DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a national stage entry of PCT/IB2020/053553 filed on 04/15/2020. Acknowledgment is made of applicant's claim for foreign priority based on an application filed in INDIA on 04/16/2019. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 August 14, 2025 has been entered.
Response to Amendment
By Applicant’s amendment filed on August 14, 2025 claim 1 has been amended. Claims 12-14 and 16-17 were previously canceled. Claims 1-11, 15 and 18-21 are currently pending and presented for examination.
Response to Arguments
Applicant's arguments filed August 14, 2025 have been fully considered but they are not persuasive.
Applicant argues that Yeum does not disclose the claimed feature that the natural lutein is derived from marigold flowers, rather Yeum discloses that the lutein can be obtained from green leafy vegetables. Applicant argues that there is no disclosure in Yeum of the claimed feature that the dietary supplement composition slows the rate of telomere shortening in vitro by at least 20%. Applicant argues that Yeum only contemplates protection against lymphocyte DNA damage and free-radical associated disorders in a subject and does not contemplate telomere shortening. Applicant argues that there is not even a single mention of the word "telomere" within the disclosure of Yeum. Applicant further argues that the instant invention has a defined composition of 10 mg lutein + 2 mg zeaxanthin + at least one biological compound selected from carotenoid, an antioxidant, a vitamin, mineral salts and/or trace elements, acceptable additives or a second natural extract, whereas Yeum has lutein + 1mg to 20 mg beta-carotene or about 0.1 to 20 mg lycopene.
These arguments are found not persuasive because Applicant has not provided any evidence that lutein derived from marigold flowers is the only source of lutein that will produce the effect on telomere shortening. Thus in the absence of such evidence, the effect on telomere shortening is an inherent effect of the lutein component itself which is the only active component required in claim 1 of the instant application since as stated by Applicant, the tocopherol component in the amount as claimed is to stabilize the lutein. A compound and its properties are inseparable. In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963). Thus it is maintained that the method of Yeum which comprises administering lutein for reducing DNA damage will necessarily have the same effect on telomeres as claimed.
Furthermore, there is no requirement in the instant claims to administer a defined composition of 10 mg lutein + 2 mg zeaxanthin + at least one biological compound selected from carotenoid, an antioxidant, a vitamin, mineral salts and/or trace elements, acceptable additives or a second natural extract. The only claim of the instant application that requires a specific amount of lutein is claim 19 which requires an effective dose of lutein as 6 mg to 10 mg per day. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a defined composition of 10 mg lutein + 2 mg zeaxanthin + at least one biological compound selected from carotenoid, an antioxidant, a vitamin, mineral salts and/or trace elements, acceptable additives or a second natural extract) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Yeum teaches a pharmaceutical composition for use in decreasing DNA damage and/or for use in protecting against a free radical associated disorder comprising an effective daily dose of about 0.1 to 20 mg lutein [0010]. Yeum further teaches a particularly preferred dosage of lutein for decreasing DNA damage is 2 to 10 mg per day [0030]. Thus the amount taught in Yeum for lutein overlaps with the amount as required in the instant claims which has the effect as claimed on telomeres. Thus, it is maintained that administering the same amount of lutein for the same purpose of decreasing DNA damage and protecting against a free radical (oxidative) damage will necessarily have the same effects as claimed which is slowing the rate of telomere shortening in vitro by at least 20%.
In addition, even though Yeum discloses that the lutein can be obtained from green leafy vegetables, Yeum does not specifically teach how to obtain the lutein and does not teach or suggest that other sources would not be useful in the claimed method. It would have been obvious to a person of ordinary skill in the art to prepare the components for use in the method of Yeum by any suitable method known in the art. Furthermore, a person of ordinary skill in the art would have been motivated to use any source for lutein with a reasonable expectation of similar success. Prior to the effective filing date of the claimed invention, marigold flowers were a known source for lutein as taught by Khachik. Khachik teaches a method of isolating, purifying and recrystallizing substantially pure lutein, preferably from saponified marigold oleoresin in its pure free form, apart from chemical impurities and other carotenoids (abstract). Thus, preparing lutein based on the procedure of Khachik would have been seen as an obvious solution within the skill of an ordinary artisan practicing the invention of Yeum.
