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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 08/23/2023, 10/23/2024, 01/21/2025, and 01/06/2026 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 15 and 19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “functional health food” in claims 15 and 19 is a relative term which renders the claim indefinite. The term “functional health food” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Given the discussion of the term “functional health food” as a pill, a tablet, a capsule, a powder preparation, a granule, a candy, a syrup, and a drink but not limited thereto, it is not clear what the metes and bounds of the term “functional health food” are. In other words, it is not clear from the claims, specification, or common understanding in the field what features of a composition would render it a “functional health food.” As such, the terms is relative and renders the claim indefinite.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 7 and 11-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 7 and 11-20 are drawn to methods of removing a nitro group from a protein and ameliorating diseases using peptides with a terminal tyrosine. With regard to the peptides, the claim language is broad and includes any peptide of any length and sequence that comprises a tyrosine residue at either terminus. Applicant has, however, only disclosed the following peptides: tyrosine-glutamine (YQ), glutamine-tyrosine (QY), tyrosine-tryptophan (YW), tryptophan-tyrosine (WY), tyrosine-threonine (YT), threonine-tyrosine (TY), tyrosine-arginine (YR), arginine-tyrosine (RY), tyrosine-valine (YV), valine-tyrosine (VY), tyrosine-tyrosine-glutamine (YYQ), glutamine-tyrosine-tyrosine (QYY), tyrosine-threonine-glutamine (YTQ), glutamine-threonine-tyrosine (QTY), tyrosine-tryptophan-glutamine (YWQ), glutamine-tryptophan-tyrosine (QWY), tyrosine-glutamine-glutamine (YQQ), glutamine-glutamine-tyrosine (QQY), tyrosine-tyrosine-tyrosine-glutamine (YYYQ), glutamine-tyrosine-tyrosine-tyrosine (QYYY), tyrosine-tryptophan-threonine-glutamine (YWTQ), glutamine-tryptophan-threonine-tyrosine (QWTY), tyrosine-8 random amino acids-tyrosine (Y(A)8Y), tyrosine-18 random amino acids-tyrosine (Y(A)18Y), or tyrosine-28 random amino acids-tyrosine (Y(A)28Y). These peptides only cover a very small sample of potential embodiments claimed by the claim language, as, excluding the peptides with “random” amino acids, there are only 22 embodiments and none surpass four amino acids in length. Further, they incorporate just six different amino acids, whereas the claim language includes any standard, unnatural, or uncommon amino acid. Given that the vast majority of amino acids are not incorporated and the disclosed embodiments are all similar lengths, this clearly is not a representative sample of the potential peptides claimed. Here, a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. With regard to the peptides with “random” amino acids, Applicant has not disclosed any embodiments of the peptides, and it is not clear that the claimed peptides would serve their desired function given that different structures impart very different functions. Moreover, only considering the standard 20 amino acids, the tyrosine-28 random amino acids-tyrosine (Y(A)28Y) has 2028 different potential embodiments, of which Applicant has not disclosed any desired, functional, or clearly owned/possessed embodiments. Given the different sequences that these embodiments can have, which would have very different structures and functions, it would not be obvious to one having ordinary skill in the art which embodiments achieve the desired function. As such, it would not be clear to one having ordinary skill in the art that Applicant was in possession of the entire scope of the claimed embodiments at the time of filing. It is advised that Applicant amend the scope of the claimed embodiments to the 22 short peptides for which the specification fulfills the written description requirement.
