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 . 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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9 Sept, 2025 has been entered.
Claims Status
Claims 1-3 and 5-21 are pending.
Claims 1, 8, and 14 have been amended.
Claims 20 and 21 are new.
Withdrawn Rejections
The rejection of claims 8-13 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite due to uncertainty as to what constitutes a derivative is hereby withdrawn due to amendment.
The rejection of claim(s) 8, 9, 13-15, and 19 under 35 U.S.C. 102(a)(1) as being anticipated by Gushchina et al (Mol. Ther. (2017) 25(10) p2360-2371) is hereby withdrawn due to amendment.
The rejection of claim(s) 8, 9, and 13 under 35 U.S.C. 102(a)(1) as being anticipated by Schuler et al (PNAS (2010) 107(1) p419-423) is hereby withdrawn due to amendment.
The rejection of claim(s) 8-19 under 35 U.S.C. 103 as being unpatentable over Gushchina et al (Mol. Ther. (2017) 25(10) p2360-2371) in view of Sitzia et al (Front. Neurol. (23 July, 2019) 10 article 756) and Le Tourneau et al (J. Natl. Cancer Inst. (2009) 101 p708-720) is hereby withdrawn due to amendment.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 112(a)
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 1-3 and 5-20 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.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient" (MPEP 2163).
A claimed genus may be satisfied through sufficient description of a representative number of species or disclosure of relevant, identifying characteristics such as functional characteristics coupled with a known or disclosed correlation between function and structure(MPEP 2163(3)a(II)). The number of species that describe the genus must be adequate to describe the entire genus; if there is substantial variability, a large number of species must be described.
The analysis for adequate written description considers (a) actual reduction to practice, (b) disclosure of drawings or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure and (d) representative number of samples.
The issue at question is what constitutes MG53 with activity that will be useful in the claimed methods.
(a and b) actual reduction to practice and disclosure of drawings or structural chemical formulas: The claims limit the therapeutic to MG53, or variants with 1-3 amino acid substitutions compared to the native sequence.
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure: With respect to the term MG53, applicants are claiming a method using MG53 with up to three mutations. This means that the mutant or derivative must have the functional ability to improve the function of the tissue. However, applicants have not taught what structure is required for activity. A person of skill in the art would not understand what sequence/hydrophobicity/charge features are required to meet this functional requirement. In essence, applicants have defined a crucial part of their invention by function. That is not sufficient to meet the written description requirement.
Applicants have stated that mutants of MG53 are known in the art, and reference Xiao et al (US 20150361146) and other documents from the same patent family. However, that reference merely discusses mutating 7 Cys residues (abstract), which does not teach which residues in this 477 AA protein (in the human homolog) are required for activity.
Nor is it clear that anyone has determined what portions of the polypeptide are required for activity. The UniProt variant viewer for human TRI72 (downloaded 27 Aug, 2024)(which is the same as MG53, note paragraph 4 of the specification) lists 630 known variants of the protein, throughout the sequence, the significance of each is either believed to be detrimental, or is unknown.
It is also apparent that a person of skill in the art will be unable to determine a priori which mutants will retain activity without some knowledge of what part of the polypeptide is important. Guo et al (PNAS (2004) 101(25) p9205-9210) discuss random mutations of a DNA repair enzyme, which inactivate the protein about a third of the time (abstract). Note that this is comparable to other studies using other proteins (abstract). Yampolsky et al (Genetics (2005) 170 p1459-1472), using a different methodology, found that even conservative substitutions are likely to be problematic (table 3, p1465, top of page). It is also not possible to use computer docking to predict how variants will bind. Lowe (Blog “In the Pipeline” entry of 7 Sept, 2022) discusses an experiment where experimental results were compared to computer predictions. A library of 39K compounds was screened against E. coli for growth inhibition, finding 218 actives (including known antibiotics) (1st page, 3d paragraph). These 218 compounds were computer docked against 296 essential bacterial proteins using multiple docking protocols (1st page, 3d paragraph) along with 100 randomly selected inactive compounds from the screen (2nd page, 1st paragraph). The computer docking did poorly in replicating the experimental data, with the number of predicted strong binding interactions essentially the same between the known binders and the known inactive (2nd page, 2nd paragraph). In addition, of the 142 previously known compound/target interactions, the computer found 3 (2nd page, 2nd paragraph). In other words, several years after applicant’s priority date, it was impossible to use a computer to predict which variants will bind.
