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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/22/25 has been entered.
The amendment filed on 12/22/25 added new claim 21.
Election/Restrictions
Upon further consideration, claims 12-17 have been rejoined with the elected invention and examined.
Claims 18-20 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/14/24.
Response to Arguments
Applicant’s arguments, see pages 5-6, filed 12/22/25, with respect to 112a written description rejection have been fully considered and are persuasive. The rejection of claims 1, 4-8 and 11 has been withdrawn because of the amendment to the independent claims to limit the CD82 sequence to human CD82 polypeptide sequence comprising about 95% to SEQ ID NO: 1 or 2.
Applicant’s arguments, see pages 6-8, filed 12/22/25, with respect to 102 rejection have been fully considered and are persuasive. The rejection of claim 9 has been withdrawn because of the removal of dexamethasone. However, upon further consideration, a new ground(s) of rejection is made in view of the removal of dexamethasone from claim 9 and the addition of new claim 21 and updated search for sodium pyruvate.
Applicant’s arguments, see pages 6-8, filed 12/22/25, with respect to 103 rejection based on MODERNATX (WO2018157009) and Alsobrook (US 20040067882) have been fully considered and are persuasive because the inventors made the “surprising discovery that creatine kinase (CK), a marker for muscle damage is markedly reduced in dystrophic mice overexpressing CD82 relative to CK levels in control dystrophic mice (paragraph 75 of the specification).” Thus, the use of CD82 in the claimed method of preserving or increasing muscle function, repairing a cell membrane, or of increasing and/or enhancing myofiber structure in a muscle cell or a muscle progenitor cell in a dystrophic mice was an unexpected discovery because of the over-expression of CD82 in dystrophic mice produced a stunning reduction in CK levels to levels that were just slightly greater than that observed in the control mice (Table 1). The 103 rejection of claims 1, 4-8, and 11 has been withdrawn. However, upon further consideration a new rejection under 112a is required for claims 1, 5-8 and 11.
Thus, instant claim 4 is in condition for allowance.
Claim Interpretation
The term “the CD82 polypeptide(polynucleotide)” in claim 1 and dependent claims 5-7 is limited to human CD82 polypeptide because the claims depend on claim 1 which limits the CD82 to a human CD82 polypeptide having about 95% amino acid sequence to SEQ ID NO: 1 or 2 or a polynucleotide encoding the human CD82 polypeptide. Thus, the claims boundaries of the term ‘CD82 polypeptide(polynucleotide)’ is clear and further limit the claim from which they depend from. If applicant wanted to they could amend the claims to recite the human polypeptide/polynucleotide to make the claims consistent with the use of the term.
The pre-amble of Claims 13 and 14 and claims 15 and 17 refer to the expression vector of claim 12 and one of ordinary skill in the art would understand that it refers to the mammalian expression vector in the independent claim 12 because there is only one vector in claim 12. In addition, it does not read on a vector that would be broader than and encompass a mammalian expression vector. Thus, the claim boundaries of the term “expression vector” are clear and further limit the claim from which they depend from. Applicant could amend the claim to recite the mammalian expression vector to make the limitation in the claims consistent with the use of the term.
Claim Objections
Claim 17 is objected to because of the following informalities: Should pharmaceutic in line 1 be pharmaceutical?
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claims 15 and 16 are rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). The broadest reasonable interpretation of the claimed product is a human comprising the cell because the expression vector can be used to treat muscular dystrophy in a human. Thus, when the vector is delivered to a human the human would be embraced by the claimed product. Suggest amending the claim to recite “An isolated mammalian cell” to overcome the 101 rejection.
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 1, 5-8 and 11 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 a method comprising administering to a dystrophic cell or a muscle cell or muscle progenitor cell a human CD82 polypeptide or polynucleotide encoding the human CD82 polypeptide, wherein the human CD82 polypeptide having about 95% amino acid sequence identity to SEQ ID NO: 1 or 2, thereby preserving or increasing muscle function in the dystrophic cell or repairing a cell membrane or myofiber structure in the muscle cell or muscle progenitor cell, does not reasonably provide enablement for using the method in a genus of cells. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The claimed method broadly embraces administering a human CD82 polypeptide or polynucleotide encoding the human CD82 polypeptide, wherein the human CD82 polypeptide having about 95% amino acid sequence identity to SEQ ID NO: 1 or 2 to a genus of cells, wherein preserving or increasing muscle function in a dystrophic cell or repairing a cell membrane or myofiber structure in the muscle cell or muscle progenitor cell. The method step in instant claim 1 is delivering to a cell, while the pre-amble and the functional limitations are limited to a dystrophic cell or muscle cells or muscle progenitor cells.