Claims 7 and 11-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for making and using tyrosine-glutamine (YQ), glutamine-tyrosine (QY), tyrosine-tryptophan (YW), tryptophan-tyrosine (WY), tyrosine-threonine (YT), threonine-tyrosine (TY), tyrosine-arginine (YR), arginine-tyrosine (RY), tyrosine-valine (YV), valine-tyrosine (VY), tyrosine-tyrosine-glutamine (YYQ), glutamine-tyrosine-tyrosine (QYY), tyrosine-threonine-glutamine (YTQ), glutamine-threonine-tyrosine (QTY), tyrosine-tryptophan-glutamine (YWQ), glutamine-tryptophan-tyrosine (QWY), tyrosine-glutamine-glutamine (YQQ), glutamine-glutamine-tyrosine (QQY), tyrosine-tyrosine-tyrosine-glutamine (YYYQ), glutamine-tyrosine-tyrosine-tyrosine (QYYY), tyrosine-tryptophan-threonine-glutamine (YWTQ), glutamine-tryptophan-threonine-tyrosine (QWTY), does not reasonably provide enablement for tyrosine-8 random amino acids-tyrosine (Y(A)8Y), tyrosine-18 random amino acids-tyrosine (Y(A)18Y), tyrosine-28 random amino acids-tyrosine (Y(A)28Y), or other embodiments of the peptide comprising a terminal tyrosine. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in the case In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. See Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
With regard to the breadth of the claims and the nature of the invention, as discussed above, claims 7 and 11-20 are drawn to methods of removing a nitro group from a protein and ameliorating diseases using peptides with a terminal tyrosine. The nature of the invention is therefore related to peptides and methods of using a peptide of any size or length comprising a terminal tyrosine residue. By nature, peptides with different primary sequences have vastly different structures and functions. As such, the nature of the invention is such that, in order to ensure proper function of the invention, a person having ordinary skill in the art would have to know which sequences or key portions of sequences is necessarily to confer the function. Similarly, a person having ordinary skill would have to know which amino acids or amino acid sequences distort the structure and function of the peptide. In short, they would need a representative sample of peptides to cover the scope of the claims. Applicant has not, however, provided substantial or representative samples for peptides longer than four amino acids long or those containing amino acids outside of Y, W, Q, R, T, and V.
With regard to the existence of working examples, amount of direction provided by Applicant, and the quantity of experimentation needed to make or use the invention based on the content of the disclosure, Applicant has, only disclosed the following peptides: tyrosine-glutamine (YQ), glutamine-tyrosine (QY), tyrosine-tryptophan (YW), tryptophan-tyrosine (WY), tyrosine-threonine (YT), threonine-tyrosine (TY), tyrosine-arginine (YR), arginine-tyrosine (RY), tyrosine-valine (YV), valine-tyrosine (VY), tyrosine-tyrosine-glutamine (YYQ), glutamine-tyrosine-tyrosine (QYY), tyrosine-threonine-glutamine (YTQ), glutamine-threonine-tyrosine (QTY), tyrosine-tryptophan-glutamine (YWQ), glutamine-tryptophan-tyrosine (QWY), tyrosine-glutamine-glutamine (YQQ), glutamine-glutamine-tyrosine (QQY), tyrosine-tyrosine-tyrosine-glutamine (YYYQ), glutamine-tyrosine-tyrosine-tyrosine (QYYY), tyrosine-tryptophan-threonine-glutamine (YWTQ), glutamine-tryptophan-threonine-tyrosine (QWTY), tyrosine-8 random amino acids-tyrosine (Y(A)8Y), tyrosine-18 random amino acids-tyrosine (Y(A)18Y), or tyrosine-28 random amino acids-tyrosine (Y(A)28Y). As discussed above, these peptides only cover a very small sample of potential embodiments claimed by the claim language, as, excluding the peptides with “random” amino acids, there are only 22 embodiments and none surpass four amino acids in length. Further, they incorporate just six different amino acids, whereas the claim language includes any standard amino acid (~20 natural amino acids), as well as any unnatural or uncommon amino acid. With regard to the peptides with “random” amino acids, Applicant has not disclosed any embodiments of the peptides, and it is not clear that the claimed peptides would serve their desired function given that different structures impart very different functions. Moreover, as discussed above and with regard to the level of predictability in the art and the state of the art, only considering the standard 20 amino acids, the tyrosine-28 random amino acids-tyrosine (Y(A)28Y) has 2028 different potential embodiments, of which Applicant has not disclosed any desired, functional, or clearly owned/possessed embodiments. Given the widely different sequences that these embodiments can have, which would have very different structures and functions, it would not be obvious to one having ordinary skill in the art which embodiments achieve the desired function. As such, it would not be clear to one having ordinary skill in the art which peptides achieve the desired function of the claimed methods. Here, it would not be clear to one having ordinary skill in the art how to make or use the entire scope of the invention, as the working examples only cover a narrow sample of the claimed peptides, and it is clear that not every claimed sequence would serve the desired function. It is advised that Applicant amend the claims to the 22 short peptides discussed above for which the specification enables a person having ordinary skill in the art to make and use the invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 7 and 11-14 and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Ano et al. (as noted on the IDS filed 10/23/2024, Ano, Yasuhisa et al. “Tryptophan-Tyrosine Dipeptide, the Core Sequence of β-Lactolin, Improves Memory by Modulating the Dopamine System.” Nutrients vol. 11,2 348. 6 Feb. 2019).
