt, para. [0120]. Since microbial oils having a TAG fraction falling with the recited range of 65-98% by weight (and subranges thereof) are established in the prior art, at the time of filing or invention it is not considered to be inventive to form embodiments of the reference claims having similar TAG content.
The reference claims do not recite 0.1% to 5% by weight of ARA and other recited ranges of ARA. The teachings of Apt discussed above are incorporated herein by reference. Apt, Table 25, and related discussion in Apt teach that it is common for microbial oils from Thraustochytrid organisms including Thraustochytrium) to contain a minor amount of ARA falling within a range of 0.1-5%. Similarly, Apt, para. [0057], teaches that it is known and common for such microbial oils to contain a sterol fraction including 0.5% by weight such that it would have been obvious at time of filing or invention for the microbial oil of the reference claims to be consistent with the same. Further, nothing in the reference claims indicates any requirement or presence of omega-3 fatty acids other than DHA and EPA to be present as to meet the requirement that over 90% of omega-3 fatty acids present in any microbial oil or TAG fraction be DHA or EPA. Less than 5% by weight as recited in claims 73 and 84 includes zero as less than 5%. As far as the specific fatty acids recited in claims 73 and 84 are not recited in the reference claims, it would have been obvious at time of filing or invention for the same to not be present or present in low amounts less than 5% in any embodiment microbial oil or TAG fraction of the reference claims.
Regarding claim 96, a “composition of the invention can include one or more excipients.” Apt, para. [0064]. As such, Apt directly teaches that any microbial oil can advantageously be combined with an excipient for form a composition such that an ordinarily skilled artisan at time of filing or invention would have been motivated to do the same regarding any oil suggested by the reference claims.
Regarding claim 96, a “composition of the invention can include one or more excipients.” Apt, para. [0064]. As such, Apt directly teaches that any microbial oil can advantageously be combined with an excipient for form a composition such that an ordinarily skilled artisan at time of filing or invention would have been motivated to do the same regarding any oil suggested by the reference claims.
Claims 67-96 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 9,101,151 in view of Apt et al. (U.S. 2010/0239533 A1), Volkman (Sterols in microorganisms, Appl Microbial Biotechnol 60, 2003, 495-506), Pirronen et al. (Plant sterols: biosynthesis, biological function and their importance to human nutrition, J. Sci. Food, Agricul. 80, 2000, 939-66) Kralovec et al (WO 2009/040676 A2) and Singh et al. (Docosahexaenoic acid (DHA) production by Thraustochytrium sp. ATCC 20892, World J. Microbiol. Biotechnol. 17, 1996, 76-81).
Claims 67-96 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 9,408,404 in view of Apt et al. (U.S. 2010/0239533 A1), Volkman (Sterols in microorganisms, Appl Microbial Biotechnol 60, 2003, 495-506), Pirronen et al. (Plant sterols: biosynthesis, biological function and their importance to human nutrition, J. Sci. Food, Agricul. 80, 2000, 939-66), Kralovec et al. (WO 2009/040676 A2) and Singh et al. (Docosahexaenoic acid (DHA) production by Thraustochytrium sp. ATCC 20892, World J. Microbiol. Biotechnol. 17, 1996, 76-81).
The ‘151 and ‘404 patents share the same specification or a priority claim.
The reference claims include:
‘151 patent:
1. A refined, bleached, or deodorized microbial or plant lipid comprising polyunsaturated fatty acid, wherein said lipid has an anisidine value of 1.5 or less, wherein said lipid has been liberated from biomass enzymatically and through addition of a surfactant, and wherein said polyunsaturated fatty acid present in said lipid comprises at least 20 weight percent docosahexaenoic acid, at least 5 weight percent docosapentaenoic acid, or at least 20 weight percent arachidonic acid.
2. The lipid of claim 1, wherein said polyunsaturated fatty acid is docosahexaenoic acid.
3. The lipid of claim 1, wherein said polyunsaturated fatty acid is docosapentaenoic acid.
5. The lipid of claim 1, wherein said polyunsaturated fatty acid comprises at least 30 weight percent docosahexaenoic acid.