The specification contemplates increasing expression of CD82 in one or more cells of a subject, wherein the cell is a muscle cell (myofibers), satellite cells, myoblasts, muscle side population cells, fibroblast cells, smooth muscle cells, blood cells, blood vessel cells, stem cells, mesenchymal stem cells, and neurons (page 16).
The specification provides working examples of expression of CD82 in muscle cells increases or enhances muscle cell membrane integrity (pages 22-23). Muscle tissue and muscle cells from DMD patients was analyzes and showed that CD82 protein was significantly lower (Figs. 1B and 1D). “Dystrophic cells are clearly different than control fetal and adult cells (page 28).” CD82 expression is absent. Mice lacking CD82 did not display the same regenerative ability as healthy control mice (example 2). Muscle strength is reduced in dystrophic mice lacking CD82 (Example 3). Example 4 showed over-expression of CD82 in dystrophic mice produced stunning reduction in CK levels. CK is used to measure muscle cell damage in early stages of DMD. Overexpression of CD82 appeared to at least partially rescue the histological muscle phenotype observed in dystrophic muscle (Figure 10).
A skilled artisan with knowledge of the relevant art at the time of the effective filing date would possess the knowledge that CD82 is a metastasis suppressor gene product is a membrane glycoprotein that is a member of the tetraspanin/transmembrane 4 superfamily and plays a key role in endometriosis. CD82 is also known as KAI1.
The prior art appears to disclose that CD82 expression is associated with muscular dystrophy. See Alexander et al. (Cell Stem Cell 2016, 19, 800-807); Yamanaka et al. (International Journal of Molecular Science, 2019, 20, 1-11; and Termini et al. (Molecular Biology of the Cell, 25, 1560-1573, 2014), all cited on an IDS.
With respect to muscular dystrophy (MD) nucleic acid/protein therapy, the prior art of record teaches that ex vivo and in vivo gene therapy have been used to treat MD. For example, see WO 2018/157009 and WO 2018/0191282, both cited on an IDS. WO 2018/157009 discloses a list of proteins that might be able to alleviate one or more symptoms of a muscular disease or dystrophy, including in the list is CD82 (page 15).
As stated above, the method step in instant claim 1 embraces delivering to a cell, while the pre-amble and the functional limitations are limited to a dystrophic cell or muscle cells or muscle progenitor cells. A dystrophic cell would indicate to one of skill in the art that the cell is limited to cell exhibiting structural of functional abnormalities due to absence or malfunction of dystrophin, but a cell used in the method step is broader than dystrophic cell. Neither the specification nor the prior art of record disclose that administering a human CD82 polynucleotide or a human CD82 polypeptide would result in preserving or increasing muscle function in a genus of cells. In view of the teaching in the prior art combined with the working examples in the specification, the claimed method is only enabled for using dystrophic cells, muscle or muscle progenitor cells in the method.
Thus, the claimed method is only enabled for administering the human CD82 polynucleotide or polypeptide to dystrophic cells, muscle cells or muscle progenitor cells.
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.
Claim 6 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 6 recites the limitation "a CD82 polynucleotide" in line 1. There is insufficient antecedent basis for this limitation in the claim. The limitation should recite the CD82 polynucleotide to be consistent with the term in claim 5.
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.
Claims 12, 15, and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dong et al. (US 6204000).
