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 .
Election/Restrictions
Applicant’s election of Group (I), with the addition of dihydrotestosterone for the single disclosed bioactive molecule upregulating GLP-1R species, Type-2 diabetes for the single disclosed subject population species and laparoscopic access as the single disclosed local administration species in the reply filed on 06/15/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 specifying traverse.
Priority
This application is a U.S. National Stage Application pursuant to 35 U.S.C. § 371 of International Patent Application PCT/1B2022/000517, filed on September 14, 2022, and published as WO 2023/041980 on March 23, 2023, which claims priority to PCT Patent Application PCT/FR2021/051573, filed on September 14, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/24/2024 and 04/03/2025 has been considered by the examiner.
Status of Claims
Claims 1-27 are pending. Claims 1-14 are withdrawn. Claims 15-27 are examined in accordance to the elected species.
Claim Objections
Claims 18-20 and 25 are objected to because the claims employ terms such as “preferably,” “more preferably,” and “yet more preferably” in the body of the claims. Such language described preferred embodiments rather then positively defining the metes and bounds of the claimed invention. Patent claims are required to point out and distinctly claim the subject matter regarded as the invention. The use of multiple preferred alternatives within a single claim renders it unclear which limitation Applicant intends to define as the claimed subject matter. Appropriate correction is required.
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 15-24 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 treating insulin resistance and/or restoring glucose homeostasis in a type-2 diabetic subject using dihydrotestosterone, does not reasonably provide enablement for the full scope of the claimed invention without undue experimentation.
Independent claims 15 and 26 broadly encompass any biological molecule capable of upregulating GLP-1 receptor (GLP-1r) expression, administered locally to the peri-portal region for treating insulin resistance and/or restoring glucose homeostasis. The claims also broadly encompass any subject in need of restoration of glucose homeostasis.
The specification, however, provides only a single working example employing one androgen, namely dihydrotestosterone (DHT), administered locally within the peri-portal region of obese insulin-resistant mini-pigs. No working examples are provided for other bioactive molecule and other subject in need thereof encompassed by the claims. Consequently, the breadth of the claims greatly exceeds the scope of enabling disclosure.
Wands factors identified in re Wands, 858 F.2d731 (Fed. Cir. 1998), weigh strongly in favor of nonenablment.
Breadth of the claims
The claims encompass virtually any molecule capable of increasing GLP-1 receptor expression and any subject in need of treatment of insulin resistant and/or restoring homeostasis. Such molecules include, but not limited to steroids, androgens, steroid analogs, functional variances, peptides, proteins, antibodies, antibody fragments, nucleic acids, mRNA, siRNA, antisense oligonucleotides, CRISPR-based systems, viral vectors, nanoparticles, transcriptional regulators, receptor trafficking modulators, epigenetic regulators, small molecules, biologics, and numerous other pharmacological agents. Such subject in need of restoration of glucose homeostasis includes, but not limited to metabolic syndrome, type-1 diabetes, type-2 diabetes, hypoglycemia, neuropathy, nephropathy, retinopathy, cardiovascular disease, and numerous other subjects. The claims therefore, encompass an extraordinarily large unpredictable genus.
Nature of the invention
The invention concerns regulation of GLP-1 receptor expression within the peri-portal region of the portal vein in order to improve glucose sensing and insulin resistance. The biological mechanism controlling GLP-1 receptor transcription, receptor trafficking, receptor internalization, receptor recycling, receptor degradation, and receptor signaling are highly complex. Whether a particular molecule increases receptor density within the peri-portal region cannot be predicted solely from its chemical structure. Instead, such activity depends upon numerous biological variables including receptor signaling, intracellular trafficking, tissue penetration, pharmacokinetics, pharmacodynamics, androgen receptor signaling, local metabolism, inflammatory status, gene regulation, and numerous biological pathways.
Moreover, the claims are not limited to subjects having type-2 diabetes, the only disease exemplified by Applicant. Rather, the claims encompass any subject in need of restoration of glucose homeostasis, which includes subjects suffering from numerous disease states or disorders. Because these disorders arise from different etiologies and pathogenic mechanism, a therapeutic approach demonstration only for the peri-portal administration of DHT in an insulin resistant mini-pig model would not reasonably establish that every bioactive molecule capable of upregulating GLP-1 receptor expression will restore glucose homeostasis across the full scope of the claimed subject population without undue experimentation. Accordingly, the claimed technology resides within an unpredictable art.