6. The lipid of claim 1, wherein said polyunsaturated fatty acid comprises at least 35 weight percent docosahexaenoic acid.
7. The lipid of claim 1, wherein said polyunsaturated fatty acid comprises at least 10 weight percent docosapentaenoic acid.
8. The lipid of claim 1, wherein said polyunsaturated fatty acid comprises at least 15 weight percent docosapentaenoic acid.
9. The lipid of claim 1, wherein said polyunsaturated fatty acid comprises at least 20 weight percent docosapentaenoic acid.
17. The lipid of claim 1, wherein said lipid is obtained from microorganisms selected from the group consisting of the genus Thraustochytrium, genus Schizochytrium or mixtures thereof.
20. The lipid of claim 1, wherein said lipid comprises a triacylglyceride.
From the ‘404 patent:
1. A method for obtaining a polyunsaturated fatty acid-containing lipid from a biomass, comprising:
a) contacting an enzyme and a surfactant with a biomass at a temperature of about 10 degree Celsius to about 80 degree Celsius, and at a pH level of about pH 5 to about pH 9, said enzyme degrading a portion of the biomass impeding recovery of the lipid, and the portion of the biomass is selected from the group consisting of proteins, polysaccharides, cell wall, outer cell membrane, peptidoglycan layer, lipid bilayer, cellulose, chitin, hemicellulose, lignin, and lignin-related compounds,
b) recovering said lipid having an anisidine value of 0.8 comprising at least 20 weight percent docosahexaenoic acid, at least 5 weight percent docosapentaenoic acid, and/or at least 20 weight percent arachidonic acid; and
c) treating the recovered lipid by refining, bleaching, or deodorizing.
7. The method of claim 1, wherein the biomass comprises a microorganism selected from the group consisting of the genus Thraustochytrium, genus Schizochytrium, genus Althornia, genus Aplanochytrium, genus Japonochytrium, genus Labyrinthula, and genus Labyrithuloides.
31. The method of claim 1, wherein said polyunsaturated fatty acid comprises at least 30 weight percent docosahexaenoic acid.
32. The method of claim 1, wherein said polyunsaturated fatty acid comprises at least 10 weight percent docosapentaenoic acid.
33. The method of claim 1, wherein said polyunsaturated fatty acid comprises at least 15 weight percent docosapentaenoic acid.
34. The method of claim 1, wherein said polyunsaturated fatty acid comprises at least 20 weight percent docosapentaenoic acid.
40. The method of claim 1, wherein said lipid comprises a triacylglycerol.
“In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.” “Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.” MPEP 2144.05(I).
The claims recite a microbial oil that has a triglyceride (TAG) fraction reciting amounts of DHA and that overlap or are otherwise close to the ranges recited in the rejected claims as to establish a prima facie case of obviousness for concentration of DHA recited in the claims.
The patented claims are silent regarding presence of EPA and the patented claims do not require ARA above 20%. The rejections under 35 U.S.C. 103 over Apt et al. (U.S. 2010/0239533 A1), Volkman (Sterols in microorganisms, Appl Microbial Biotechnol 60, 2003, 495-506), Pirronen et al. (Plant sterols: biosynthesis, biological function and their importance to human nutrition, J. Sci. Food, Agricul. 80, 2000, 939-66), Kralovec et al. (WO 2009/040676 A2) and Singh et al. (Docosahexaenoic acid (DHA) production by Thraustochytrium sp. ATCC 20892, World J. Microbiol. Biotechnol. 17, 1996, 76-81) stated above are incorporated herein by reference. The patented claims recite a microbial oil with broad ranges of DHA and open to the presence of EPA, and ARA and sterol that are “refined.” Upon producing an oil meeting the features of claims 67-96 as set forth in the rejections under 35 U.S.C. 103 above, performing of any act of refinement on such an oil as suggested by the cited prior art is an embodiment of the patented claims, wherein the prior art directly teaches and suggest to an ordinarily skilled artisan at time of filing or invention that such refinement should be done: “The invention is further directed to a microbial oil comprising a fatty acid profile of the invention. A microbial oil of the invention can be any oil derived from a microorganism, including, for example: a crude oil extracted from the biomass of the microorganism without further processing; a refined oil that is obtained by treating a crude microbial oil with further processing steps such as refining, bleaching, and/or deodorizing; a diluted microbial oil obtained by diluting a crude or refined microbial oil; or an enriched oil that is obtained, for example, by treating a crude or refined microbial oil with further methods of purification to increase the concentration of a fatty acid (such as DHA) in the oil.” Apt, para. [0056].
