Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office Action has been withdrawn pursuant to 37 CFR 1.114.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 December 8, 2025 has been entered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Status of Claims
Claims 1, 9 – 10, 12 – 13, 22 – 25, 27 – 28, and 33 - 34 are currently pending. Claims 1, 13, and 22 have been amended in the Applicant’s amendment filed November 10, 2025. Claim 31 has been canceled in the Applicant’s amendment filed November 10, 2025. Claim 34 has been added in the Applicant’s amendment filed November 10, 2025.
Applicant's election of Group I, claims 1 – 10, 12, 13 and 18, drawn to a scaffold-cell construct; and the election of Species as follows:
Species (A): wherein the first cell population is a skeletal myocyte-derived cell (claim 6), in the reply filed February 15, 2023 was previously acknowledged.
Claims 19 and 21 – 26 (claims 19, 21 and 26 were previously canceled) were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claim 34 is newly withdrawn, as it depends on withdrawn claim 22.
The restriction requirement was previously made FINAL.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election of invention was previously treated as an election without traverse
(MPEP § 818.03(a)).
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1, 9 – 10, 12 – 13, 27 – 28, and 33 are under consideration to which the following grounds of rejection are applicable.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on May 26, 2026 have been considered. Initialed copies of the IDSs accompany this Office Action.
Withdrawn Objections/Rejections
Claim Rejection - 35 USC § 112(b)
The rejection of claims 1, 9 – 10, 12 – 13, 27 – 28, 31, and 33 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 is withdrawn.
Claim 1 has been amended to overcome the indefiniteness rejection.
In view of the withdrawn rejection, Applicant’s arguments are moot.
Claim Rejections - 35 USC § 103
The rejection of claims 1, 9 – 10, 12, 13, 27 – 28, and 31 and 33 under 35 U.S.C. 103 as being unpatentable over Amer et al. (hereinafter referred to as “Amer”) (Amer LD. Et al Tissue engineering approaches to cell-based type 1 diabetes therapy. Tissue Eng Part B Rev. 2014 Oct;20(5):455-67. doi: 10.1089/ten.TEB.2013.0462. Epub 2014 Apr 22. PMID: 24417705; PMCID: PMC4185974.) and further in view of Huang et al.. (hereinafter referred to as “Huang”) (Huang C. et al. Sustained exposure of L6 myotubes to high glucose and insulin decreases insulin-stimulated GLUT4 translocation but upregulates GLUT4 activity. Diabetes. 2002 Jul;51(7):2090-8. doi: 10.2337/diabetes.51.7.2090. PMID: 12086937.), as evidenced by Gimble et al. (US Patent Application Publication US 2008/0038236 A1. Published Feb 14, 2008) is withdrawn.
Amer and Huang do not teach stimulating the cells with insulin and restoring the glucose levels in a subject having type 2 diabetes mellitus (amended claim 1).
In view of the withdrawn rejection, Applicant’s arguments are moot.
New Objections/Rejections
Claim Rejections - 35 USC § 112(a) - Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112, first paragraph:
(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, 9 – 10, 12, 13, 27 – 28, and 31 and 33 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1, 9 – 10, 12, 13, 27 – 28, and 33 encompass a pharmaceutical composition comprising a porous scaffold-cell construct, comprising a) a porous scaffold comprising at least one biocompatible polymer, and b) a cell population on or in said porous scaffold comprising myoblast cells overexpressing an exogenous polynucleotide encoding Glut4 compared to control wild type myoblast cells, thereby having increased Glut4 activity compared to the control wild type myoblast cells, wherein when stimulated with insulin, said myoblast cells exhibit enhanced glucose uptake compared to the control wild type myoblast cells, and wherein said construct is present in said pharmaceutical composition in an amount effective for restoring glucose levels in a subject having type 2 diabetes mellitus administered therewith to glucose homeostasis of a healthy subject. Overall, what these statements indicate is that the Applicant must provide adequate description of such core structure and function related to that method such that the Artisan could determine the desired effect. Hence, the analysis below demonstrates that Applicant has not determined the core structure and function for full scope of the claimed method.