(d) representative number of samples: Applicants used human MG53 for all experiments where a drug was administered, and the prior art gives a few additional variants, all mutated at one of 7 positions. Given as the universe of compounds that can be used in the claims is limited only by the imagination of the chemist making it, and that it is not possible to extrapolate from these examples, this is not sufficient to meet the written description requirement.
response to applicant’s arguments
Applicants argue written description does not require examples or reduction to practice, that MG53 is highly conserved between species, that the domain believed responsible for interactions with partners has been structurally characterized, that Cys242 is critical for oligomer formation, and that the 630 mutations described in the UniProt variant viewer wound not reasonably be expected to cause a loss of activity because the only known mutant that causes a loss of activity is at position 242.
Applicant's arguments filed 9 Sept, 2025 have been fully considered but they are not persuasive.
Applicants argue that written description does not require examples or reduction to practice. While true, it is not clear how this overcomes the rejection, as it is not known what parts of the sequence are tolerant to mutations. A clear case has been made that a person of skill in the art would not know which amino acids, beyond the Cys residues, can or cannot be modified without impacting activity.
Applicants argue that the protein is highly conserved between species. However, this does not make it clear what portions can be modified. The UniProt viewer lists numerous activities of the protein, including ubiquination and binding to phospholipids, and some of which are speculative. It is not clear which of these are responsible for the activity required by applicant’s claimed method. In other words, a mutant may damage a feature of the protein in its normal use that is not necessary for applicant’s method.
Applicants argue that a structure of the important section of the protein is known. However, that does not tell us how the protein interacts with whatever species through which it mediates the effects required for applicant’s method. Applicants argue that it is known that Cys242 is critical, and that other locations would be understood to be not susceptible to mutation. However, just because one site near the middle of the primary sequence is known to be important for some activities does not mean it is the only important residue for activity. The UniProt variant viewer lists hundreds of known variants, some of which are likely pathogenic, most of which have a predicted consequence, and many of which are of uncertain significance.
Claim Rejections - 35 USC § 102
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) 1-3, 5, 8, 9, 13, and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jia et al (Nat. Commun. (2014) 5:4387).
Jia et al discuss treatment of acute lung injury with MG53 (title). Mouse models of this repetitively treated with rhMG53 improved lung structure (abstract). A model used a 4 week disease course with treatment (7th page, 2nd column, 4th paragraph).
Acute lung injury is not a disorder of muscle, so the muscle tissue of these patients was non-diseased and not acutely injured, so will inherently improve the muscle performance. Thus, the reference anticipates claims 1, 3, 8, and 21
This is the same material, so it will necessarily have the same effect, anticipating claims 2 and 13.
The experiment was run for 4 weeks, anticipating claims 5 and 9.
response to applicant’s arguments
Applicants argue that Jia does not mention improvement of muscle performance
Applicant's arguments filed 9 Sept, 2025 have been fully considered but they are not persuasive.
This is the same therapeutic administered to a patient with healthy muscle tissue. As noted in the rejection, it will inherently improve muscle performance.
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.
Claim(s) 1-3, 5-13, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Jia et al (Nat. Commun. (2014) 5:4387) in view of Chow et al (Am. J. Respir. Cell Mol.Biol. (2003) 29 p427-431) and Le Tourneau et al (J. Natl. Cancer Inst. (2009) 101 p708-720).
The teachings of Jia et al were given above, and will not be repeated here. Please note that this reference anticipates claims 1-3, 5, 8, 9, 13, and 21.
The difference between this reference and the remaining claims is that this reference does not discuss a second therapeutic.