The patented claims are narrower than the rejected claims as far as the patented claims recite limitations related to anisidine value that are measures of aldehyde and ketone oxidation products that can be present in an oil. However, preparation of an oil as suggested by Apt et al. (U.S. 2010/0239533 A1), Kralovec et al. (WO 2009/040676 A2), Volkman (Sterols in microorganisms, Appl Microbial Biotechnol 60, 2003, 495-506), Pirronen et al. (Plant sterols: biosynthesis, biological function and their importance to human nutrition, J. Sci. Food, Agricul. 80, 2000, 939-66) and Singh et al. (Docosahexaenoic acid (DHA) production by Thraustochytrium sp. ATCC 20892, World J. Microbiol. Biotechnol. 17, 1996, 76-81) further “refined” in accordance with the anisidine value limitations taught by the patented claims yields embodiments that meet the features of the rejected claims that are silent regarding anisidine values.
Apt, para. [0057], teaches that it is known and common for such microbial oils to contain a sterol fraction including 0.5% by weight such that it would have been obvious at time of filing or invention for the microbial oil of the reference claims to be consistent with the same. Further, nothing in the reference claims indicates any requirement or presence of omega-3 fatty acids other than DHA and EPA to be present. Less than 5% by weight as recited in claims 73 and 84 includes zero as less than 5%. As far as the specific fatty acids recited in claims 73 and 84 are not recited in the reference claims, it would have been obvious at time of filing or invention for the same to not be present or present in low amounts less than 5% in any embodiment microbial oil or TAG fraction of the reference claims.
For these reasons, an ordinarily skilled artisan at time of filing or invention would have been motivated to produce embodiments of the patented claims that reach the features of the rejected claims.
Regarding claim 96, a “composition of the invention can include one or more excipients.” Apt, para. [0064]. As such, Apt directly teaches that any microbial oil can advantageously be combined with an excipient for form a composition such that an ordinarily skilled artisan at time of filing or invention would have been motivated to do the same regarding any oil/lipid suggested by the reference claims.
Claims 67-96 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,666,062 in view of Apt et al. (U.S. 2010/0239533 A1).
Claims of ‘062 patent recite:
1. An oil comprising:
at least 25% by weight omega-3 polyunsaturated fatty acids (LC-PUFA), wherein
the oil has a residual moisture content which comprises less than 5% by weight of free fatty acid in the residual moisture of the oil, and wherein
the oil comprises at least 25% by weight docosahexaenoic acid (DHA), and at least 10% by weight eicosapentaenoic acid (EPA), and wherein
the omega-3 polyunsaturated fatty acids are present in the oil in a total amount of at least 500 mg per one gram of oil.
3. The oil according to claim 1, wherein the EPA is present in the oil in an amount from 100 mg to 250 mg EPA per one gram of oil, and the DHA is present in the oil in an amount from 250 mg to 400 mg DHA per one gram of oil.
4. The oil according to claim 3, wherein the oil comprises a weight ratio of the EPA:DHA of 1:1 to 1:30 based on total weight of the omega-3 polyunsaturated fatty acids.