Applicant argues that the claimed invention relates to a dietary supplement comprising lutein extracted from marigold and natural tocopherols derived from sunflower. The formulation is non-GMO, free of soy, marine, or animal-based components, and is stabilized using sunflower-derived vitamin E (not synthetic d-α- tocopherol). The primary claim is that such a composition, when administered orally, protects against telomere shortening under oxidative stress, as a biomarker of aging. Applicant argues that they have conducted an in vitro study using human primary dermal fibroblasts under oxidative stress (10 µM H₂O₂), with 1, 5, and 10 µg/mL Lute-gen® doses. Telomere length was measured using HT Q-FISH (Telomere Analysis Technology by Life Length) - a highly precise and validated method. Key findings after 8 passages (8 weeks) is noted below: Significant reduction in telomere shortening rate at all tested doses (p < 0.05 to p < 0.001). Improved preservation of median telomere length and reduced % of short telomeres. Effect observed even at low dose (1 µg/mL), indicating strong and potentially synergistic activity.
These arguments are found not persuasive since there is no requirement in the instant claims that the tocopherols are derived from sunflower. Claim 1 of the instant application claims a method of reducing, ameliorating, preventing, or reversing oxidative DNA damage in a human being, comprising orally administering an effective dose of a dietary supplement composition comprising natural lutein and tocopherols, optionally along with acceptable additives, wherein the natural lutein is derived from marigold flowers, wherein the amount of the tocopherols in the dietary supplement composition is in the range of 0.1 to 10 weight-%, wherein the dietary supplement composition does not comprise any of the following compounds: hydrolyzed lecithin products, lactose-based products, animal-based products, soy- based products or marine-based products, wherein the dietary supplement composition reduces, ameliorates, prevents, or reverses the oxidative DNA damage and slows the rate of telomere shortening in vitro by at least 20%. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., tocopherol derived from sunflower) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Yeum specifically teaches the supplement can contain other active compounds including, but not limited to the following compounds: Fat-soluble vitamins, such as vitamin E and derivatives [0041]. Yeum further specifically teaches to increase the stability of the active compounds to oxidative degradation, it can be advantageous to add from 0 to 10% by weight, preferably from 0.5 to 7.5% by weight, based on the dry matter of the formulation, of one or more stabilizers, such as alpha-tocopherol [0052]. Yeum further teaches Vitamin E in this context is natural or synthetic alpha-, beta-, gamma- or delta-tocopherol, preferably natural or synthetic alpha-tocopherol, or else is tocotrienol [0041]. Thus Yeum specifically teaches the use of natural tocopherol in overlapping amounts for the same purpose as argued by Applicant which is to stabilize the composition.
Applicant argues that Yeum discloses co-administration of lutein and tocopherols for antioxidant effects but does not mention telomeres, telomerase, or telomere preservation. The Examiner assumes that telomere protection is an expected result of antioxidant activity. However Applicant argues that many antioxidants do not confer telomere protection, especially not in validated human models. Telomere protection is not an inherent or inevitable result of antioxidant supplementation. This is supported by published literature showing that many antioxidants do not prevent telomere shortening, and in some cases, can have no measurable effect in validated models. Thus Applicant argues that the observed effect is therefore not a latent property but an unexpected, experimentally demonstrated outcome. Yeum provides no experimental evidence or suggestion of telomere-related endpoints. The results noted in the instant specification were not additive or linear, indicating synergy that would not have been obvious.