There is not structure/ function relationship for the claimed pharmaceutical compositions comprising: any biocompatible polymers, any amount of seeded myoblast cells overexpressing an exogenous polynucleotide wherein, when stimulated with insulin, said myoblast cells exhibit enhanced glucose uptake and wherein said porous scaffold-cell construct is present in said pharmaceutical composition in an amount effective for restoring glucose levels in a subject having type 2 diabetes mellitus administered therewith,. to glucose homeostatic levels of a healthy subject. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail such that the Artisan can reasonably conclude that the inventors had possession of the claimed invention. Such possession may be demonstrated by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and/or formulae that fully set forth the claimed invention. Possession may be shown by an actual reduction to practice, showing that the invention was "ready for patenting", or by describing distinguishing identifying characteristics sufficient to show that Applicant was in possession of the claimed invention (January 5, 2001 Fed. Reg., Vol. 66, No. 4, pp. 1099-11). MPEP § 2163.II.A.3.(b) states, “when filing an amendment an applicant should show support in the original disclosure for new or amended claims” and “[i]f the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112, para. 1, as lacking adequate written description”. Moreover, MPEP 2163 states: [A] biomolecule sequence described only by a functional characteristic, without any known or disclosed characteristic, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence. An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function.
In analyzing whether the written description requirement is met for the claimed method, it is first determined whether the examples teach encompass a pharmaceutical composition comprising a porous scaffold-cell construct, comprising a) a porous scaffold comprising at least one biocompatible polymer, and b) a cell population on or in said porous scaffold comprising myoblast cells overexpressing an exogenous polynucleotide encoding Glut4 compared to control wild type myoblast cells, thereby having increased Glut4 activity compared to the control wild type myoblast cells, wherein when stimulated with insulin, said myoblast cells exhibit enhanced glucose uptake compared to the control wild type myoblast cells, and wherein said construct is present in said pharmaceutical composition in an amount effective for restoring glucose levels in a subject having type 2 diabetes mellitus administered therewith to glucose homeostasis of a healthy subject.
In the instant case, Applicant discloses two relevant examples. In Example 2 of the as-Filed Specification, the Applicant teaches that L6WT myoblasts and L6Glut4 myoblasts were seeded in scaffolds, and the scaffolds were then incubated in the presence or absence of insulin (Paragraph [0177]). At a concentration of 0.5x 106 a significantly higher insulin stimulated uptake rate was noted in the L6GLUT4 samples compared to L6WT (Paragraph [0178]). This example teaches stimulating the myoblast cells at a concentration of 0.5x 106 followed by stimulation with insulin, that the myoblast cells exhibit enhanced glucose uptake at a specific concentration, but does not teach restoring glucose levels in a subject having type 2 diabetes mellitus.
Further, Example 3 teaches glucose uptake in vivo, wherein 18 male mice that have a DM2 (diabetes mellitus 2) phenotype received constructs seeded with Glut4 overexpressing L6 cells (Paragraph [0181]). The mice which were implanted with GLUT4, showed better tolerance to glucose load compared to control mice, and their blood glucose levels returned to the basal-normal level faster compared to the control group (Paragraph [0181]). While this example teaches restoring glucose levels in male mice having type 2 diabetes mellitus, it does not teach stimulating the myoblast cells with insulin.
Before the effective filing date of the claimed invention, tissue engineering approaches were known in the art, wherein insulin producing cells were cultured with ECM molecules in 3D constructs to enhance the efficacy of cell-based therapies for diabetes, specifically type 1 diabetes, as evidenced by Amer et al. (Abstract).
The applicant is on record for saying that the composition would not be used for patients with type 2 diabetes as patients have no need for insulin-producing cells (Remarks, pg. 8, last paragraph). Thus, it was known in the art that such 3D constructs comprising scaffolds are not used for restoring glucose levels in a subject having type 2 diabetes mellitus.