Chow et al discusses oxidative stress in the context of acute lung injury; the same disorder discussed by Jia et al. It is clear that oxidative stress is, at least partially, responsible for the lung damage in this disorder (p427, 2nd column, 2nd paragraph). Vitamin E, a naturally occurring antioxidant, was demonstrated to be beneficial in a model of this disorder (p429, 2nd column, 4th and 5th paragraphs). This reference discusses antioxidant treatment of the disorder of Jia et al.
Le Tourneau et al discusses phase 1 clinical trials (title). The main goal of these studies is to establish the dose and dose schedule for new drugs or drug combinations (abstract). The goal is to maximize the efficacy while minimizing side effects (p708, 1st column, 2nd paragraph). A number of different methods to determine these parameters are given (fig 2, p711, top of page). This reference discusses optimizing the dose and dose schedule of drugs and drug combinations.
Therefore, it would be obvious to add the vitamin E of Chow et al to the therapy of Jia et al, to reduce the inflammation of the disorder as described by Chow et al. As this is for the same disorder, an artisan in this field would attempt this therapy with a reasonable expectation of success.
Furthermore, it would be obvious to optimize the dose and dose schedule of the therapeutics to maximize therapeutic effect while minimizing side effects. As this process must be done for every drug and drug combination, an artisan in this field will be experienced enough to have a reasonable expectation of success in this optimization.
Chow et al renders obvious adding an antioxidant to the therapeutic procedure of Jia et al, rendering obvious claims 6, 10, and 11.
Le Tourneau et al renders obvious optimizing the dose and dose schedule, rendering obvious claims 7 and 12.
response to applicant’s arguments
Applicants have repeated the arguments with respect to the rejection under 35 USC 102, above, which were answered there.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
first rejection
Claims 1-3, 5, 8, 9, 13, 14, and 19-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 61, and 63 of copending Application No. 16/598,833 (US 20200179482) (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the competing claims anticipate the instant claims.
Competing claim 1 describes a method of treating a corneal injury, comprising administering to the cornea MG53. Competing claim 61 allows for acute or chronic administration, while competing claim 63 allows for up to semiannually, or longer dosing periods. Note that this will dose several eye tissues which will not be physically damaged, so will inherently improve their performance. Furthermore, at some time, the subject will blink or otherwise do some sort of exercise.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
response to applicant’s arguments
Applicants request that this rejection be held in abeyance until the claims are otherwise allowable. However, until the rejection is overcome, it will remain valid.
second rejection
Claims 1-3, 5, 8, 9, 13, 14, and 19-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/740,547 (US 20220273763) (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the competing claims anticipate the instant claims.
Competing claim 1 describes a method of treating IBD, a chronic disorder, comprising administering MG53. Note that this will dose several tissues which will not be physically damaged, so will inherently improve their performance. Furthermore, at some time, the subject will do some sort of exercise.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
response to applicant’s arguments
Applicants request that this rejection be held in abeyance until the claims are otherwise allowable. However, until the rejection is overcome, it will remain valid.
third rejection
Claims 1-3, 5, 8, 9, 13, 14, and 19-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 13 of copending Application No. 17/549,105 (US 20220150152) (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the competing claims anticipate the instant claims.
Competing claim 1 describes a method of treating a liver injury, comprising administering MG53. Competing claim 13 allows for multiple doses to semiannually, or longer dosing periods. Note that this will dose several tissues which will not be physically damaged, so will inherently improve their performance. Furthermore, at some time, the subject will do some sort of exercise.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
response to applicant’s arguments
Applicants request that this rejection be held in abeyance until the claims are otherwise allowable. However, until the rejection is overcome, it will remain valid.
fourth rejection
Claims 1-3, 5, 8, 9, 13, 14, and 19-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of US Patent No. 11,197,912 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the competing claims anticipate the instant claims.
