Notice of Pre-AIA or AIA Status
The present application, 18257534, (US 20240043794), filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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 .
Claim(s) 1, 4, 6, 7, 10, 11, 13-17, 19, 20, 21, 48-51, 53, 58 are examined
Priority
The filing receipt, mailed 1/24/2024, states that this application, 18257534, was filed 6/14/2023, and is a 371 of PCT/US2021/063618, filed 12/15/2021 which claims benefit of 63/125,619, filed 12/15/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/25/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Interpretation
The instant specification provides the following definition for peptide:
[0055] The terms "polypeptide," "peptide" and "protein" are used interchangeably herein to refer to a polymer of amino acid residues, wherein the polymer may optionally be conjugated to a moiety that does not consist of amino acids. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non- naturally occurring amino acid polymers.
Therefore, the claim term “peptide” is considered to encompass enzymes and protein macromolecules.
Then instant Specification does not appear to provide a limiting definition of the claim term chelating activity.”
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.
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.
1. Claims 1, 4, 6, 7, 10, 11, 13-17, 19, 20, 21, 48-51, 53, 58 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. This rejection is for lack of written description over the original claims.
The breadth of the claims encompasses any peptide as a part within a protein or enzyme and that comprises superoxide dismutase activity and Cu+, Zn+ chelating activity, wherein the peptide comprises at least 4 amino acid residues, especially when as found interna part of a protein or enzyme, is not actually possessed or described.
MPEP 2163, II, 3. (a) ii) considers that the written description requirement for a claimed gene may be satisfied through sufficient description of a representation number of species by actual reduction to practice, reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics sufficient to show the inventor was in possession of the claimed genus. The MPEP further states that “when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.” The MPEP cautions that for inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus and, instead, that the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation."
The claims are drawn to a peptide comprising superoxide dismutase activity and Cu+, Zn+ chelating activity, wherein the peptide comprises at least 4 amino acid residues, and a superoxide scavenger.
The prior art publication of Boka, 2004, Journal of Inorganic Biochemistry, vol 98, 113 to 122, states:
Copper(II) and zinc(II) complexes of the non-protected forms of the peptides HisValHis and HisValGlyAsp were thoroughly studied in or laboratories and the results have been published recently {12,13].However it should be considered that these peptide sequences comprise an internal part of the native protein molecule and the free amino and carboxylate functions are not available for metal binding in the native enzyme. As a consequence, the clarification of the complex formation processes of the N- and C-terminally protected peptides provides a better approach for the characterisation of the active centre of the enzyme.
In this paper we report the synthesis of Ac-HisValHis-NH2 and Ac-HisValGlyAsp-NH2 and the results of combined potentiometric and spectroscopic studies for copper(II) and zinc(II) complexes of these peptide molecules.
Boka at p. 114, left column, first and paragraphs, (emphasis added).
Thus Boka indicates that it is unpredictable that peptide parts within a native protein will act as chelators when synthesized separately. Boka reports chelator properties using potentiometric and spectroscopic studies of particular and specific peptide complex, as a separate case study.
The Specification does not provide support for the complete range of any tetramer having the claimed properties of superoxide dismutase activity and chelate Cu+ and Zn+. The Specification does not present the structural molecular requirements for such tetramer peptides.
Therefore, it is unpredictable that scope of these generic claims including residues of four within a protein or enzyme, and that have superoxide dismutase activity and chelate Cu+ and Zn+, are possessed by the applicant.
2. Claim 10 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 10, in line 2, recites the term “tertramethyl”, which renders the claim vague and indefinite, because the term does not seem to be found in the art.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 4, is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Boka, 2004, Journal of Inorganic Biochemistry, vol 98, 113 to 122.
Boka, throughout the publication and abstract, teaches Boka, at pp. 113-114, bridging paragraph, Scheme 1, teach peptides, including tetrapeptide HisValGlyAsp, with chelating activity chelate Cu(II) and Zinc(II) Boka at p. 117-119, para 3.3, teach the tetrapeptide as forming macrochelates for Cu(II) and, at p. 119, Zinc(II). This tetrapeptide contains Aspartate, which is negatively charged and Histidine, which is positively charged, as in claim 4. Boka at p. 117-121, para 3.5, teach the tetrapeptide systems as exhibiting catalytic activity toward the dismutation of superoxide anions. Boka, at p. 114, left column, 2.3, teaches peptide in Tris-HCl buffer, which reads on a supplement that can be used in a cell culture supplement.
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:
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.