Furthermore, it was known in the art that L6 myotubes offer the possibility of analyzing the different steps of glucose uptake and compare Glut4 translocation to glucose uptake, as taught by Huang et al. (right column, first full paragraph). Huang teaches that Glut4 determines glucose uptake in L6 myotubes overexpressing myc-tagged Glut4, wherein the Glut4 myc myoblasts were differentiated into myotubes (Abstract).
The applicant is on record for saying that Huang uses its cells only as in vitro models of high glucose and insulin state to allow understanding of the molecular basis of acquired insulin resistance and has no suggestion that such cells can be used as a treatment for any type of diabetes (Remarks, pg. 12). Thus, myoblasts are only used to study glucose uptake and not used as treatments for diabetes.
Additionally, it was known in the art that Expression of the insulin-regulated glucose transporter GLUT4 is minimal in human myoblasts in culture, and glucose uptake was essentially insensitive to insulin, as evidenced by Hurel et al. (Hurel SJ. Et al.Biochem J. 1996 Dec 15;320 ( Pt 3)(Pt 3):871-7. doi: 10.1042/bj3200871. PMID: 9003374; PMCID: PMC1218009.) (pg. 874, left column, third paragraph). The applicant also is on record for saying that there is no significant difference between the insulin stimulated uptake rates for the L6WT and L6GLUT4 constructs was observed (Paragraph [0178]). Thus, myoblast cells, when stimulated with insulin, do not exhibit enhanced glucose uptake.
There is no structure/function correlation for all the claimed composition. In the instant case, Applicant does not disclose any relevant examples that teach the composition a porous scaffold comprising at least one biocompatible polymer, a cell population comprising myoblast cells overexpressing an exogenous polynucleotide encoding GLUT4, and when stimulated these cells with insulin, the myoblasts cells restore glucose levels in a subject having type 2 diabetes mellitus to the glucose homeostatic levels of a healthy subject.
Therefore, the specification does not contain a written description of the invention, and a 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 can make and use the same, nor does it set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. This limited information is not deemed sufficient to reasonably convey to one skilled in the art that Applicant is in possession of the method of culturing natural killer cells as recited in the instant claims.
Claim Rejection - 35 USC § 112(a) Scope of Enablement
Claims 1, 9 – 10, 12, 13, 27 – 28, and 33 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 pharmaceutical composition comprising a porous scaffold-cell construct, comprising a) a scaffold comprised of PLLA/PLGA (poly-l-lactic acid/ polylactic glycolic acid), and b) a cell population, comprising 0.25x 106 cells, on or in said porous scaffold comprising myoblast cells overexpressing an exogenous polynucleotide encoding Glut4 compared to control wild type myoblast cells, thereby having increased Glut4 activity compared to the control wild type myoblast cells, wherein when stimulated with insulin, said myoblast cells exhibit enhanced glucose uptake compared to the control wild type myoblast cells, and wherein said construct is present in said pharmaceutical composition in an amount effective for restoring glucose levels in a subject having type 2 diabetes mellitus administered therewith to glucose homeostasis of a healthy subject, d
does not reasonably provide enablement for a scaffold comprised of any biocompatible polymer or culturing any concentration of myoblast cells overexpressing Glut4. The Specification does not enable any person skill 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 claims, when given the broadest possible interpretation, encompass a method of expressing a peptide in an immune cell, comprising (i) introducing RNA encoding the peptide into the immune cell, and (ii) providing a Toscana virus NSs protein to the immune cell. 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 test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the patent coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is required is not based on a single factor but is rather a conclusion reached by weighing many factors (See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter, 1986) and In re Wands, 8USPQ2d 1400 (Fed. Cir. 1988); these factors include the following:
Nature of invention. The invention encompasses a pharmaceutical composition
comprising a pharmaceutical composition comprising a porous scaffold-cell construct, comprising a) a porous scaffold comprising at least one biocompatible polymer, and b) a cell population on or in said porous scaffold comprising myoblast cells overexpressing an exogenous polynucleotide encoding Glut4 compared to control wild type myoblast cells.
Scope of the invention. The invention encompasses a pharmaceutical composition that is
administered to reduce glucose levels in a subject with type 2 diabetes.