11. The microbial oil according to claim 6, comprising at least 10% by weight of a triacylglycerol fraction, wherein
at least 12% by weight of the fatty acids in the triacylglycerol fraction is eicosapentaenoic acid, and wherein
at least 25% by weight of the fatty acids in the triacylglycerol fraction is docosahexaenoic acid, and wherein
less than 5% by weight of the fatty acids in the triacylglycerol fraction is arachidonic acid.
“In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.” “Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.” MPEP 2144.05(I).
The claims recite a microbial oil (contained within a biomass) or a microbial oil that has a triglyceride (TAG) fraction reciting amounts of DHA and EPA that overlap or are otherwise close to the ranges recited in the rejected claims as to establish a prima facie case of obviousness. It is noted that the claims recite concentration of DHA and EPA for TAG fraction and not for an overall oil. However, it would appear that there is a close relationship to the fatty acid content of the TAG fraction and the overall microbial oil such that an ordinarily skilled artisan at time of invention or filing would understand the recited concentrations of DHA and EPA to be applicable to an overall oil as well. Further, specific concentrations of DHA and EPA within these ranges satisfy the recitation of EPA is from 36-65% of total amount of EPA and DHA as to be encompassed by overlapping or close ranges being prima facie obvious.
Regarding recitation of a triacylglycerol (TAG) fraction being 65-98% by weight (and subranges thereof) a recited in the rejected claims, the reference claims positively recite a TAG fraction that is at least 10% by weight. Apt (para. [0023]), as discussed above, teaches microbial oils wherein “The present invention is also directed to a microbial oil comprising a triglyceride fraction of at least about 70% by weight, and for example, provides a specific example of a microbial oil with 82.7% TAG fraction by weight. Apt, para. [0120]. Since microbial oils having a TAG fraction falling with the recited range of 65-98% by weight (and subranges thereof) are established in the prior art, at the time of filing or invention it is not considered to be inventive to form embodiments of the reference claims having similar TAG content.
The reference claims do not recite 0.1% to 5% by weight of ARA and other recited ranges of ARA. The teachings of Apt discussed above are incorporated herein by reference. Apt, Table 25, and related discussion in Apt teach that it is common for microbial oils from Thraustochytrid organisms including Thraustochytrium) to contain a minor amount of ARA falling within a range of 0.1-5%. Similarly, Apt, para. [0057], teaches that it is known and common for such microbial oils to contain a sterol fraction including 0.5% by weight such that it would have been obvious at time of filing or invention for the microbial oil of the reference claims to be consistent with the same. Further, nothing in the reference claims indicates any requirement or presence of omega-3 fatty acids other than DHA and EPA to be present as to meet the requirement that over 90% of omega-3 fatty acids present in any microbial oil or TAG fraction be DHA or EPA. Less than 5% by weight as recited in claims 73 and 84 includes zero as less than 5%. As far as the specific fatty acids recited in claims 73 and 84 are not recited in the reference claims, it would have been obvious at time of filing or invention for the same to not be present or present in low amounts less than 5% in any embodiment microbial oil or TAG fraction of the reference claims.
Regarding claim 96, a “composition of the invention can include one or more excipients.” Apt, para. [0064]. As such, Apt directly teaches that any microbial oil can advantageously be combined with an excipient for form a composition such that an ordinarily skilled artisan at time of filing or invention would have been motivated to do the same regarding any oil suggested by the reference claims.
Response to arguments
Applicant argues:
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“The one or more fractions isolated from the thraustochytrid includes the total fatty acid fraction, the sterol esters fraction, the triglyceride fraction, the free fatty acid fraction, the sterol fraction, the diglyceride fraction, the polar fraction (including the phospholipid fraction), and combinations thereof.” Apt, para. [0045]. “The one or more fractions isolated from the thraustochytrid includes the total fatty acid fraction, the sterol esters fraction, the triglyceride fraction, the free fatty acid fraction, the sterol fraction, the diglyceride fraction, the polar fraction (including the phospholipid fraction), and combinations thereof. . . . n some embodiments, the microbial oil comprises a triglyceride fraction of from about 65% to about 95%, about 75% to about 95%, or about 80% to about 95% by weight, or about 97% by weight, or about 98% by weight” Apt, para. [0057].