With regard to claim 7, Ano et al. teach the use of short peptides comprising a terminal tyrosine residue, including WY and YW, to improve or restore memory impairments (see Abstract). They argue that the peptides may be beneficial in preventing or treating age-related cognitive like Alzheimer’s disease (see page 8, paragraph 2). Although Ano et al. did not explicitly apply the peptides to treat Alzheimer’s disease, they provide a clear motivation by arguing that the aforementioned short peptides function in the same way as MAO-B inhibitors, which are promising Alzheimer’s disease drugs (see page 8, paragraph 2). Both the short peptides and MAO-B inhibitors function by increasing dopamine in the brain and preventing or treating age-related cognitive decline (see page 8, paragraph 2). As such, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to try to use short peptides with terminal tyrosine residues, specifically WY and YW, to treat Alzheimer’s disease.). The instant application further asserts that Alzheimer’s disease is an example of a disease “caused by protein nitration” (see [0048]). Here, the prior art teaches and motivates a method of treating a disease caused by protein nitration, Alzheimer’s disease, by administering short peptides with terminal tyrosine residues. In this case, "the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer" Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. As applied to this case, if the short peptides comprising a terminal tyrosine residue function as claimed in the instant application when applied to diseases caused by nitration like Alzheimer’s disease, then their use in Ano et al. would have performed said function independent of their knowledge of its mechanism. In other words, despite the unclear mechanism of action, Ano et al. teach a method of removing a nitro group from nitrotyrosine included in a protein by treating the protein comprising the nitrotyrosine with a short peptide with a terminal tyrosine residue.
With regard to claim 11, Ano et al. teach a method for improving cognitive function comprising administering to a subject a composition comprising a short peptide with a terminal tyrosine residue. Ano et al. do not explicitly teach this method in treating diseases caused by nitration. As discussed above, Ano et al. do, however, teach an explicit motivation for using this method to treat Alzheimer’s disease, which is caused by nitration, as argued in the specification of the instant application (see [0048]). Ano et al. teach the use of short peptides comprising a terminal tyrosine residue, including WY and YW, to improve or restore memory impairments (see Abstract). They argue that the peptides may be beneficial in preventing or treating age-related cognitive like Alzheimer’s disease (see page 8, paragraph 2). Although Ano et al. did not explicitly apply the peptides to treat Alzheimer’s disease, they provide a clear motivation by arguing that the aforementioned short peptides function in the same way as MAO-B inhibitors, which are promising Alzheimer’s disease drugs (see page 8, paragraph 2). Both the short peptides and MAO-B inhibitors function by increasing dopamine in the brain and preventing or treating age-related cognitive decline (see page 8, paragraph 2). As such, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to try to use short peptides with terminal tyrosine residues, specifically WY and YW, to treat Alzheimer’s disease.