State of the prior art
The prior art demonstrates that DHT is capable of increasing GLP- 1 receptor expression. For example, Zhu et al. (Biomedicine & Pharmacotherapy 120 2019 109555, pages 1-12) reports that androgen signaling can increase GLP-1 receptor expression and such increased occurs with the treatment of DHT. (See Abstract) Likewise, AL-Noshokaty et al. (Toxicology Reports, Volume 14, June 2025, 101895) discusses regulation of GLP-1 receptor expression through complex transcriptional and signaling pathway involving numerous regulatory mechanisms. (See Abstract and Title.) AL-Noshokaty et al. demonstrates lixisenatide, a clinically used GLP-1 receptor agonist, was well-tolerated, yet failed to produced significant improvements in glycemic indices in that clinical setting. (See page 7, last paragraph, right column.). AL-Noshokaty et al. further explains that although GLP-1 receptor agonists have biological activity, clinically efficacy varies substantially depending upon the patient population, disease state, and clinical endpoint, and improvements in glucose-related outcomes are not uniformly observed. (See Page 18, Section 7.2.1, fourth paragraph.) Those teachings demonstrate that even direct pharmacologic activation of GLP-1R in humans does not necessarily restore glucose homeostasis or improve insulin resistance across patient populations, further illustrating the unpredictability of extrapolating Applicant’s single DHT example to the broad genus of claimed bioactive molecules and claimed subjects.
Guidance in the specification
Although the specification provides extensive discussion concerning insulin resistance, glucose homeostasis, GLP-1 receptors, portal glucose sensing, imaging, local administration and peri-portal anatomy, the specification provides very little guidance regarding how one identifies additional bioactive molecules possessing the required functional activity and additional subject populations. Outside of DHT and type-2 diabetes, the specification merely lists broad categories of possible molecules and subject populations without providing experimental data demonstration that such molecules increase GLP-1 receptor expression within the peri-portal region for restoring glucose homeostasis in every subject population outside of type-2 diabetes. Likewise, no screening assay is provided that would reliably identify molecules and subject population satisfying the claimed functional limitation and the claimed therapeutic outcome The disclosure therefore, provides insufficient guidance for practicing the full scope of the claims.
Working Examples
The specification contains one operative therapeutic example. The example utilizes dihydrotestosterone, a specific dose, a specific implant, a specific animal disease model, a specific anatomical location, a specific delivery technique, a specific imaging protocol, and specific metabolic endpoints. No experiments are provided for testosterone, DHEA, androstenedione, steroid analogs, non-steroidal compounds, peptides, biologics, and any other bioactive molecules and subject populations encompassed by the claims. Accordingly, the working examples support only a very small portion of the claimed genus.
Amount of experimentation required
To practice the full scope of the claims, one of ordinary skill would be required to identify additional candidate molecules and subject populations and determine, for each candidate whether the molecule upregulates GLP-1 receptor expression, produces sufficient receptor density, reaches the peri-portal region, remains locally active, avoids systemic toxicity, restores portal glucose sensing, improves insulin resistance, restores glucose homeostasis, and remains therapeutically effective following local administration. Such investigation would require extensive screening, animal experimentation, pharmacological optimization, dosing studies, imaging studies, receptor quantification, pharmacokinetics analysis, toxicology studies, and efficacy testing. Such experimentation constitutes research, rather than routine optimization.
Predictability of the art
The present field is highly unpredictable. Changes in molecular structure frequently produce substantial different biological activities. Likewise, compounds capable of increasing GLP-1 receptor expression in one tissue may fail to increase receptor expression in another tissue. Similarly, increased receptor expression does not necessarily restore glucose homeostasis. Consequently, one skilled in the art could not reasonably predict which member of the enormous claimed genus and which patient population would benefic from the therapeutic treatment.