As such, Apt suggests making “combinations” of isolated fractions can be in combination and that any embodiment microbial oil would not be more than 5% while being up to 98% the TAG fraction. As such, Apt does not describe that the sterol fraction is “discarded” but has a benefit to be included in a microbial oil. This is further supported by Volkman teaching that sterol esters have nutritional benefits. Kralovec does not serve as a source of motivation for addition of a sterol ester, wherein such motivation is from Apt and Volkman.
Applicant argues:
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All data presented in the specification describes the fatty acid profile composition of a biomass of cells. There is no apparent description in the specification of the EPA/DHA/ARA composition of an isolated microbial oil being 65%-98% by weight of a TAG fraction as recited in at least claim 67. For example, para. [0021], describes “All cultures were harvested after 7 days, and FAME analysis was performed on the final freeze-dried biomass samples,” with apparent results presented in the table in para. [00214]. Such freeze dried biomass is not an embodiment microbial oil being 65%-98% by weight of a TAG fraction as recited in at least claim 67 regardless of the EPA/DHA/ARA content thereof. The extent to which the fatty acid composition as found in a whole cell biomass will reflect the composition of a TAG fraction or microbial oil produced therefrom is a matter of speculation. For example, Apt., Table 25, shows differences between fatty acid composition of a biomass and oil purified therefrom. All of the description of the working examples appears to be for a whole biomass rather than a microbial oil being 65%-98% by weight of a TAG fraction. If such a working example of microbial oil with 65%-98% by weight of a TAG fraction is present in the voluminous amount of data presented, the same can be highlighted with specificity.
Applicant argues:
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Kralovec discloses ability to significantly increase PUFA (EPA and DHA) content of a microbial oil primarily by replacing C16 fatty acid with EPA or DHA. Referring only to Table 9.1 (describing the lipid in Table 9.2), C16:0 saturated fatty acid is reduced from 35.4% to 17.3% while EPA (C20:5) is increased from 0.6% to 12.4% (a 20-fold increase) and DHA (C22:6) is increased from 4.6 to 7.3%.
Table 9.1 of Kralovec starts from an oil that is particularly low in EPA and DHA (particularly low in EPA); however, the evidence of record supports that if the starting point is an oil with higher EPA and DHA as reviewed in the body of the rejection than a microbial oil having the limitations of the claims can be reached. Again, the teachings of Kralovec are not limited to its working examples. Similarly, the specification contains no working examples of a microbial oil having 65%-98% by weight of a TAG fraction and meeting the other limitations of the claims.
Applicant argues:
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The claims do not recite a method and the microbial oil recited in the claims is not required to be produced by any particular method.
Applicant argues:
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The evidence of record supports the following statements of fact:
Embodiments of the claims can be made by refining or mixing individual TAG molecules and sterol esters. The microbial oils are not only achieved via artificial culture conditions. See specification, para. [0156] (by treating microbial oil with further methods of purification to increase the concentration of a fatty acid (such as DHA) in the oil).
Embodiments of the claims can be made by blending or mixing two or more naturally-occurring microbial oils to make an oil meeting the limitations of the claims, or by adding a purified TAG, sterol, etc., to a microbial oil.
Individual TAG molecules and sterol esters that can be mixed to produce embodiment compositions of the claims are all individually naturally-occurring compounds and products of nature each having a naturally-occurring counterpart.
Embodiments of the claims are not required to be produced directly by culturing a microorganism; no rejected claims are directed towards a method.
“It is important to keep in mind that product of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart.” MPEP 2106.04(b)(II).