With regard to claim 12, as discussed above, Ano et al. teach and motivate the method discussed above comprising the use of short peptides comprising a terminal tyrosine residue, including WY and YW (see page 2, paragraph 4).
With regard to claim 13, Ano et al. teach and motivate the method discussed above comprising administering to a patient a short peptide comprising a terminal tyrosine to treat cognitive impairment (see Abstract). Ano et al. do not teach that the short peptide removes a nitro group from a protein comprising a nitrotyrosine selected from the proteins recited in claim 13 of the instant application. As discussed above, Ano et al. teach and motivate administering short peptides with terminal tyrosine residues to treat Alzheimer’s disease, which the instant application claims is caused by nitration. Here, given that Ano et al. teach administering the aforementioned peptides, which the instant application asserts function to remove a nitro group from the nitrotyrosine proteins recited in claim 13, the peptides would have functioned to do so independent of whether Ano et al. teach the mechanism. In other words, as recited above, the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. In the instant case, Ano et al. taught the use of the peptides in the relevant context, which would have performed the claimed function independent of their knowledge of the mechanism.
With regard to claim 14, as discussed above, Ano et al. teach a method for improving cognitive function comprising administering to a subject a composition comprising a short peptide with a terminal tyrosine residue. Ano et al. do not explicitly teach this method in treating diseases caused by nitration. As discussed above, Ano et al. do, however, teach an explicit motivation for using this method to treat Alzheimer’s disease, which is caused by nitration, as argued in the specification of the instant application (see [0048]). Ano et al. teach the use of short peptides comprising a terminal tyrosine residue, including WY and YW, to improve or restore memory impairments (see Abstract). They argue that the peptides may be beneficial in preventing or treating age-related cognitive like Alzheimer’s disease (see page 8, paragraph 2). Although Ano et al. did not explicitly apply the peptides to treat Alzheimer’s disease, they provide a clear motivation by arguing that the aforementioned short peptides function in the same way as MAO-B inhibitors, which are promising Alzheimer’s disease drugs (see page 8, paragraph 2). Both the short peptides and MAO-B inhibitors function by increasing dopamine in the brain and preventing or treating age-related cognitive decline (see page 8, paragraph 2). As such, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to try to use short peptides with terminal tyrosine residues, specifically WY and YW, to treat Alzheimer’s disease.
With regard to claim 17, as discussed above, Ano et al. teach a method for improving cognitive function comprising administering to a subject a composition comprising a short peptide with a terminal tyrosine residue. Ano et al. do not explicitly teach this method in treating diseases caused by an increase in reactive oxygen or reactive nitrogen species. As discussed above, Ano et al. do, however, teach an explicit motivation for using this method to treat Alzheimer’s disease, which is caused by reactive oxygen or reactive nitrogen species, as argued in the specification of the instant application (see claim 18). Ano et al. teach the use of short peptides comprising a terminal tyrosine residue, including WY and YW, to improve or restore memory impairments (see Abstract). They argue that the peptides may be beneficial in preventing or treating age-related cognitive like Alzheimer’s disease (see page 8, paragraph 2). As discussed above, although Ano et al. did not explicitly apply the peptides to treat Alzheimer’s disease, they provide a clear motivation by arguing that the aforementioned short peptides function by increasing dopamine in the brain and preventing or treating age-related cognitive decline, which is the same function of MAO-B inhibitors (see page 8, paragraph 2). Given this shared mechanism, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to try to use short peptides with terminal tyrosine residues, specifically WY and YW, to treat Alzheimer’s disease.