1. Claim(s) 1, 6, 7, 14, 15, 16, 17, 48, 49-51, 53, 58 is/are rejected under 35 U.S.C. 103 as being unpatentable over Boka, 2004, Journal of Inorganic Biochemistry, vol 98, 113 to 122 as applied to claims 1, 4, above, and further in view of Ma, US 20190100725, Bar-Or, US 20030130185, and Decker, 1995, Biochemical Pharmacology, Vol 50, number 7, pages 1063 to 1070.
The prior art reference of Boka is relied upon, as above.
Boka does not teach or suggest particular peptide sequences, such as DAHK (SEQ ID NO: 1); peptide concentration; vitamin E or an analog in the cell culture medium or supplement and comprising a 6-chromanol group moiety, methods for growing cells, recovering cells from oxidative stress, and kits.
Ma, US 20190100725, throughout the publication and abstract, teaches substantially albumin-free, chemically defined medium for supporting stem cell growth and differentiation to provide cardiomyocytes, for cardiac injury repair, and at para [0055], teaches superoxide dismutase containing cell culture media, as in instant claims 49, 50.
Ma, at para [0317], teaches:
[0317] To develop an albumin-free and chemically defined medium for cardiac differentiation, hESC line H7 was cultured in E8 medium for cell expansion.sup.10, and induced for cardiac differentiation with Wnt-related small molecules in the chemically defined RPMI 1640 medium, to evaluate the necessity of B27 components (FIG. 1a).sup.2. B27 has 20 components, among which there are four components (bovine serum albumin, catalase, superoxide dismutase and D-galactose) that originate from animals. Similarly to a previous report.sup.11, removing albumin and catalase, superoxide dismutase and progesterone from B27 resulted in very low cardiac differentiation efficacy with cell growth arrest and moderate cell death. To prevent cell growth arrest and improve cardiac differentiation efficiency, 50 μg/mL recombinant human truncated vitronectin (VTN-NC) which could accelerate epithelial-mesenchymal transition (EMT) was added to the medium for the first three days of differentiation.sup.12. However, when preparing the medium, DL-α-tocopherol acetate and DL-α-tocopherol, two vitamin E analogs, were insoluble in the medium without albumin. Hence, whether the water-soluble vitamin E analog, trolox, could support cardiac differentiation with B27 supplement without the first removed four ingredients, and DL-α-tocopherol acetate and DL-α-tocopherol, was tested. . . .
Ma at para [0317], emphasis added.
Ma at reference claim 1, claims an albumin-free cell culture medium supplement, as in instant claim 1; at reference claim 2, claim the medium comprising superoxide dismutase, vitamin E, as in instant claim 14; at reference claim 60, claims a kit, as in instant claim 58; at reference claim 123, claims a method for treating a disease using the invention, as in instant claims
Ma, at para [0089], teach the level of the polypeptide can range from 0.04 milligrams (40 micrograms per Liter); teaches about 5 mg/L, as in claim 7.to about 500
Bar-Or, US 20030130185, throughout the publication and abstract, and at [0013], teaches peptides, as in claim 1; at para [0044]-[0048] teaches Asp Ala His Lys (reference SEQ ID NO:1]; at [0076]-[0077], teaches peptide sequence that can bind Cu(I); at [0153]. Bar Ora, at para [0188], teach that the metal binding compounds of the invention can be used to reduce damage done by Reactive Oxygen Species, describing recovering cells from oxidative stress, as in instant claims 51, 53. Bar-Or at para [0200]-[0204], describe production of a tetrapeptide of reference SEQ ID NO: 1, that is prepared in Dimethylformamide, and partially dried, reading on the supplement of claim 1, reading on instant claim 58.
Decker, throughout the publication and abstract, teaches the 6-chromanol-containing antioxidant U78517F, appears to act as a direct oxygen radical scavenger in cell culture systems containing.
It would have been prima facie obvious before the filing date of the instant application for one of ordinary skill in the art to have combined suggest particular peptide sequences, such as DAHK (SEQ ID NO: 1); peptide concentration; vitamin E or an analog in the cell culture medium or supplement and comprising a 6-chromanol group moiety, methods for growing cells, recovering cells from oxidative stress, and kits, as taught by Ma, and Decker and Bar-Or, with the chelating peptides, including superoxide dismutase, as taught by Boka.
One of ordinary skill in the art would have motivated to have combined particular peptide sequences, such as DAHK (SEQ ID NO: 1); peptide concentration; vitamin E or an analog in the cell culture medium or supplement and comprising a 6-chromanol group moiety, methods for growing cells, recovering cells from oxidative stress, and kits, as taught by Ma, and Decker and Bar-Or, with the chelating peptides, including superoxide dismutase, as taught by Boka.