Conclusion
Accordingly, the specification does not enable one of ordinary skill in the art to practice the full scope of the claimed invention without undue experimentation.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 15-27 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Independent claims 15 and 26 recite “providing at least one bioactive molecule upregulating the expression of GLP-1r.” This limitation is indefinite because one of ordinary skill in the art cannot determine with reasonably certainty whether a given molecule satisfies the claimed limitation. Specifically, the claims do not specify the amount of GLP-1r upregulation required, the tissue in which GLP-1r expression must be increase, the cell in which expression in measured, the assay used to determine expression, the reference or baseline against which expression is compared, and the time in which expression is evaluated. The specification discusses receptor density, receptor expression, receptor activity, PET imaging, molecular imaging, and various biological measurements without establishing an objective boundary for determining when a molecule constitutes a “bioactive molecule upregulating the expression of GLP-1r.” Accordingly, the metes and bounds of the claims cannot be determined with reasonably certainty.
Claims 15-27 recite “GLP-1r” without defining whether the recited limitation refers to receptor protein, receptor density, receptor expression, receptor activity, receptor signaling, receptor occupancy, or receptor function. The specification uses these terms interchangeably throughout the disclosure. Consequently, one skilled in the art would not reasonably be apprised of the scope of the invention.
Claim 18 recites several alternatives dose limitation connected by “preferably,” “more preferably,” and “yet more preferably.” According, it is unclear whether the claim encompasses a dose at least about 10-fold inferior, or about 100-fold inferior, or about 10-fold to about 100-fold inferior, or another alternative. Likewise., claim 19 and 20 recite multiple preferred embodiments rather than positively reciting the claimed subject matter. Accordingly, the metes and bounds cannot be determined with reasonable certainty.
Claims 20 and 27 recite “wherein it is administered at a dose that is equal or superior to a 100 µg/24 h for dihydrotestosterone….” The claims are indefinite because the dosage limitation is expressed relative to dihydrotestosterone, while the claims broadly encompass a “bioactive molecule.” The claims therefore fail to explain how one of ordinary skill would determine the corresponding dosage for bioactive molecules having different molecular weight, pharmacokinetic properties, receptor affinities, therapeutic indices, mechanism of action, or biological activities. Consequently, one skilled in the art cannot determine the scope of the dosage limitation for compounds other than dihydrotestosterone.
Claim 20 recites, in relevant part, “…. Wherein the bioactive molecule is dihydrotestosterone, and wherein it is administered at a dose….”. The pronoun “it” does not clearly identify its antecedent. In the context of the claim, “it” could reasonably refer to bioactive molecule, dihydrotestosteone, or the method itself. Accordingly, the scope of the claim is rendered unclear because it us uncertain which subject is required to be administered at the recited dose. Applicant may resolve the ambiguity by replacing the pronoun “it” with the intended antecedent, for example, “the bioactive molecule is administered” or “the dihydrotestosterone is administered” if that is the intended meaning.
Claim 23 recites “GLP-1r is detected” without specifying receptor expression, receptor density, receptor activity, receptor localization, receptor occupancy, or receptor function. Likewise, the claim fails to specify the analytical technique used to determine the claimed detection. Accordingly, the scope of the claim cannot be determined with reasonably certainty.
Claim 21 recites “a reduction of the density of GLP-1r … as compared to the density of GLP-1r in a healthy subject… “The claim is indefinite because the recited comparison relies upon a “healthy subject” without establishing an objective standard for such comparison. The claim does not define age, sex, BMI, metabolic status, glucose status, insulin sensitivity, imaging protocol, normal receptor density, or acceptable reference population. Because receptor densify may vary among healthy individuals, one of ordinary skill cannot determine with reasonable certainty whether a particular subject satisfies the claimed invention.
Claims 15 and 26 require “upregulating” without reciting a baseline against which the claimed increase is measured. The claims therefore fail to define whether the increased is measure relative to pretreatment levels, untreated controls, healthy controls, disease controls, vehicle controls, or another references. Accordingly, the functional limitation lacks objective boundaries and renders the scope of the claim uncertain.
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.
Claims 15-17, 19, 20, 23, 24, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Zhu et al. (Biomedicine & Pharmacotherapy 120 (2019) pages 1-12 in view of Malbert et al. (Diabetes, vol 70, no. 1, January 1, 2021, pages 99-110). Both cited in the IDS dated 04/03/2025 and 05/24/2024.