These arguments are found not persuasive because the Examiner does not assume that telomere protection is an expected result of antioxidant activity, rather the basis of the rejection is that telomere protection is an effect that will necessarily occur as a result of practicing the method of Yeum and administering the lutein composition for decreasing DNA damage and/or for use in protecting against a free radical associated disorder wherein an effective daily dose of lutein is about 0.1 to 20 mg, preferably 2 to 10 mg per day ([0010] and [0030]). Thus since Yeum renders obvious the administration of the same combination of components as claimed for the same purpose of reducing oxidative DNA damage, the method of Yeum will necessarily also have the same effect as claimed which is to slow telomere shortening. It is not necessary that the prior art suggest the same advantage or result discovered by applicant when the steps of the claim are the same as those described or suggested by the prior art. See, e.g., In re Kahn, 441 F.3d 977, 987 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. V. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323 (Fed. Cir. 2005) ("One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings."); In re Lintner, 458 F.2d 1013 (CCPA 1972); In re Dillon, 919 F.2d 688 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991). Here, the prior art renders obvious the same method as claimed which is reducing oxidative DNA damage comprising the administration of a dietary supplement comprising lutein and tocopherol. The mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Prindle, 297 F.2d 251, 254 (CCPA 1962). Here, the latent property identified by Applicant is slowing the rate of telomere shortening which will necessarily occur in the prior art by following the teachings and suggestions of the prior art and administering a dietary supplement containing lutein and tocopherol.
With regard to claim 2 of the instant application, Applicant notes that lutein is a highly unstable compound, susceptible to degradation from: Light, Heat, Oxygen exposure, and Low pH. Therefore, the manufacturing process - including saponification, crystallization, and stabilization with tocopherols - is crucial to ensure the biological activity and stability of the product. Applicant argues that this process control, as detailed in the patent specification and recited in presented claim 2, is essential to delivering the claimed biological benefits (telomere protection) and is not taught or suggested by the cited prior art. Applicant argues that Khachik does not disclose, teach, or suggest several features of presented claim 2. Applicant argues the claimed process is designed to extract lutein from Tagetes erecta (marigold) to yield high-purity lutein crystals, with a standardized lutein content and after crystallization, natural tocopherols are added as stabilizers, which is critical due to the high sensitivity of lutein to heat, light, and oxidation. Applicant argues that Khachik merely lists marigold but does not teach the specific combination of process parameters
(controlled saponification, cold recrystallization, vacuum drying, post-purification tocopherol stabilization) that are essential for stability and bioactivity. Applicant argues that while Khachik lists Tagetes erecta among possible sources of carotenoids, it does not teach the specific, stability-focused process steps recited in claim 2 - including controlled saponification, cold recrystallization, vacuum drying, and post-purification tocopherol stabilization - which are essential to achieving the claimed biological outcome. In addition, Applicant argues that Khachik does not mention tocopherols used for stabilization, and on the contrary, focus in Khachik is on pigment isolation and purification and stability measures are not clearly disclosed. Applicant argues the claimed process is designed not just for yield but to ensure biological efficacy, as proven by telomere protection data. Thus Applicant argues that Khachik aims at pigment extraction and identification and does not provide any link to biological endpoints like telomere protection or activity.
These arguments are found not persuasive because Khachik specifically teaches the addition of a-tocopherol (0.01% by weight) was to stabilize lutein and prevent this compound from possible oxidation during long term storage. See Example 3 column 8. Thus Khachik is concerned with product stability since Khachik specifically teaches the addition of a-tocopherol (0.01% by weight) to stabilize lutein and prevent this compound from possible oxidation during long term storage. Moreover, as detailed in the rejection of record Khachik teaches a similar method to prepare lutein including saponification, cold recrystallization, vacuum drying, and post-purification tocopherol stabilization (see Examples 1-3 columns 5-8). Applicant has not provided any evidence that their process for producing lutein is critical. Applicant has not compared their process of preparing lutein with any other process and demonstrated better results utilizing lutein produced by their process. Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.").
In addition, even 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. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). See MPEP 2113. “The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature” than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an unobvious difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 798, 802, 218 USPQ 289, 292 (Fed. Cir.1983). See MPEP 2113. Thus, because Applicant has not provided any evidence that the lutein produced by the claimed method is any different from the lutein produced by the method of Khachik, and moreover has not provided any evidence of criticality, Applicant’s arguments are found not persuasive. Thus it is maintained that Khachik discloses a process for preparing lutein which is known in the art and thus an ordinary skilled artisan would have been motivated to prepare the lutein of Yeum based on this known procedure to arrive at the instant invention with a reasonable expectation of success.
