Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
2. This Office Action is responsive to Applicant’s Amendment and Remarks, filed November 26, 2025, wherein there is no amendment to the claims.
Claims 1 – 2, 4, 9 – 12 – 19, 21 – 23, and 25 are pending in this application, wherein claims 12 – 19, 21 – 23, and 25 are withdrawn, and claims 3, 5 – 8, 10 – 11, 20, 24, and 26 – 27 are canceled.
Priority
This application is a continuation application of 16/299,9665, filed March 12, 2019, now issued as U.S. Patent No. 11,147,784, which is a continuation of 14/901,859, filed December 29, 2015, now abandoned, which is a national stage application of PCT/US14/45168, filed July 1, 2014, which claims benefit of domestic application 61/841,806, filed July 1, 2013.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 61/841,806, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The domestic application 61/841,806 does not provide support for the limitations of “substantially devoid of glycine” and/or “the molar ratio of homocysteine to methionine in the supplement is about 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 20:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1, or 100:1” recited in claims 1 – 2, 4, and 9. Thus, the priority date of claims 1 – 2, 4, and 9 is July 1, 2014.
Withdrawn Objections
4. The objection to the drawings, figures 2C, 2D, and 3A, in the previous Office Action, mailed May 29, 2025, under 37 CFR 1.83(b) is withdrawn in view of the amended figures.
Withdrawn Rejections
5. The rejection of claims 1 – 2, 4, and 9 in the previous Office Action, mailed May 29, 2025, under 35 U.S.C. 103 as being unpatentable over Hoffman in view of Poupon et al. has been considered and is withdrawn in view of Applicant’s argument regarding Hoffman only describes media with or without methionine or homocysteine.
The followings are maintained / modified / new grounds of rejection necessitated by Applicant’s Amendment and Remarks, filed November 26, 2025, wherein no claim has been amended. Previously cited references are used to establish the maintained / modified / new grounds of rejection.
Maintained / Modified 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 1 – 2, 4, and 9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (e.g. a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The claims recite a nutritional or pharmaceutical composition comprising a mixture of amino acids, including methionine and homocysteine, which is a natural product.
Step 1: Claims 1 – 2, 4, and 9 recite compositions of matter, thus, the claims fall into a statutory category of invention under 35 U.S.C. 101.
Step 2A1: The claimed nutritional supplement comprises an amino acid mixture of homocysteine and methionine, which are naturally occurring compounds that are known in the art. When, as here, a claim recites a nature-based product limitation, examiners should use the markedly different characteristics analysis discussed in MPEP § 2106.04(c) to evaluate the nature-based product limitation.
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 in terms of structure, function, and/or other properties, and are evaluated on what is recited in the claim. 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).
Claiming a natural product that is merely separated from elements found in its natural environment, where the structure of the natural product is not otherwise altered, does not support a conclusion that the isolated product is patent eligible. Ass’n for Molecular Pathology v. Myriad, 569 U.S. 576 at 593-5 (2013) (contrasting cDNA, which is exons-only molecule that is not naturally occurring, from isolated DNA segments because the isolated DNA segments do not contain altered genetic information compared to the gene from which isolated, notwithstanding that the isolated DNA segment was obtained by breaking chemical bonds).
The courts have emphasized that to show a marked difference, a characteristic must be changed as compared to nature, and cannot be an inherent or innate characteristic of the naturally occurring counterpart or an incidental change in a characteristic of the naturally occurring counterpart. Myriad, 569 U.S. 576 at 580, 106 USPQ2d at 1974-75. Thus, in order to be markedly different, the Applicant must have caused the claimed product to possess at least one characteristic that is different from that of the counterpart.
The first step in the analysis requires selecting the appropriate natural counterparts to the claimed nature-based products. The appropriate natural counterpart to the claimed nutritional supplement are the same amino acids as found in their natural state. The second step in the analysis requires identifying appropriate characteristics to compare. In this case, the appropriate characteristics pertain to the chemical nature of the compounds, which ultimately determine their bioactivity.