Zhu teaches that metformin can be used to upregulate GLP-1R that has been found to be downregulated by high glucose. Additionally, Zhu et al. teaches DHT (dihydrotestosterone) treatment can achieved similar result in type 2 diabetic and obese mice. So, therefore, DHT can be used to treat type 2 diabetes by upregulated GLP-1r which is known to be downregulated by high glucose of the type 2 and obese mice. (See Abstract.) Moreover, Zhu teaches DHT was injected subcutaneously 400 µg/body/day to the mice. (See first paragraph of the right column of page 2.)
Zhu does not teach the administration DHT at least partially in the wall of the portal
vein and/or connective tissue surrounding the portal vein. Additionally, Zhu does not teach the peri-portal region is accessed by direct laparoscopic access.
Malbert teaches the presence or detection of GLP-1R expression in the portal vein system and further teaches that GLP-1 receptor density by positron emission tomography (PET) using a GLP-1 receptor position-emitting ligand ([68Ga] Ga-DO3A-VS-Cys40-Exendin-4) together with computed tomography (CT) for anatomical localization. (See Abstract.)
It would have been obvious to one of ordinary skill in the art at the time the invasion was filed to administer the GLP-1r-upregulating bioactive molecule taught by Zhu locally to the peri-portal region using the laparoscopic portal access technique taught by Malbet as an alternative local administration technique to the subcutaneous administration taught by Zhu because Malbert demonstrates that laparoscopic placement of a catheter or implant permits precise delivery to the peri-portal region of the portal vein while simultaneously allowing localization and monitoring of GLP-1 receptor expression within the portal glucose sensor. One of ordinary skill in the art would have reasonably expected that substituting Malbert’s known local laparoscopic delivery technique for Zhu’s systemic subcutaneous administration would have predictably increase delivery of the GLP-1r-upregulating molecule directly to the intended peri-portal target tissue while reducing systemic exposure and associated off-target distribution. The substitution merely employs a known alternative route of administration to deliver the same therapeutic agent to the desired target and therefore represents the predictable use of prior-art elements according to their established functions.
With respect to claim 20, Zhu further teaches administering DHT at approximately 400 µg/body/day to diabetic mice. The claimed dose of 100 µg/24h to 1000 µg/24h encompasses Zhu’s disclosed daily dose. Malbert teaches locally admitting therapeutic agents to the peri-portal vein region using laparoscopic access. Therefore, it would have been obvious to administer Zhu’s known effective daily dose of DHT using Malbert’s localized peri-portal administration technique to deliver the therapeutic agent directly to target tissue while minimizing or reducing systemic exposure.
With respect to claim 23, Moreover, Malbert teaches that therapeutic strategies directed to the GLP-1 system are clinically useful for treating diabetes, but further teaches that patient exhibits substantial variability in therapeutic response. Malbert therefore recognizes the need for minimally invasive tools capable of identifying subject most likely to respond to GLP-1-based therapies in a personalized medicine approach. See third paragraph of the left column of page 108.) Accordingly, it would have been obvious to perform the known PET detection of peri-portal GLP-1r expression before administering Zhu’s GLP-1r-upregulating therapy in order to identify suitable subjects and guide treatment.
With respect to claim 24, Malbert teaches laparoscopic abdominal access was used to insert a silicon catheter with its distal end located precisely at the center of the 40-mm portal segment under scrutiny. (See first paragraph of the right column of page 101.) Malbert reports that obese insulin-resistant animals exhibit reduced GLP-1 receptor expression within the peri-portal glucose sensor relative to healthy animal and performs PET imaging to identify that reduction before therapeutic intervention. Malbert also teaches detecting a reduction in GLP-1 receptor density within the peri-portal region by comparing insulin-resistant obese animals with healthy lean animals. (See texts on page 102 bridging pages 103 and 104; and Figures 1-3.) So, Malbert teaches detecting a reduction in G:P-1 receptor density in comparison with a healthy subject prior to the subsequent experimental intervention.
Claims 18, 21, 26, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Zhu et al. (Biomedicine & Pharmacotherapy 120 (2019) pages 1-12 in view of Malbert et al. (Diabetes, vol 70, no. 1, January 1, 2021, pages 99-110) as applied to claims 15-17, 19, 23, 24, and 25 in further view of Corboy Jr. (US9,987,213 B2) and Choy et al. (Pharm Res. 2011 May; 28(5): 943–948).