Thus, for reasons of record and for the reasons detailed above, the previous rejection under 35 USC 103 is hereby maintained, however the rejections have been combined into one rejection in view of Applicant’s amendments to the claims. This action is NON-Final.
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-11, 15 and 18-21 are rejected under 35 U.S.C. 103 as being unpatentable over Yeum U.S. Publication No. 2007/0082044 A1 in view of Khachik U.S. Patent No. 5,382,714.
Claims 1-11, 15 and 18-21 of the instant application claim a method of reducing, ameliorating, preventing, or reversing oxidative DNA damage in a human being, comprising orally administering an effective dose of a dietary supplement composition comprising natural lutein and tocopherols, optionally along with acceptable additives, wherein the natural lutein is derived from marigold flowers, wherein the amount of the tocopherols in the dietary supplement composition is in the range of 0.1 to 10 weight-%, wherein the dietary supplement composition does not comprise any of the following compounds: hydrolyzed lecithin products, lactose-based products, animal-based products, soy-based products or marine-based products, wherein the dietary supplement composition reduces, ameliorates, prevents, or reverses the oxidative DNA damage and slows the rate of telomere shortening in vitro by at least 20%. Claims 2-4 of the instant application further claim the dietary supplement composition comprising natural lutein is produced by a method comprising a. saponifying Marigold Oleoresin (Tagetes erecta) in the presence of an alcohol or organic solvent and an alkali for about 2 hours at a preferable temperature of about 80 to 85 degrees centigrade; b. adding an aqueous solution to the reaction mass, thereby obtaining a neutralized mass; c. filtering the neutralized mass, to obtain the Lutein crystals; d. further crystalizing the Lutein crystals in the presence of alcohol at 5 degrees centigrade to obtain a purity of 75% to 80% Lutein; e. stabilizing the Lutein crystals by adding natural tocopherols, and maintaining at room temperature; and f. vacuum drying the 75% to 80% purity Lutein crystals for about 2 hrs.
Yeum teaches that oxidative stress has been implicated in the pathogenesis of chronic diseases related to aging, such as cancer and cardiovascular disease and numerous epidemiological studies have indicated that diets rich in fruits and vegetables are correlated with a reduced risk of such diseases [0001]. Yeum teaches that it is believed that the antioxidants present in the fruits and vegetables can prevent damage from harmful reactive oxygen species, which are continuously produced in the body during normal cellular functioning and thus, a diet supplemented with antioxidants can be a part of a defense strategy to minimize oxidative damage in a vulnerable population such as the elderly [0001]. Yeum teaches that carotenoids, naturally-occurring pigments which are synthesized by plants, algae, bacteria, and certain animals, such as birds and shellfish have antioxidant activities [0002]. Carotenoids are a group of hydrocarbons (carotenes) and their oxygenated, alcoholic derivatives (xanthophylls) and include, carotene, lutein, lycopene, and zeaxanthin, and as a result of a high intake of fruits and vegetables, 34 carotenoids and their metabolites are found in human serum and tissues at varying concentrations, wherein a-carotene, b-carotene, lycopene, lutein, b-cryptoxanthin, and zeaxanthin are the predominant carotenoids found in plasma [0002].
Yeum teaches methods of decreasing DNA damage through the administration of a carotenoid supplement [0005]. Yeum teaches the methods of the invention can be used to protect against certain disorders that arise from oxidative stress and the presence of excess free radicals in a subject [0005]. Yeum teaches in one aspect, the invention pertains to a method of decreasing DNA damage through the administration of a combination of carotenoids wherein the combination of physiological doses of lutein, b-carotene and lycopene has a synergistic effect resulting in a decrease of DNA damage that exceeds that of carotenoids given alone [0006]. Yeum teaches in another aspect, the combination of physiological doses of lutein, b-carotene and lycopene changes the antioxidant capacity in the aqueous and lipid compartments of plasma and improves DNA response to an oxidative stress [0007]. DNA is less susceptible to oxidative damage following supplementation of the mixture of lutein, with at least one of b-carotene and/or lycopene [0007].