Dong et al. disclose:
Production of recombinant KAI1 protein or a fragment thereof may be directed by a natural or synthetic nucleic acid sequence inserted into a suitable expression vector. A preferred nucleic acid sequence is the KAI1 cDNA sequence shown in SEQ ID NO: 19. In one embodiment, restriction digest fragments containing the full-length cDNA or fragments thereof containing a coding sequence for KAI1 can be inserted into a suitable expression vector. By suitable expression vector is meant a vector that can function in eukaryotic or prokaryotic cells and is capable of carrying and expressing a nucleic acid sequence encoding the KAI1 protein or a fragment thereof
The present invention also relates to a gene therapy method in which an expression vector containing a nucleic acid sequence representing the wild-type KAI1 gene is administered to a subject having a mutation of the KAI1 gene. A nucleic acid sequence representing wild-type KAI1 gene is that shown in SEQ ID NO: 19. Such nucleic acid sequence may be inserted into a suitable expression vector by methods known to those of ordinary skill in the art. Expression vectors suitable for producing high efficiency gene transfer in vivo include retroviral, adenoviral and vaccinia viral vectors. See column 8 and 12.
KAI1 gene is another term (alias) for the CD82 gene. In addition, SEQ ID NO: 20 (Qy) of Dong et al. has the same sequence as designated by the instant application for the sequence encoding be the human CD82 gene (SEQ ID NO: 1, Qy).
PNG
media_image1.png
304
627
media_image1.png
Greyscale
The specification does not disclose an effective amount of the expression vector, thus any amount taught by Dong et al. anticipates the limitation.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Tanaka et al. (Science Direct 7, 399-403, 2007) taken with Exerkine Corporation (WO 2016/115632).
Tanaka teaches a therapeutic potential of pyruvate therapy for mitochondrial diseases (pages 399-401). Tanaka administered 5 grams of sodium pyruvate to a patient with chronic progressive external opthalmoplegia (CPEO) carrying deletion of mitochondrial DNA (page 401).
Tanaka et al. does not specifically teach using sodium pyruvate to treat a subject having or suspected of having muscular dystrophy (MD).
However, a person of ordinary skill in the art would possess the knowledge that MD can be considered a secondary mitochondrial disease as taught by Exerkine Corp (paragraph 70).
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to combine the teaching of Tanaka et al. taken with Exerkine Corp. to use sodium pyruvate in a method for treating MD with a reasonable expectation of success, namely to arrive at the claimed invention. See MPEP 2143(I)B or G. One of ordinary skill in the art would have been motivated to combine the teaching to use the sodium based pyruvate to increase solubility, stability and absorption of pyruvate in the bloodstream of said subject. See also MPEP 2141(II)C. Rationales to support rejections under 35 U.S.C. 103 recites, “Prior art is not limited to the references being applied, but includes the understanding of one of ordinary skill in the art.”
MPEP 2141. FACTORS TO CONSIDER IN DETERMINING LEVEL OF ORDINARY SKILL
The person of ordinary skill in the art is a hypothetical person who is presumed to have known the relevant art at the relevant time. Factors that may be considered in determining the level of ordinary skill in the art may include: (1) "type of problems encountered in the art;" (2) "prior art solutions to those problems;" (3) "rapidity with which innovations are made;" (4) "sophistication of the technology; and" (5) "educational level of active workers in the field." In re GPAC, 57 F.3d 1573, 1579, 35 USPQ2d 1116, 1121 (Fed. Cir. 1995). "In a given case, every factor may not be present, and one or more factors may predominate." Id. See also Custom Accessories, Inc. v. Jeffrey-Allan Indust., Inc., 807 F.2d 955, 962, 1 USPQ2d 1196, 1201 (Fed. Cir. 1986); Environmental Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696, 218 USPQ 865, 868 (Fed. Cir. 1983).
.
While the specification of the instant disclosure contemplates the limitation "effective amount" in clam 9 it does not define any amount for the limitation. Tanaka teaches that the pyruvate can be used to treat muscular dystrophy in a human subject. Thus, the limitation is considered very broad because it embraces any amount that treats muscular dystrophy would read on the limitation.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Tanaka taken with Exerkine Corp. as applied to claim 9 above, and further in view of Fenichel (WO 98/24449, of record).
Tanaka and Exerkine do not specifically teaching combining either an effective amount of either dexamethasone or oxandrolone with sodium pyruvate to treat MD.