The teachings of Zhu and Malbert with respect to the bioactive molecule upregulating GLP-1r and the local administration thereof to the peri-portal region of the portal vein have been discussed supra. Claims 18 and 26 further recite that the bioactive molecule is administered at a dose relative to the ED50 of the molecule, and claim 27 further limits the daily dose of dihydrotestosterone.
Zhu and Malbert do not expressly teach selecting the administered dose based upon a specific fraction of the ED50 of the bioactive molecule. Additionally, Zhu and Malbert do not expressly teach the bioactive molecule is administered in a volume that is equal or inferior to 1 mL per 24h period.
Corboy teaches a method for promoting or enhancing facial hair growth, comprising topically administering an effective amount of a pharmaceutically acceptable formulation of dihydrotestosterone to a target skin area, wherein the concentration of dihydrotestosterone in the dihydrotestosterone formulation is selected from the group consisting of (i) ranges from about 0.5% to about 25%, weight to weight, (ii) ranges from about 0.5% to about 25%, weight to volume, and (iii) ranges from about 0.5% to about 25%, volume to volume. (See claim 1.) Corboy also teaches effective amounts of the active compounds may be determined by one of ordinary skill in the art but will vary depending on the frequency of application and desired result, and bimatoprost will range from about 0.0000001 to about 10%, by weight, of the dermatological composition, preferably from about 0.001 to about 10%, by weight, of total dermatological composition, more preferably from about 0.03 to about 5%, by weight, of the composition and minoxidil will range from about 0.001 to about 10%, by weight, of the dermatological composition, preferably from about 0.01 to about 10%, by weight, of the composition. (See lines 11-20 of col. 14.) Corboy further teaches typically, the dose to be applied on the scalp is in the range of about 0.1 ng to about 100 mg per day, more preferably about 1 ng to about 10 mg per day, and most preferably about 10 ng to about 1 mg per day depending on the compound and the formulation. (See lines 18-22.)
Choy teaches local treatment of indications in the lung, eye or skin requires much lower doses than systemic delivery by mouth, which further expands the list of drug candidates for non-oral routes. On the other hand, systemic delivery of drugs via non-oral routes may be limited by the maximum dose that can be absorbed across their smaller surface area, especially for ocular and transdermal delivery, compared to the large surface area available via the oral route. (See first paragraph of page 4.)
Corboy teaches that selection of an effective daily dose of an active agent is a result-effective variable that depends upon particular compound, formulation, frequency of administration and desired therapeutic effect, and further teaches daily doses ranging from about 0.1 ng to about 100 mg per day (24h). Choy further teaches that localized administration generally requires substantially lower doses than systemic administration because the therapeutic agent is delivered directly to the target tissue while minimizing system exposure. One of of ordinary skill in the art would therefore have been motived to optimize the amount of Zhu’s dihydrotestosterone administered by the localized peri-portal delivery technique taught by Malbert, including selecting a dose representing a fraction of the systemic ED50, though routine experimentation in order to achieve the desired local therapeutic effect while minimizing systemic exposure and adverse effects. The optimization of a result-effective variable would have been well within the ordinary skill in the art.
With respect to claim 21, although Corboy does not expressly disclose administering the formulation in a volume equal or less than 1 mL per day, Corboy teaches that formulation parameters and dosage amounts are routinely optimized according to the active agent, formulation, and desired effect. Choy further teaches that localized administration requires substantially smaller amounts than system administration due to direct delivery to the target tissue. Accordingly, it would have been obvious to one of ordinary skill in the art to optimize the administered formulation volume, including selecting a volume of 1 mL, or less for localized peri-portal administration, since the volume of local delivered formulation constitutes a result-effective variable that would have been optimized through routine experimentation to achieve the effective local delivery while minimizing leakage and systemic exposure.
Conclusion
Claims 15-27 are not allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEAN P CORNET whose telephone number is (571)270-7669. The examiner can normally be reached Monday-Thursday from 7.00am-5.30pm.
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, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JEAN P CORNET/Primary Examiner, Art Unit 1628
Prosecution Insights