The analysis requires determining if the claimed nutritional supplement results in these amino acids having structural, functional, or other properties that are different from these amino acids as found in their natural setting. While the specification stating that the claimed nutritional supplement possess certain bioactivity (para. [0098]), this activity is based on the alteration of amino acids level . No actual evidence or data is provided to asserted that the alteration of amino acids level changes the intrinsic bioactivity of the claimed compounds.
Claims 1 – 2, 4, and 9 require the nutritional supplement comprising an amino acid mixture, wherein the mixture comprises a molar ratio of homocysteine to methionine greater than 1. Where a claim is directed 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 (MPEP 2106.04(c)(I)(A), unless the combination cannot be found in nature, in which case the closest counterpart may be the individual nature-based components of the combination. (MPEP 2106.04(c)(II)(A). 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. See, e.g., Funk Bros., 333 U.S. at 130, 76 USPQ at 281 (comparing claimed mixture of bacterial species to each species as it occurs in nature); Ambry Genetics, 774 F.3d at 760, 113 USPQ2d at 1244 (although claimed as a pair, individual primer molecules were compared to corresponding segments of naturally occurring gene sequence). Id. In this case, there is again no evidence presented indicating that the inclusion of these amino acids alters the chemical nature or intrinsic bioactivity of these amino acids.
Accordingly, claims 1 – 2, 4, and 9 recite judicial exceptions, i.e., products of nature.
Step 2A2: This part of the eligibility analysis evaluates whether a claim as a whole integrates the recited judicial exception into a practical application. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. A claim reciting a judicial exception is not directed to the judicial exception if it also recites additional element(s) demonstrating that the claim as a whole integrates the exception into a practical application. One way to demonstrate such integration is when the additional elements apply or use the recited judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. The application or use of the judicial exception in this manner meaningfully limits the claim by going beyond generally linking the use of the judicial exception to a particular technological environment, and thus transforms a claim into patent-eligible subject matter. In order to qualify as a "treatment" or "prophylaxis" limitation for purposes of this consideration, the claim limitation in question must affirmatively recite an action that effects a particular treatment or prophylaxis for a disease or medical condition. An example of such a limitation is a step of "administering amazonic acid to a patient" or a step of "administering a course of plasmapheresis to a patient." If the limitation does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception under the "treatment or prophylaxis" consideration. (MPEP 2106.04(d)(2)).
Each of claims 1 – 2, 4, and 9 are drawn to compositions which do not include limitations imposing any particular use of or application of the claimed judicial exceptions, such as a particular treatment or prophylaxis. Accordingly, the compositions of claims 1 – 2, 4, and 9 do not contain additional elements that result in a practical application of the claimed nutritional supplement, because these claims are drawn to compositions rather than applications of the compositions.
Step 2B: This part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim.
The search for an “inventive concept” as required by the Supreme Court in Alice is not the search for a “patentable invention” (which includes satisfying §§ 102, 103 and 112, in addition to 101). An inventive concept "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself." Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016). See also Alice Corp., 573 U.S. at 21-18, 110 USPQ2d at 1981. Instead, an "inventive concept" is furnished by an element or combination of elements recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself. Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966).
In this case, the claimed judicial exceptions occur within nutritional supplement (claims 1 – 2 and 4) and pharmaceutical compositions (claim 9). Formulating amino acids into such compositions represents well-understood, routine, and conventional practice. For example, Poupon et al. (US5208039, cited in the previous Office Action) teaches the composition of the invention comprising a source of amino acids lacking in methionine, with the missing methionine being replaced with homocysteine (Col. 3, lines 8 – 10). Homocysteine is added as a replacement for the methionine, that is that the homocysteine content corresponds, in molar equivalents, to the lack of methionine (Col. 2, lines 3 – 6). The composition formulated for human contains a methionine content reduced by x %, with x being at least 50 (Col. 11, lines 3 – 4, claim 1). In a similar manner that taught in Example 1, various compositions were prepared for mice or rats, cats, dogs, or man, lacking approximately 75% of the methionine and with no disclosure regarding the amount of glycine (Col. 3, lines 49 – 51). Moreover, Poupon et al. teaches that the composition will generally be an additional treatment associated with other methods of therapy such as chemotherapy or radiotherapy. The treatment can be continued, for example, for 1 to 4 months. In example 1, methionine content is reduced by 75%. This means the same amount of homocysteine will be used to replace the lacking methionine. Based on the calculation, the molar ratio of homocysteine and methionine is 3:1.Amelio et al. (Trends in Biochemical Sciences, April 2014, Vol. 39, Issue 4, page 191 – 198, Reference included with PTO-892) disclose that glycine can be directed to the biosynthesis of purines, where it provides two carbon atoms and a nitrogen atom in the purine ring (page 195, Left Col., para. 2) and disclose some studies, which confirm that glycine deprivation may be a new route for human cancer chemotherapy (page 195, Right Col., para. 1 – 2).