With regard to claim 18, as discussed above, Ano et al. teach a method for improving cognitive function comprising administering to a subject a composition comprising a short peptide with a terminal tyrosine residue. Ano et al. do not explicitly teach this method in treating diseases caused by an increase in reactive oxygen or reactive nitrogen species. As discussed above, Ano et al. do, however, teach an explicit motivation for using this method to treat Alzheimer’s disease, which is caused by an increase in reactive oxygen or reactive nitrogen species, as argued in the specification of the instant application (see claim 18). Ano et al. teach the use of short peptides comprising a terminal tyrosine residue, including WY and YW, to improve or restore memory impairments (see Abstract). They argue that the peptides may be beneficial in preventing or treating age-related cognitive like Alzheimer’s disease (see page 8, paragraph 2). Although Ano et al. did not explicitly apply the peptides to treat Alzheimer’s disease, they provide a clear motivation by arguing that the aforementioned short peptides function in the same way as MAO-B inhibitors, by increasing dopamine in the brain and preventing or treating age-related cognitive decline (see page 8, paragraph 2). Given their shared mechanism, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to try to use short peptides with terminal tyrosine residues, specifically WY and YW, to treat Alzheimer’s disease.
Claims 15-16 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Ano et al. (as noted on the IDS filed 10/23/2024, Ano, Yasuhisa et al. “Tryptophan-Tyrosine Dipeptide, the Core Sequence of β-Lactolin, Improves Memory by Modulating the Dopamine System.” Nutrients vol. 11,2 348. 6 Feb. 2019), as applied to claims 11-14 and 17-18 above, and further in view of Sikora et al. (Sikora, Karol et al. “The Role of Counter-Ions in Peptides-An Overview.” Pharmaceuticals (Basel, Switzerland) vol. 13,12 442. 3 Dec. 2020).
With regard to claim 15, Ano et al. teach that effective intake of the WY dipeptide and other similar dipeptides via supplements or nutraceutical foods including certain whey peptide preparations that might be beneficial for improving cognitive function in older age (see page 9 paragraph 3). Ano et al. do not, however, explicitly teach the use of a salt. Sikora et al. teach that using counter-ions to form salts of short peptides can meaningfully affect the stability, solubility, conformation, and pharmacokinetic profile of final formulations, which can all significantly alter its properties as a pharmaceutical or supplement (see page 22, paragraph 1). Given the clear motivations by Ano et al. to use the peptides in a food composition and the motivations by Sikora et al. to use salt forms of similar short peptides, it would have been obvious to one having ordinary skill in the art prior to the effective filing date to combine the references to use a salt form suitable as a food.
With regard to claim 16, Ano et al. teach that MAO-B inhibitors have been used as drugs to induce dopamine levels because it is suggested that some MAO-B inhibitors have a potential as therapeutic or preventive treatment for dementia including Alzheimer’s disease (see page 8, paragraph 2). They also show that the administration of WY dipeptide increased total dopamine levels in the hippocampus and frontal cortex (see page 8, paragraph 2). These results suggest that WY dipeptide increase dopamine levels in the brain by inhibiting MAO-B activity. Those findings suggest that the WY dipeptide exerts its beneficial effect on the prevention of age-related cognitive decline by increasing dopaminergic activity in the brain (see page 8, paragraph 2). Further, given the clear functional connection between WY dipeptide and MAO-B inhibitor activity, as well the history of use of said inhibitors as drugs, Ano et al. provide a clear motivation to try to use WY dipeptide as a drug or pharmaceutical composition. Here, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to try to use WY dipeptide as a drug or pharmaceutical composition. Ano et al. do not, however, explicitly motivate its use as a pharmaceutically acceptable salt. As discussed above, Sikora et al. teach that using counter-ions to form salts of short peptides can meaningfully affect the stability, solubility, conformation, and pharmacokinetic profile of final formulations, which can all significantly alter its properties as a pharmaceutical or supplement (see page 22, paragraph 1). Given the clear motivations by Ano et al. to use the peptides in a drug or pharmaceutical composition and the motivations by Sikora et al. to use salt forms of similar short peptides, it would have been obvious to one having ordinary skill in the art to use a pharmaceutically acceptable salt of the peptide in a drug composition.