Competing claim 8 discusses a method to prevent or treat COVID-19, comprising administering MG53 over a period of up to 2 weeks.
response to applicant’s arguments
Applicants request that this rejection be held in abeyance until the claims are otherwise allowable. However, until the rejection is overcome, it will remain valid.
fifth rejection
Claims 1-3 and 5-19-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 7 of US Patent No. 7,981,866 (reference application) in view of McNeil et al (Am. J. Pathol. (1992) 140(5) p1097-1109) and Brilla et al (J. Exc. Physiol. (2000) 3(4) 26-36).
Competing claim 8 is a method of preventing or treating muscle cell damage, comprising administering MG53.
The difference between the competing claims and the examined claims is that the competing claims do not link the muscle damage to exercise.
McNeil et al discuss damage to muscles due to exercise, specifically, their plasma membrane (title). The reference clearly states that muscles are damaged by exercise (p1097, 2nd column, 1st paragraph). Note that, for there to be damage, the exercise must reasonably be considered strenuous. This reference links muscle damage to exercise.
Brilla et al discuss a zinc-magnesium supplement (title). Zinc monomethionine asparate, among other ingredients, were administered to football players, which increased muscle strength (abstract). Note that methionine can reasonably be considered an antioxidant.
Therefore, it would be obvious to treat the patients of McNeil et al with the therapy of the competing claims, to prevent or treat the muscle damage described by McNeil et al. As that reference discusses muscle damage, the same disorder that the competing claims are treating, an artisan in this field would attempt this therapy with a reasonable expectation of success.
Furthermore, it would be obvious to add the therapy of Brilla et al to the treatment of the competing claims, as Brilla et al teaches the therapy helps with muscle growth. As this is the same patient population, an artisan in this field would attempt this therapy with a reasonable expectation of success.
response to applicant’s arguments
Applicants request that this rejection be held in abeyance until the claims are otherwise allowable. However, until the rejection is overcome, it will remain valid.
sixth rejection
Claims 1-3 and 5-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of US Patent No. 9,458,465 (reference application) in view of McNeil et al (Am. J. Pathol. (1992) 140(5) p1097-1109) and Brilla et al (J. Exc. Physiol. (2000) 3(4) 26-36).
Competing claim 1 is a composition for treating a tissue damage injury or disorder, comprising administering MG53.
The difference between the competing claims and the examined claims is that the competing claims do not link the muscle damage to exercise.
McNeil et al discuss damage to muscles due to exercise, specifically, their plasma membrane (title). The reference clearly states that muscles are damaged by exercise (p1097, 2nd column, 1st paragraph). Note that, for there to be damage, the exercise must reasonably be considered strenuous. This reference links muscle damage to exercise.
Brilla et al discuss a zinc-magnesium supplement (title). Zinc monomethionine asparate, among other ingredients, were administered to football players, which increased muscle strength (abstract). Note that methionine can reasonably be considered an antioxidant.
Therefore, it would be obvious to treat the patients of McNeil et al with the therapy of the competing claims, to prevent or treat the muscle damage described by McNeil et al. As that reference discusses muscle damage, the same disorder that the competing claims are treating, an artisan in this field would attempt this therapy with a reasonable expectation of success.
Furthermore, it would be obvious to add the therapy of Brilla et al to the treatment of the competing claims, as Brilla et al teaches the therapy helps with muscle growth. As this is the same patient population, an artisan in this field would attempt this therapy with a reasonable expectation of success.
response to applicant’s arguments
Applicants request that this rejection be held in abeyance until the claims are otherwise allowable. However, until the rejection is overcome, it will remain valid.
New Rejections
Claim Rejections - 35 USC § 103
The legal basis for rejections under this statute was given above, and will not be repeated here.
Claim(s) 1-3 and 5-21 are rejected under 35 U.S.C. 103 as being unpatentable over McNeil et al (Am. J. Pathol. (1992) 140(5) p1097-1109, previously cited) in view of over Jia et al (Nat. Commun. (2014) 5:4387, previously cited), Brilla et al (J. Exc. Physiol. (2000) 3(4) 26-36, previously cited), Le Tourneau et al (J. Natl. Cancer Inst. (2009) 101 p708-720), and Xiao et al (US 20150361146, previously cited).