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed November 26, 2025, have been fully considered and are found to be not persuasive.
Applicant argues that the claims are directed to a product made by human intervention that is not necessarily found in nature or directed to a natural product. However, to determine whether a claim is directed to a judicial exception, it is necessary to evaluate the claimed invention as a whole recites a law of nature, a natural phenomenon, or an abstract idea. The claims are still directed to a judicial exception if the focus of the claims is on a natural product or a natural phenomenon, regardless of whether the exact combination is found in nature. The primary elements themselves are naturally occurring products, As such, the invention as a whole would still be directed to a judicial exception under step 2A, Prong 1, because it is focused on naturally occurring substances.
Applicant argues that the composition must be taken as a whole and not divided into its part to determine its eligibility. The examiner acknowledges the argument and would like to point out that the claimed invention has been considered as a whole as well as dividing into its part. Following the Steps and Prongs, it is clear that the composition is taken as a whole when determining the markedly different characteristics. In order to be markedly different, Applicant must have caused the claimed product to possess at least one characteristic that is different from that of the natural counterpart. However, there is no evidence presented in the specification or otherwise found in the art suggesting that the claimed composition would possess structural and/or functional differences in chemical constituency as compared to its natural counterpart components. The combination of natural products does not, by itself, circumvent the finding that the claim is drawn to a judicial exception, when there is no evidence of a marked differences resulting from the combination. Because there is no demonstrated change in any characteristic, the claimed composition lacks markedly different characteristics from its natural ingredients, and is a product of nature exception.
Applicant argues that the alteration of amino acid levels would impair cancer growth. However, such alteration does not yield unexpected results as Poupon et al. already teach a composition of amino acid mixture with 3:1 homocysteine and methionine for the purpose of cancer treatment and Amelio et al. teach that glycine would fuel cancer cells. Therefore, it is expected that the amino acids composition without glycine will affect cancer growth.
Applicant argues that the claims are judicial exception that has practical application because the present composition is a nutritional supplement that is useful in the treatment of cancer. However, the Step 2A, Prong 2 is based on the language of the claims itself. While the specification may describe a therapeutic use, the claims do not recite any treatment step or functional language indicating such use.
Applicant argues that the claims taken as a whole amount to significantly more than the recited exception because the composition contain a change in normal ratios of the amino acids that alter the way the metabolic pathways work. However, formulating amino acids into such compositions represents well-understood, routine, and conventional practice. As mentioned above, Poupon et al. already teach a composition with a modification on the levels of homocysteine and methionine and Amelio et al. teach the effect of glycine. A skilled artisan would be able to modify the level of glycine under well-understood, routine, and conventional practice to achieve the claimed formulation.
Finally, Applicant argues that the examiner fails to consider the lack of preemption associated with the claimed invention. However, preemption is not a separate test for eligibility, a claim can be ineligible even if it does not entirely preempt all applications of a judicial exception. In this case, the claims are directed to composition comprising naturally occurring amino acids in a specific ratio, and lacks any additional elements that integrate the natural product into a practical application or amount to significantly more than the judicial exception. Accordingly, the claim remains ineligible under 35 U.S.C. 101.