With regard to claim 19, Ano et al. teach that effective intake of the WY dipeptide and other similar dipeptides via supplements or nutraceutical foods including certain whey peptide preparations might be beneficial for improving cognitive function in older age (see page 9 paragraph 3). Ano et al. do not, however, explicitly teach the use of a salt. Sikora et al. teach that using counter-ions to form salts of short peptides can meaningfully affect the stability, solubility, conformation, and pharmacokinetic profile of final formulations, which can all significantly alter its properties as a pharmaceutical or supplement (see page 22, paragraph 1). Given the clear motivations by Ano et al. to use the peptides in a food composition and the motivations by Sikora et al. to use salt forms of similar short peptides, it would have been obvious to one having ordinary skill in the art to use a salt form suitable for use in food.
With regard to claim 20, Ano et al. teach that MAO-B inhibitors have been used as drugs to induce dopamine levels because it is suggested that some MAO-B inhibitors have a potential as therapeutic or preventive treatment for dementia including Alzheimer’s disease (see page 8, paragraph 2). They also show that the administration of WY dipeptide increased total dopamine levels in the hippocampus and frontal cortex (see page 8, paragraph 2). These results suggest that WY dipeptide increase dopamine levels in the brain by inhibiting MAO-B activity. Those findings suggest that the WY dipeptide exerts its beneficial effect on the prevention of age-related cognitive decline by increasing dopaminergic activity in the brain (see page 8, paragraph 2). Further, given the clear functional connection between WY dipeptide and MAO-B inhibitor activity, as well the history of use of said inhibitors as drugs, Ano et al. provide a clear motivation to try to use WY dipeptide as a drug or pharmaceutical composition. Here, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to try to use WY dipeptide as a drug or pharmaceutical composition. Ano et al. do not, however, explicitly motivate its use as a pharmaceutically acceptable salt. As discussed above, Sikora et al. teach that using counter-ions to form salts of short peptides can meaningfully affect the stability, solubility, conformation, and pharmacokinetic profile of final formulations, which can all significantly alter its properties as a pharmaceutical or supplement (see page 22, paragraph 1). Given the clear motivations by Ano et al. to use the peptides in a drug or pharmaceutical composition and the motivations by Sikora et al. to use salt forms of similar short peptides, it would have been obvious to one having ordinary skill in the art to use a pharmaceutically acceptable salt of the peptide in a drug composition.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 7 and 11-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9, 10, 12, 14, and 15 of copending Application No. 18/013,412, hereinafter Kim et al., in view of Ano et al. (as noted on the IDS filed 10/23/2024, Ano, Yasuhisa et al. “Tryptophan-Tyrosine Dipeptide, the Core Sequence of β-Lactolin, Improves Memory by Modulating the Dopamine System.” Nutrients vol. 11,2 348. 6 Feb. 2019), as evidenced by Balzano et al. (Balzano, Tiziano et al. Chronic hyperammonemia induces peripheral inflammation that leads to cognitive impairment in rats: Reversed by anti-TNF-α treatment, Journal of Hepatology, vol. 73, no. 3, 2020, 582-592).