Yeum teaches in some embodiments, the method can be practiced using a carotenoid-containing dry powder in the form of a multicore structure in which at least two cores of a multicore structure comprise one or more different carotenoids selected from the group consisting of substantially purified lutein, beta-carotene, and lycopene [0008]. Yeum teaches in some embodiments, the invention comprises administering a carotenoid-containing dry powder in different forms, such as drink preparations, tablets, sugar coated tablets and hard and soft gelatin or cellulose capsules [0008].
Yeum teaches a pharmaceutical composition for use in decreasing DNA damage and/or for use in protecting against a free radical associated disorder comprising an effective daily dose of about 0.1 to 20 mg lutein, and at least one of the group consisting of beta-carotene and lycopene in an amount sufficient to act synergistically with lutein, [0010]. The composition can further comprise at least one of about 0.1 mg to 20 mg beta-carotene or about 0.1 to 20 mg lycopene, or about 0.5 mg to 10 mg beta-carotene or about 0.5 to 10 mg lycopene [0010]. The composition can further comprise a carotenoid-containing dry powder in the form of a multicore structure in which at least two cores of a multicore structure comprise one or more different carotenoids of the group consisting of substantially purified lutein, beta-carotene, and lycopene [0010]. The carotenoid-containing dry powder can be made into different forms, including, but not limited to, drink preparations, tablets, sugar coated tablets, hard gelatin capsules and soft gelatin capsules [0010].
Yeum further teaches a method of slowing the effects of aging by administering a synergistic combination of carotenoids to the subject, wherein the synergistic combination comprises at least two of the group consisting of lutein, beta-carotene, and lycopene [0012]. Yeum teaches the present composition can reduce DNA damage, thereby slowing the effects of the aging process [0012].
Yeum teaches subject includes, but is not limited to, humans, nonhuman primates such as chimpanzees and other apes and monkey species; farm animals such as cattle, sheep, pigs, goats and horses; domestic mammals such as dogs and cats; laboratory animals including rodents such as mice, rats and guinea pigs, and the like [0022].
Yeum teaches Lutein can be obtained from green leafy vegetables, b-carotene is present in yellow and orange vegetables, and lycopene is predominantly contained in tomatoes [0027]. The synergistic effect of these carotenoids result in a protective effect against free-radical associated disorders and oxidative stress and the combination of these carotenoids has been shown to decrease DNA damage [0027]
Yeum teaches that Lutein and zeaxanthin are polar carotenoids, while beta-carotene and lycopene are non-polar carotenoids [0028]. Lycopene, a red-pigmented carotenoid which can be found, for example, in tomatoes comprises a long chain of conjugated double bonds, which give lycopene its ability to neutralize free radicals, in particular, lycopene is a powerful neutralizer of superoxide (O2) [0028]. Beta-carotene consists of a long nonpolar chain and will therefore be located in cell membranes and lipoproteins and Lutein is a natural fat-soluble yellowish pigment the structure of which contains hydroxyl groups; Lutein's polar structure allows it to anchor to and span the membrane, which increases membrane rigidity, while non-polar beta-carotene and lycopene can cross into the membrane [0028].
Lutein and zeaxanthin belong to the xanthophyll class of carotenoids, also known as oxycarotenoids and can be found in corn, egg yolks and green vegetables and fruits, such as broccoli, green beans, green peas, brussel sprouts, cabbage, kale, collard greens, spinach, lettuce, kiwi and honeydew [0029]. Yeum teaches that although lutein and zeaxanthin have identical chemical formulas and are isomers, they are not stereoisomers, they are both polyisoprenoids containing 40 carbon atoms and cyclic structures at each end of their conjugated chains [0029]. Yeum teaches that "lutein" is intended to include lutein and all its isomers, including zeaxanthin [0029].