Modified / New 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. Considering objective evidence present in the application indicating obviousness or
nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 – 2, 4, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Poupon et al. (US5208039, cited in the previous Office Action) in view of Amelio et al. (Trends in Biochemical Sciences, April 2014, Vol. 39, Issue 4, page 191 – 198, Reference included with PTO-892).
a. Regarding claims 1 – 2, 4, and 9, Poupon et al. teaches the composition of the invention comprising a source of amino acids lacking in methionine, with the missing methionine being replaced with homocysteine (Col. 3, lines 8 – 10). Homocysteine is added as a replacement for the methionine, that is that the homocysteine content corresponds, in molar equivalents, to the lack of methionine (Col. 2, lines 3 – 6). The composition formulated for human contains a methionine content reduced by x %, with x being at least 50 (Col. 11, lines 3 – 4, claim 1). In a similar manner that taught in Example 1, various compositions were prepared for mice or rats, cats, dogs, or man, lacking approximately 75% of the methionine and with no disclosure regarding the amount of glycine (Col. 3, lines 49 – 51). Moreover, Poupon et al. teaches that the composition will generally be an additional treatment associated with other methods of therapy such as chemotherapy or radiotherapy. The treatment can be continued, for example, for 1 to 4 months. In example 1, methionine content is reduced by 75%. This means the same amount of homocysteine will be used to replace the lacking methionine. Based on the calculation, the molar ratio of homocysteine and methionine is 3:1.
However, Poupon et al. do not teach that there is no glycine in the composition.
Amelio et al. disclose that glycine can be directed to the biosynthesis of purines, where it provides two carbon atoms and a nitrogen atom in the purine ring (page 195, Left Col., para. 2). Glycine is also an integral component of glutathione, therefore, the main antioxidant molecule of the cell, this amino acid is also required to maintain the cellular redox balance. In the mitochondria, glycine also fuels heme biosynthesis and thus sustains oxidative phosphorylation. It has been shown that glycine uptake and catabolism is able to promote tumourigenesis and malignancy, suggesting that glycine metabolism could in principle be a target for therapeutic intervention. Studies confirm that glycine deprivation may be a new route for human cancer chemotherapy (page 195, Right Col., para. 1 – 2).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of the amino acid mixture comprising homocysteine and methionine with a 3:1 ratio as taught by Poupon et al. into a composition of amino acid mixture without glycine in view of Amelio et al. because Poupon et al. teach a composition of homocysteine and methionine that is used for cancer treatment and Amelio et al. teach that glycine may fuel cancer cells. One would have been motivated to remove glycine from the composition with the homocysteine to methionine ratio of 3:1 as taught by Poupon et al. in view of Amelio et al. because it is known in the art that glycine would fuel cancer cells, which has the opposite effect compared to the composition taught by Poupon et al.. Therefore, one of the skills in the art would have had a reasonable expectation of success to arrive a supplement comprising an amino acid mixture with the homocysteine to methionine ratio of 3:1 and without glycine because Poupon et al. teach a composition comprising amino acid mixture, such as homocysteine and methionine, for cancer treatment and Amelio et al. teach that glycine would fuel cancer cell, thereby, motivating one of the skill in the art to remove glycine to arrive the claimed invention.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed November 26, 2025, have been fully considered and are found to be not persuasive.
Regarding Hoffman, Applicant argues that there is no evidence in Hoffman that the mixtures are substantially devoid of glycine or they have any ratio of methionine and homocysteine.
Regarding Poupon et al., Applicant argues that there is no evidence in Poupon et al. the mixtures are substantially devoid of glycine. It is important to note that Poupon et al. is cited for the ratio of homocysteine and methionine, not for the absence of glycine and the modified / new rejection is based on Poupon et al. in view of Amelio et al. Amelio et al., as an additional reference, provides the motivation to remove glycine from the glycine. Therefore, the combination of Poupon et al. and Amelio et al. renders the claimed invention obvious.
Conclusion
No claim is found to be allowable.
THIS ACTION IS MADE NON-FINAL.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693