That is, all non-naturally occurring products require “human intervention and control.” However, just because a product is made or can only be made by man is not sufficient for patent eligibility under the judicial exception. The inoculants of Funk Bros. also required “human intervention and control.” It is noted that the MPEP directs that the markedly different characteristic analysis is specifically required when the nature-based product limitation is not naturally occurring: “Examiners should keep in mind that if the nature-based product limitation is naturally occurring, there is no need to perform the markedly different characteristics analysis because the limitation is by definition directed to a naturally occurring product and thus falls under the product of nature exception. However, if the nature-based product limitation is not naturally occurring, for example due to some human intervention, then the markedly different characteristics analysis must be performed to determine whether the claimed product limitation is a product of nature exception.” MPEP 2106.04(c)(I).
The claims present a scenario wherein the product of nature exception applies to a non-naturally occurring product that lacks markedly different characteristics from any naturally occurring counterpart. The fact that the claims recite a mixture that does not occur in nature does not amount to a markedly different chrematistic in itself (i.e. has a different fatty acid composition), since if the same were true than no non-naturally composition will fall within the product of nature exception as set forth in MPEP 2106.04(b)(II). For example, “Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130, 76 USPQ 280, 281 (1948) (claims to [non-natural] bacterial mixtures held ineligible as ‘manifestations of laws of nature’ and ‘phenomena of nature’)." MPEP 2106.04(b)(II). Likewise, claims to nucleic acid primers, while not existing in nature, have been found to lack markedly different characteristics from their naturally-occurring counterpart: Similarly, assume that applicant claims a single-stranded piece of DNA (a primer) having a nucleotide sequence derived from the sense strand of naturally occurring nucleic acid C. Although nucleic acid C occurs in nature as a double-stranded molecule having a sense and an antisense strand, the closest natural counterpart for the claimed nucleic acid is the sense strand of C only. See, e.g., University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 760, 113 USPQ2d 1241, 1241 (Fed. Cir. 2014) (comparing single-stranded nucleic acid to the same strand found in nature, even though "single-stranded DNA cannot be found in the human body"). MPEP 2106.04(c)(I)(A).
Each discrete TAG and sterol ester compound forming a microbial oil is understood as being naturally-occurring and chemically identical to its naturally occurring counterpart. The proportions to which such naturally-occurring TAG and ester compounds are artificially mixed in combination in itself does not amount to a markedly different characteristic. Further, the only property identified so far is the nutritional quality of the microbial oil. However, the nutritional property of each individual chemical component forming the mixture would not appear to be changed by combination in a mixture.
Regarding applicant arguments distinguishing from “Claim 1 of Example 3” (amazonic acid), the recitation of 65-98% by weight is a recitation of a degree of purification. The same is not a recitation of a change in chemical structure wherein all of the individual chemical components of a microbial oil are chemically unchanged from their natural counterpart. That is, a TAG compound present that may be glycerol esterified to three DHA, or three EPA, or two DHA and a C16 fatty acid, individual sterol compounds, etc., all remain chemically the same with no chemical reaction occurring and no change is covalent bonding. That is, embodiments of the claims are mixtures of specific chemical compounds characterized by a specific chemical formula and molecular weight, which are unchanged from naturally occurring counterparts. For example, triacylglycerol fully esterified with docosahexaenoic acid is CAS 124596-98-1 with molecular formula C69H98O6 and can be one of the many components of an embodiment of the claims and is naturally-occurring (Apt et al. U.S. 2010/0239533 A1, Table 9). This is in contrast to 5-methyl amazonic acid and deoxyamazonic acid that have different chemical structure in terms of chemical formula and molecular weight with respect to amazonic acid, embodiments of the claims do not change the chemical identity of any compound. No components of the recited microbial oil are required to have a change in chemical formula or molecular weight from its naturally-occurring counterpart.
As discussed in the body of the rejection, embodiments of the claims can be made by mixing and blending oils and their components with no change in chemical structure occurring. Just as purified naturally-occurring compounds can fall within the judicial exception, mixtures of naturally-occurring compounds can fall within the judicial exception in the absence of a markedly different characteristic.
Conclusion
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/TODD M EPSTEIN/Primary Examiner, Art Unit 1652
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