McNeil et al discuss disruption of muscle fiber cell membranes (title). Rats were exercised for 90 min on a treadmill (p1098, 1st column, 4th paragraph), and their muscle fibers extracted and fixed in formaldehyde (p1098, 2nd column, 1st paragraph). Additional experiments looked at materials injected into the rats that could penetrate the cell membrane that appear in the cells if it is compromised (p1101, 2nd column, 2nd paragraph, p1102, 1st column, 2nd paragraph, continues to 2nd column, 1st paragraph). If the rat had some time to recover, a small number of muscle fibers showed fiber necrosis and infiltration with fibroblasts, monocytes, and macrophages (p1101, 2nd column, 3d paragraph). Even small amounts of exercise sufficed to cause damage (p1107, 1st column, 2nd paragraph).
The difference between this reference and the examined claims is that this reference does not describe using MG53 therapy to heal the damaged muscle.
The teachings of McNeil et al are confirmed by Jia et al, who teach that mechanical stress of muscles and lungs causes plasma membrane disruptions (p2, 1st column, 1st paragraph). MG53 is a component of the membrane repair machinery in muscle tissue (p2, 1st column, 1st paragraph), and is also expressed in the lungs (2nd page, 1st column, 4th paragraph). Additional MG53 protected against such damage in culture of lung cells (5th page, 1st column, 2nd paragraph), and in vivo in a model of lung damage (p5, 2nd column, 2nd paragraph). This also ameliorated damage when administered afterwards (p5, 2nd column, 4th paragraph). This reference shows that MG53 will heal plasma membrane damage in lung tissue, and strongly suggests it will do so in muscle tissue.
Brilla et al discuss a zinc-magnesium supplement (title). Zinc monomethionine asparate, among other ingredients, were administered to football players, which increased muscle strength (abstract). Note that methionine can reasonably be considered an antioxidant. This reference discusses zinc and antioxidants as supplements to improve muscle performance.
Le Tourneau et al discusses phase 1 clinical trials (title). The main goal of these studies is to establish the dose and dose schedule for new drugs or drug combinations (abstract). A number of different methods to determine these parameters are given (fig 2, p711, top of page). This reference discusses optimizing the dose and dose schedule of drugs and drug combinations.
Xiao et al discuss mutated versions of MG53 (title). The most preferable mutated version has the 14th Cys residue in the Ring domain mutated to Ala (paragraph 18), which still had activity while avoiding some side effects (paragraph 19). This reference discusses variants of MG53.
Therefore, it would be obvious to use the MG53 of Jia et al to treat the muscle plasma membrane damage of McNeil et al, as Jia et al shows it will heal similar damage in lung tissue, and shows that the same pathway works in muscle tissue. As this protein is indigenously involved in repairing similar damage, according to Jia et al, an artisan in this field would attempt this therapy with a reasonable expectation of success.
Furthermore, it would be obvious to administer the supplement of Brilla et al, to increase the muscle mass of the exercisers. As this is used for a subgenus of these individuals, an artisan in this field would attempt this addition with a reasonable expectation of success.
In addition, it would be obvious to optimize the dose and dose schedule of the therapeutics to maximize therapeutic effect while minimizing side effects. As this process must be done for every drug and drug combination, an artisan in this field will be experienced enough to have a reasonable expectation of success in this optimization.
McNeil et al teach that exercise causes plasma membrane damage in muscle tissue. Jia et al suggests that MG53 will help repair the damage, rendering obvious claims 1-3, 8, 13, 14, 19, and 21.
Le Tourneau et al discusses optimizing the dose and dose schedule, rendering obvious claim 5.
Brilla et al renders obvious adding a zinc antioxidant formulation, rendering obvious claims 6, 7, 10-12, and 16-18.
Jia et al shows that the therapy is effective in a different cell type if administered either prophylactically or afterwards, rendering obvious claims 9 and 15.
Xiao et al discusses variants of MG53, which are obvious as a substitution of one known element for another yielding expected results, rendering obvious claim 20.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658