Yeum specifically teaches a method of decreasing DNA damage through the administration of a combination of carotenoids, wherein the combination of physiological doses of lutein, b-carotene and lycopene have a synergistic effect resulting in a decrease of DNA damage that exceeds that of carotenoids given alone [0030]. The carotenoid content can range from 0.1 to 20 mg of beta-carotene, from 0.1 to 20 mg of lycopene and 0.1 to 20 mg of lutein, preferably from 0.5 to 10 mg of beta-carotene, from 0.5 to 10 mg of lycopene and from 0.5 to 10 mg of lutein, particularly preferably from 2 to 10 mg of beta-carotene, from 2 to 10 mg of lycopene and from 2 to 10 mg of lutein [0030].
Yeum further teaches stable, homogeneous equal distribution of active compounds can be enhanced by administering the compounds in the form of a multicore structure in which at least two cores of a multicore structure comprise one or more different carotenoids of the group consisting of substantially purified lutein, beta-carotene, and lycopene [0037]. The multicore structure is a particle species having a mean particle size of from 5 to 3000, preferably from 10 to 2500 mm, particularly preferably from 50 to 2000 mm, very particularly preferably from 100 to 1000 mm [0037].
Yeum teaches the preferred supplement comprises a mixture of beta-carotene, lycopene and lutein, however, the supplement can contain other active compounds suitable for the food sector and animal nutrition sector or for pharmaceutical and cosmetic applications including, but not limited to the following compounds: Fat-soluble vitamins, for example the K vitamins, vitamin A and derivatives such as vitamin A acetate, vitamin A propionate or vitamin A palmitate, vitamin D2 and vitamin D3 and vitamin E and derivatives [0041]. Vitamin E in this context is natural or synthetic alpha-, beta-, gamma- or delta-tocopherol, preferably natural or synthetic alpha-tocopherol, or else is tocotrienol [0041]. Yeum further teaches additional carotenoids, not only carotenes but also xanthophylls, for example zeaxanthin may be included [0041].
Yeum teaches that Lutein has a purity of at least 75%, preferably greater than 80%, particularly preferably greater than 85% and in the case of carotenoids from natural sources, for example lutein or lycopene, it is possible that these compositions can comprise up to 20% of other carotenoids, for example zeaxanthin [0042].
Yeum teaches the content of beta-carotene, lycopene and lutein in the inventive dry powders is generally from 0.1 to 50% by weight, preferably from 1 to 35% by weight, particularly preferably from 3 to 25% by weight, very particularly preferably from 5 to 20% by weight, based on the total amount of the formulation [0044].
Yeum specifically teaches to increase the stability of the active compounds to oxidative degradation, it can be advantageous to add from 0 to 10% by weight, preferably from 0.5 to 7.5% by weight, based on the dry matter of the formulation, of one or more stabilizers, such as alpha-tocopherol [0052].
Yeum further teaches the carotenoid formulations are suitable, as additives for food preparations, in particular drink preparations, as agent for producing pharmaceutical and cosmetic preparations and for producing food supplement preparations in the human and animal sectors [0059]. It is also possible to use dry powders which comprise the inventive carotenoid combinations to enrich milk products such as yogurt, flavored milk drinks or ice cream, or milk pudding powders, baking mixes and confectionery products, for example fruit gums [0060]. Yeum teaches food supplements, animal feeds, foods and pharmaceutical and cosmetic preparations comprising the carotenoid formulations of mixtures of beta-carotene, lycopene and lutein [0061]. Food supplement preparations and pharmaceutical preparations which comprise the inventive dry powders include, but are not limited to, tablets, sugar-coated tablets and hard and soft gelatin capsules [0061]. These capsules contain 0.1 to 20 mg of lutein, preferably from 1 to 10 mg of lutein, particularly preferably from 2 to 10 mg of lutein [0061].
Claims 1-20 of Yeum specifically claim a pharmaceutical composition for use in decreasing DNA damage comprising an effective daily dose of about 0.1 to 20 mg lutein, and at least one of the group consisting of beta-carotene and lycopene in amounts sufficient to act synergistically with lutein, as well as a method of decreasing oxidative damage in a subject as well as reducing effects of aging in a subject comprising: administering a synergistic combination of carotenoids to the subject, wherein the synergistic combination comprises at least two carotenoids selected from the group consisting of lutein, beta-carotene, and lycopene.