However, Fenichel teaches treating muscular dystrophy in a patient comprising administering oxandrolone to the patient (page 13). Fenichel teaches that oxandrolone can be administered to treat muscular dystrophy in amount about 0.05 to 2.0 mg/kg/day.
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to combine the teaching of Tanaka and Exerkine Corp. taken with Fenichel to combine oxandrolone with sodium pyruvate in a method of treating MD, namely to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to combine the teaching to observe an additive effect for treating MD in the subject.
While the specification of the instant disclosure contemplates the limitation "effective amount" in new clam 21 it does not define any amount for the limitation. Fenichel teaches that a certain amount of oxandrolone can be used to treat muscular dystrophy in a subject. Thus, the limitation is very broad because it reads on any amount that treats one or more symptoms of muscular dystrophy would read on the limitation.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Tanaka taken with Exerkine Corp. as applied to claim 9 above, and further in view of (US2016030255, of record).
Tanaka and Exerkine do not specifically teaching combining either an effective amount of either dexamethasone or oxandrolone with sodium pyruvate to treat MD.
However, '255 teaches that dexamethasone is a corticosteroid and can be used in a method to treat muscular dystrophy (MD) (paragraph 177). An 'effective amount' is not defined by the instant specification and '255 teaches that corticosteroid (for example dexamethasone) are known to treat MD. Thus, in view of the broadest reasonable interpretation of the term, any amount of dexamethasone administered to a subject having muscular dystrophy would read on the limitation.
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to combine the teaching of Tanaka and Exerkine Corp. taken with ‘255 to combine dexamethasone with sodium pyruvate in a method of treating MD, namely to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to combine the teaching to observe an additive effect for treating MD in the subject. While the specification of the instant disclosure contemplates the limitation "effective amount" in new clam 21; it does not define any amount for the limitation. ‘255 teaches that a certain amount of dexamethasone can be used to treat muscular dystrophy in a subject. Thus, the limitation is very broad because it reads on any amount that treats one or more symptoms of muscular dystrophy would read on the limitation.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Claims 13, 14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Dong et al. (supra) as applied to claims 12, 15, and 17 above, and further in view of Modernatx (WO 2018157009, of record) and Mendell et al. (US 20140323956, of record).
Dong et al. teach human CD82 polypeptide and expression vectors suitable for producing high efficiency gene transfer in vivo include retroviral, adenoviral and vaccinia viral vectors. However, Dong et al. does not specifically teach an expression vector comprising an actin promoter operably linked to the polynucleotide encoding human CD82.
'009 teaches delivering a mRNA to mammalian cells (liver, spleen, muscle, or femur) to express a protein of interest (for example, see pages 9 and 16). Pages 14-15 of '009 disclose muscle therapeutic protein therapy to promote or support muscle maintenance or development and includes alleviating one or more symptoms of a muscle disease or dystrophy. CD82 protein is one of the proteins, which can be used in the method.
In addition, Mendell teaches using adeno associated viral (AAV) vectors (a mammalian expression vector) to deliver a nucleic encoding a protein to a subject to treat muscular dystrophy (page 19). Page 3 discloses using a muscle-specific promoter (e.g., actin promoter) to express the protein from the vector.
It would have been prima facie obvious to a person of ordinary skill in the art at the time the effective filing date to combine the teaching of Dong taken with '009 and Mendell to use a mammalian expression vector to deliver the human CD82 polypeptide to the muscle cells to study expression of CD82 polypeptide for treatment of muscle disorders, namely to arrive at the claimed invention. A person of ordinary skill in the art would have been motivated to use an AAV vector to assist in delivery of the nucleic acid encoding CD82 protein to muscle cells. It would have been a simple substitution to use AAV vector comprising a nucleotide sequence encoding the CD82 polypeptide with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to combine the teaching to use a muscle-specific (actin) promoter in the vector to control expression of the human CD82 protein and assists in delivery of the CD82 to the muscle cells.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the time of the effective filing date.
Conclusion
See attached PTO-326 for disposition of claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian Whiteman whose telephone number is (571)272-0764. The examiner can normally be reached on Monday thru Friday; 6:00 AM to 3:00PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at (571)-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/BRIAN WHITEMAN/ Primary Examiner, Art Unit 1636