One of ordinary skill in the art would have motivated to have combined particular peptide sequences, such as DAHK (SEQ ID NO: 1); peptide concentration; vitamin E or an analog in the cell culture medium or supplement and comprising a 6-chromanol group moiety, methods for growing cells, recovering cells from oxidative stress, and kits, as taught by Ma, and Decker and Bar-Or, with the chelating peptides, because Ma, and Decker and Bar-Or provide cell culture media protocols, molecules and tools for reducing the molecular, cellular and tissue damage done by reactive oxygen species (ROS).
2. Claim(s) 10, 11, 13, 14, 15, 19, 20, 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Boka, 2004, Journal of Inorganic Biochemistry, vol 98, 113 to 122, Ma, US 20190100725, Bar-Or, US 20030130185, and Decker, 1995, Biochemical Pharmacology, Vol 50, number 7, pages 1063 to 1070, as applied to claims 1, 4, above, and further in view of Ni, 2016, Free Radical Biology and Medicine vol 90, pages 12 to 23, Ebegboni, 2019, vol 272, pages 117-125, Liu, 2010, Journal of Ocular Pharmacology and Therapeutics, Vol 26, Number 3, pages 249 to 257, and Benaroudj, 2001, Journal of Biological Chemistry, Vol 276, number 26, pages 24261 to 24267.
The prior art references of Boka, 2004, Journal of Inorganic Biochemistry, vol 98, 113 to 122, Ma, US 20190100725, and Bar-Or, US 20030130185 are relied upon as above.
The prior art references of Boka, 2004, Journal of Inorganic Biochemistry, vol 98, 113 to 122, Ma, US 20190100725, and Bar-Or, US 20030130185 do not teach or fairly suggest cell culture medium or supplement comprising a flavonoid; a superoxide scavenger that comprises TEMPO, or variant thereof; that comprises Mito-TEMPO; a vitamin E analog that comprises a 6-chromamol group moiety.
Ni, 2016, Free Radical Biology and Medicine vol 90, pages 12 to 23, teaches throughout the publication and abstract, the mitochondria-targeted antioxidant mito-TEMP in cell culture, (as in claim 13), of cardiomyocytes. Ni, at p. 13, left column, last paragraph, concludes that therapeutic inhibition of mitochondrial reactive oxygen species (ROS) by mito-TEMPO prevented oxidative stress.
Liu, throughout the publication and abstract, teach mannitol as antioxidant by up-regulating the level of catalase in cells.
Ebegboni, throughout the publication and abstract, teaches flavonoids are associated with ROS modulation, reducing the generation of superoxide/hydrogen peroxide, and at p. 118, 2.2, p. 123, 3.4, teaches flavonoids added to cell culture medium, act as antioxidants by scavenge oxygen free radical in vitro cell culture. flavonoids, as in claims 19, 20
Benaroudj, throughout the publication and abstract, teaches trehalose in protecting cells against oxygen radicals, presumably by acting as a free radical scavenger.
One of ordinary skill in the art would have motivated to have combined cell culture medium or supplement comprising a flavonoid; a superoxide scavenger that comprises TEMPO, or variant thereof; that comprises Mito-TEMPO; a vitamin E analog that comprises a 6-chromamol group moiety, as taught by Ni, Ebegboni, Liu, and Benaroudj, with the chelating peptides, including superoxide dismutase, and cell culture methods for reducing ROS as taught by Boka, Ma, and Decker and Bar-Or.
One of ordinary skill in the art would have motivated to have combined cell culture medium or supplement comprising a flavonoid; a superoxide scavenger that comprises TEMPO, or variant thereof; that comprises Mito-TEMPO; a vitamin E analog that comprises a 6-chromamol group moiety, as taught by Ni, Ebegboni, Liu, and Benaroudj, with the chelating peptides, including superoxide dismutase, and cell culture methods for reducing ROS as taught by Boka, Ma, and Decker and Bar-Or, in order to provide cell culture media protocols, molecules and tools for reducing the molecular, cellular and tissue damage done by reactive oxygen species (ROS) and stabilizing cell culture.
Conclusion
Claim(s) 1, 4, 6, 7, 10, 11, 13-17, 19, 20, 21, 48-51, 53, 58 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mark L Shibuya whose telephone number is (571)272-0806. The examiner can normally be reached M-F, 9AM-4:30PM.
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MARK L. SHIBUYA
Primary Patent Examiner
Art Unit 1631
/MARK L SHIBUYA/ Primary Patent Examiner, Art Unit 1631