Yeum does not teach that the dietary supplement composition comprises any of the following compounds: hydrolyzed lecithin products, lactose-based products, animal-based products, soy-based products or marine-based products as excluded in the instant claims.
Yeum does not specifically exemplify a formulation comprising 0.1 to 10 weight% of tocopherols. Yeum does not teach that the natural lutein is derived from marigold flowers. Yeum does not teach the process for preparing lutein as claimed.
Although Yeum does not specifically exemplify a formulation comprising 0.1 to 10 weight% of tocopherols, Yeum specifically teaches the supplement can contain other active compounds including, but not limited to the following compounds: Fat-soluble vitamins, such as vitamin E and derivatives [0041]. Yeum further specifically teaches to increase the stability of the active compounds to oxidative degradation, it can be advantageous to add from 0 to 10% by weight, preferably from 0.5 to 7.5% by weight, based on the dry matter of the formulation, of one or more stabilizers, such as alpha-tocopherol [0052].
Accordingly, prior to the effective filing date of the claimed invention, it would have been prima facie obvious to add 0.5 to 7.5% by weight, based on the dry matter of the formulation, of alpha-tocopherol to the formulation of Yeum comprising lutein and one or more of beta-carotene and lycopene to increase stability of the active compound and prevent oxidative degradation. Moreover, a person of ordinary skill in the art would have been specifically motivated to include alpha-tocopherol to the formulation of Yeum as a stabilizer since Yeum also teaches that vitamin E (tocopherol) can also act as an active ingredient suitable for combining with lutein. Thus a method for reducing oxidative DNA damage in a human being comprising the administration of a dietary supplement composition comprising natural lutein and 0.5 to 7.5% by weight of tocopherol to a human being is rendered obvious in view of the teachings of Yeum.
Although, Yeum does not teach the process for preparing lutein from marigold flowers as claimed, please note that even 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. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). See MPEP 2113.
In addition, it would have been obvious to a person of ordinary skill in the art to prepare the components for use in the method of Yeum by any suitable method known in the art.
Khachik teaches a method of isolating, purifying and recrystallizing substantially pure lutein, preferably from saponified marigold oleoresin in its pure free form, apart from chemical impurities and other carotenoids (abstract).
Khachik teaches that Saponified marigold oleoresin (derived from dried marigold flowers (Tagetes erecta) column 3 line 67-column 4 line 1) available commercially as "Kemin Yellow Oil" was obtained, wherein it was previously processed in the following manner: The oleoresin extract (200 g) was then subjected to saponification with aqueous potassium hydroxide through continuous mixing under heat (65°-70° C) of food grade aqueous potassium hydroxide (45%) and the oleoresin until greater than 98% of lutein was free from fatty acid esters. The saponification was normally completed within 35 minutes. The product was then homogenized with a mixture of distilled water (700 mL)/ethanol (300 mL, food grade):2.3/1 at room temperature for 30 minutes. The mixture was filtered off and the filtrate was discarded. The retained orange precipitate of lutein was washed with distilled water until the filtrate was almost colorless and the pH was neutral. The precipitate was then washed sequentially with cold (0°C.-5°C.) ethanol (200 mL) and hexane (200 mL), respectively. The resulting lutein obtained as orange crystals from three to be 70% pure by spectrophotometric analysis. Final purification was accomplished by recrystallization from a 1:1 mixture of dichloromethane and hexane by dissolving the 70% pure crystals in about 550 ml of dichloromethane containing 1% of triethylamine. The hexane was added until the solution became cloudy. The cloudy solution was kept at -20°C. to -10°C. to commence recrystallization. This was completed within about 3 hours resulting in orange crystals of lutein. The crystals were then filtered off and washed with cold (0°C) hexane (200 ml) and dried in vacuo at 50°C. for 3 days. The purity of lutein in this instance was greater than 97%. See Example 1 columns 5-6.