With regard to claim 7, Kim et al. claim a method for ameliorating or treating a disease caused by nitration of tyrosine in a protein, the method comprising administering a composition comprising tyrosine or a salt thereof to a subject in need thereof wherein the disease is selected from the group consisting of glaucoma, diabetes, diabetic retinopathy, cancer, acute kidney injury, hyperammonemia, and a combination thereof (see claim 9). Kim et al. do not, however, explicitly claim a method for removing a nitro group from nitrotyrosine included in a protein, the method comprising treating the protein having the nitrotyrosine with a peptide with terminal tyrosine. Here, Kim et al. do not claim the use of a peptide comprising a terminal tyrosine, and they do not teach the mechanism of action recited above. They do, however, teach a method of treating a disease caused by protein nitration by administering to a subject a composition comprising tyrosine or a salt thereof. With regard to the limitation of the peptide comprising a terminal tyrosine, Ano et al. teach that small peptides comprising terminal tryptophan and tyrosine resides like WY led to cognitive benefits like improved memory, particularly spatial memory (see Abstract). Although Ano et al. do not explicitly teach treating hyperammonemia, the disease is commonly known as affecting the brain via inflammation and memory loss, particularly spatial memory impairment (see page 582, paragraph 3). This teaching provides a clear motivation to use a terminal tyrosine in a tyrosine-containing composition for treating the symptoms of diseases like hyperammonemia (see page 582, paragraph 3). As such, given the overlap in symptoms of hyperammonemia and the known benefits of using short peptides with terminal tyrosine residues like WY, it would have been obvious to one having ordinary skill prior to the effective filing date of the instant application to try to use short peptides like WY with terminal tyrosine residues to treat conditions affecting spatial memory loss like hyperammonemia. With regard to the limitation of the mechanism of removing a nitro group from a nitrotyrosine, the specification of the instant application argues that short peptides comprising terminal tyrosine residues, like tyrosine-tryptophan, improve cognitive function experimentally and function to remove nitro groups from nitrotyrosine residues on proteins like glutamine synthetase (see [0030] and figures 6 and 18). The reference application further asserts that hyperammonemia is an example of a disease “caused by protein nitration” (see claim 1). Here, the prior art teaches and motivates a method of treating a disease caused by protein nitration, hyperammonemia, by administering short peptides with terminal tyrosine residues. In this case, "the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer" Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. As applied to this case, if the short peptides comprising a terminal tyrosine residue function as claimed in the instant application when applied to diseases caused by nitration like hyperammonemia, then their use in Ano et al. would have performed said function independent of their knowledge of its mechanism. In other words, despite the unclear mechanism of action, Ano et al. teach a method of removing a nitro group from nitrotyrosine included in a protein by treating the protein comprising the nitrotyrosine with a short peptide with a terminal tyrosine residue.
With regard to claim 11, Kim et al. claim a method for ameliorating or treating a disease caused by nitration of tyrosine in protein, the method comprising administering a composition comprising tyrosine or a salt thereof to a subject in need thereof wherein the disease is selected from the group consisting of glaucoma, diabetes, diabetic retinopathy, cancer, acute kidney injury, hyperammonemia, and a combination thereof. Kim et al. do not, however, explicitly claim the use of a terminal tyrosine residue in the composition comprising tyrosine. As discussed above, Ano et al. teach that small peptides comprising terminal tryptophan and tyrosine resides like WY led to cognitive benefits like improved memory, particularly spatial memory (see Abstract). Although Ano et al. do not explicitly teach treating hyperammonemia, the disease is commonly known as affecting the brain via inflammation and memory loss, particularly spatial memory impairment (see page 582, paragraph 3). This teaching provides a clear motivation to use a terminal tyrosine in a tyrosine-containing composition for treating the symptoms of diseases like hyperammonemia (see page 582, paragraph 3). As such, given the overlap in symptoms and the known benefits of using short peptides with terminal tyrosine residues like WY, it would have been obvious to one having ordinary skill prior to the effective filing date of the instant application to try to use short peptides like WY with terminal tyrosine residues to treat conditions affecting memory loss like hyperammonemia.