Number of working examples and guidance. In the instant case, Applicant provides two
relevant working examples. First, the as-Filed Specification teaches the scaffold fabrication (Paragraph [0166]). The porous biodegradable scaffolds were made using poly-l-lactic acid (PLLA; Polysciences, Warrington) and polylactic glycolic acid (PLGA; Boehringer Ingelheim), using both the polymers in a 1:1 ratio (Paragraph [0166]). This example only teaches the use of a PLLA/PLGA scaffold, and does not teach the use of any other polymers.
In Example 2 of the as-Filed Specification, the Applicant teaches that L6WT myoblasts and L6Glut4 myoblasts were seeded in scaffolds, and the scaffolds were then incubated in the presence or absence of insulin (Paragraph [0177]). Upon seeding of 0.25×10.sup.6 cells per scaffold, the stimulated uptake by the L6GLUT4 cells was significantly higher compared to the basal uptake rate for L6GLUT4 (Paragraph [0178]). At a concentration of 0.5x 106 a significantly higher insulin stimulated uptake rate was noted in the L6GLUT4 samples compared to L6WT (Paragraph [0178]). Thus, there is a minimum concentration of 0.25x 106 cells that is need to have the desired result of higher uptake of glucose compared to the basal uptake rate.
4) State of the art. Although the field of expressing reducing glucose levels in a subject is highly developed, the use of biocompatible scaffolds comprising polymers and myoblast cells for reducing glucose levels is not highly developed. Unpredictability of the art. Before the effective filing date of the claimed invention, tissue engineering approaches were known in the art, wherein insulin producing cells were cultured with ECM molecules in 3D constructs to enhance the efficacy of cell-based therapies for diabetes, specifically type 1 diabetes, as evidenced by Amer et al. (Abstract).
The applicant is on record for saying that the composition would not be used for patients with type 2 diabetes as patients have no need for insulin-producing cells (Remarks, pg. 8, last paragraph). Thus, it was known in the art that such 3D constructs comprising scaffolds are not used for restoring glucose levels in a subject having type 2 diabetes mellitus.
Furthermore, it was known in the art that L6 myotubes offer the possibility of analyzing the different steps of glucose uptake and compare Glut4 translocation to glucose uptake, as taught by Huang et al. (right column, first full paragraph). Huang teaches that Glut4 determines glucose uptake in L6 myotubes overexpressing myc-tagged Glut4, wherein the Glut4 myc myoblasts were differentiated into myotubes (Abstract).
The applicant is on record for saying that Huang uses its cells only as in vitro models of high glucose and insulin state to allow understanding of the molecular basis of acquired insulin resistance and has no suggestion that such cells can be used as a treatment for any type of diabetes (Remarks, pg. 12). Thus, myoblasts are only used to study glucose uptake and not used as treatments for diabetes.
Additionally, it was known in the art that Poly-L-lactic acid (PLLA) and poly-glycolic acid (PGA) exhibit a high degree of crystallinity and degrade relatively slowly, while copolymers of PLLA and PGA, PLGAs, are amorphous and rapidly degraded, as evidenced by Kaplan et al. (US 20080280360 A1, published November 13, 2008) (Paragraph [0048]). Kaplan et al. also teaches that PLGA is a preferable polymeric material as it is biocompatible and biodegradable (Paragraph [0048]).
Amount of Experimentation Required. Given the unpredictability of the art, the poorly
developed state of the art with regard to using scaffolds are not used for restoring glucose levels in a subject having type 2 diabetes mellitus, the use of myoblasts only to study glucose uptake, and the variability in the polymers used in the biocompatible scaffold, the skilled artisan would have to conduct undue, and unpredictable experimentation to practice the claimed invention using the pharmaceutical composition, and reduce glucose levels in a subject with T2D.
Conclusion
Claims 1, 9 – 10, 12, 13, 27 – 28, and 33 remain rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VYOMA SHAILESH THAKKER whose telephone number is (571)272-2954. The examiner can normally be reached M-F 8:30 - 5:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached on (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/VYOMA SHUBHAM TIWARI/ Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634
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