Khachik further teaches that the Saponified marigold oleoresin (200 g) was homogenized with a mixture of distilled water/ethanol (food grade) at various ratios at 0°C-10°C for 30 minutes. The mixture was filtered off and the filtrate was discarded. The retained orange precipitate of lutein was washed with distilled water until the filtrate was almost colorless and the pH was neutral. The precipitate was then washed sequentially with cold (0°C-5°C) ethanol (200 mL) and hexane (200 mL), respectively. The lutein obtained in all three experiments was shown to be about 70% pure by spectrophotometric analysis. See Example 2 column 6.
Khachik further teaches the preparation of a lutein dose for oral supplementation comprising using the purified lutein as described above from marigold flowers extract (1 g) was added to absolute alcohol (75 mL). To this solution a-tocopherol (50 mg) and food grade polysorbate 80 (an emulsifier, 4 g) was added and the mixture was sonicated for 10 minutes. The addition of a-tocopherol (0.01% by weight) was to stabilize lutein and prevent this compound from possible oxidation during long term storage. The above suspension was then mixed with 350 g of light and mild olive oil (saturated fat/polyunsaturated fat=2/1) and the mixture was sonicated for 5 minutes. This resulted in a suspension of lutein in olive oil which was stored under nitrogen in a refrigerator. See Example 3 column 8.
Thus Khachik teaches a similar method as claimed for preparing lutein.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art practicing the invention of Yeum, to use any process known in the art to obtain a suitable lutein product. Khachik teaches a process which produces substantially pure lutein which contains small amount of acceptable impurities such as zeaxanthin. Thus an ordinary skilled artisan would have been motivated to use said process with a reasonable expectation of success. Thus claims 2-4 are rendered obvious in view of the cited prior art teachings.
Thus since Yeum renders obvious the administration of the same combination of components as claimed for the same purpose of reducing oxidative DNA damage, the method of Yeum will necessarily also have the same effect as claimed which is to slow the rate of telomere shortening in vitro by at least 20%.
Claim 9 which claims granules having a particle size distribution in the range of 20 mesh to 100 mesh which is equivalent to 841 mm to 149 mm is rendered obvious since Yeum teaches a dry powder having a mean particle size of from 5 to 3000 mm, preferably from 10 to 2500 mm, particularly preferably from 50 to 2000 mm, very particularly preferably from 100 to 1000 mm [0037].
Claim 11 of the instant application is rendered obvious since Yeum further teaches additional carotenoids, not only carotenes but also xanthophylls, for example zeaxanthin may be included [0041]. Yeum teaches that Lutein has a purity of at least 75%, preferably greater than 80%, particularly preferably greater than 85% and in the case of carotenoids from natural sources, for example lutein or lycopene, it is possible that these compositions can comprise up to 20% of other carotenoids, for example zeaxanthin [0042]. Thus the formulation of Yeum may contain a molar ratio of lutein to zeaxanthin in the range of 20:1 to 1:1 as claimed in claim 11.
Claim 15 is rendered obvious since Yeum teaches that the dietary supplement is for human consumption and thus necessarily has the properties (safe and non-toxic and free of adverse effects) as claimed in claim 15. Moreover, Yeum does not teach the addition of any of the components (gluten, solvent, pesticide or aflatoxin) as claimed in claim 15.
Claims 18 and 19 are rendered obvious since Yeum teaches a daily unit dose of about 0.1 mg to 20 mg beta-carotene, about 0.1 to 20 mg lycopene, and about 0.1 to 20 mg lutein to the subject (claim 9). Thus Yeum teaches administration of a daily amount of lutein (0.1 to 20 mg) which overlaps with the claimed effective dose of 6 mg to 10 mg as claimed. Thus the method of Yeum will necessarily have the same results of reducing oxidative DNA damage by at least 20% as compared to a subject not administered the effective dose of lutein as claimed in claim 18. Moreover, claim 18 is rendered obvious since Yeum specifically teaches administering the composition to reduce oxidative DNA damage, and therefore it would have been obvious to a person of ordinary skill in the art to administer a suitable amount of lutein such that oxidative DNA damage is reduced as much as possible.
Thus the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Conclusion
Claims 1-11, 15 and 18-21 are rejected. Claim 12-14, 16 and 17 are canceled. No claims are allowed.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM
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