With regard to claim 12, Kim et al, claim the method discussed above, but they do not claim the use of a peptide with terminal tyrosine at either terminus or 1-29 amino acids connected to the tyrosine. As discussed above, Ano et al. teach that small peptides comprising terminal tryptophan and tyrosine resides like WY led to cognitive benefits like improved memory, particularly spatial memory (see Abstract). Although Ano et al. do not explicitly teach treating hyperammonemia, the disease is commonly known as affecting the brain via inflammation and memory loss, particularly spatial memory impairment (see page 582, paragraph 3). This teaching provides a clear motivation to use a dipeptide comprising a terminal tyrosine in a tyrosine-containing composition for treating the symptoms of diseases like hyperammonemia (see page 582, paragraph 3). As such, given the overlap in symptoms and the known benefits of using dipeptides with terminal tyrosine residues like WY, it would have been obvious to one having ordinary skill prior to the effective filing date of the instant application to try to use dipeptides like WY with terminal tyrosine residues to treat conditions affecting memory loss like hyperammonemia. Although Ano et al. do not teach the entire claimed range of 1-29 amino acids in length, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. For example, In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990), the prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped. Here, Ano et al. teach the use of single amino acids and dipeptides, which clearly overlaps with the claimed range (see page 5, Figure 2).
With regard to claim 13, Kim et al. claim the method discussed above wherein the nitration of tyrosine in the protein is nitration of tyrosine in any protein selected from the group consisting of glutamine synthetase, insulin receptor ß subunit, Mn superoxide dismutase, Cu/Zn superoxide dismutase, annexin IV, glutamate dehydrogenase, 3-α-OH steroid dehydrogenase, catalase, and more (see claim 10).
With regard to claim 14, Kim et al. claim the method discussed above wherein the disease is caused by protein nitration and the disease is acute kidney injury (see claim 1).
With regard to claim 15, Kim et al. claim the method discussed above wherein the composition is included in a functional health food (see claim 14), and the tyrosine can be in salt form (see claim 1).
With regard to claim 16, Kim et al. claim the method discussed above wherein the composition a pharmaceutical composition (see claim 15), and the tyrosine can be in salt form (see claim 1).
With regard to claim 17, Kim et al. claim a method for ameliorating or treating a disease caused by nitration of tyrosine in a protein, the method comprising administering a composition comprising tyrosine or a salt thereof to a subject in need thereof wherein the disease is selected from the group consisting of glaucoma, diabetes, diabetic retinopathy, cancer, acute kidney injury, hyperammonemia, and a combination thereof (see claim 9). Kim et al. do not explicitly claim a method for ameliorating a disease caused by in an increase in reactive oxygen species/reactive nitrogen species, the method comprising administering to a subject in need thereof a composition comprising a peptide with terminal tyrosine or a salt thereof. As discussed above, Ano et al. provide a clear motivation for using a terminal tyrosine given cognitive improvements when administered to a subject. Given this, it would have been obvious to one having ordinary skill in the art to use a peptide comprising a terminal tyrosine in treating diseases like hyperammonemia, particularly given its effects in improving spatial memory (see Abstract). Further, Kim et al. claim a method of treating hyperammonemia, which the instant application defines as a disease caused by an increase in reactive oxygen species/reactive nitrogen species (see claims 17 and 18). As such, Kim et al. do teach a method of ameliorating or treating a disease caused by an increase in reactive oxygen/nitrogen species because hyperammonemia is described as being caused by said increase in the instant application.
With regard to claim 18, Kim et al. claim the method discussed above wherein the disease is caused by protein nitration and the disease is acute kidney injury (see claim 1).
With regard to claim 19, Kim et al. claim the method discussed above wherein the composition is included in a functional health food (see claim 14), and the tyrosine can be in salt form (see claim 1).
With regard to claim 20, Kim et al. claim the method discussed above wherein the composition a pharmaceutical composition (see claim 15), and the tyrosine can be in salt form (see claim 1).
This is a provisional nonstatutory double patenting rejection.
Summary
Claims 7 and 11-20 are rejected under 35 U.S.C. 112a for failing to fulfill the requirements of written description and scope of enablement. Claims 7 and 11-20 are rejected on the grounds of obviousness under 35 U.S.C. 103. Claims 7 and 11-20 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable.
Conclusion
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/BRENDAN P. OLISS/Examiner, Art Unit 1658
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654