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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/30/2026 has been entered.
Summary
Receipt of Applicant’s Amendment and Remarks filed March 30, 2026 in response to the Final Office Action dated December 29, 2025 is acknowledged.
Claims 1-11 were pending.
Claims 1, 6, 8, and 11 are currently amended.
Claims 9,13-20 are cancelled.
Claims 12 is withdrawn from consideration.
Claims 21 and 22 are new.
Claims 1-8, 10-11, 21, and 22 are pending and including in examination is this application.
Election/Restrictions
Applicant elected claims 1-11 without traverse in response filed 7/14/2025.
Claims 12-20 are all withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. The restriction was made Final.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/30/2026 is in compliance with the provisions of 37 CFR 1.98. Accordingly, the information disclosure statements has been considered by the examiner. Signed copies have been attached to this office action.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-8, 10-11, 21, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Lowenthal (US 2019/0269780 A1) in view of Becker (Emergency Drug kits: Pharmacological and Technical Considerations).
Scope and Content of the Prior Art
Lowenthal discloses pharmaceutical formulations comprising epinephrine for treating anaphylaxis by nasal, inhalation, or pulmonary delivery, wherein the formulations comprise one or more absorption-enhancing adjuvants that improve systemic bioavailability of the active agent (Abstract; ¶¶0004–0010). Critically, Lowenthal benchmarks its nasal formulations against intramuscular (IM) injection, explicitly disclosing that formulations comprising absorption enhancers provide IM-injection-like pharmacokinetics, or subcutaneous (SC)-like absorption, or pharmacokinetics in between (¶0018). Lowenthal further discloses IM and SC as routes of administration directly (¶¶0007–0008), and teaches that IM injection in the lateral thigh is the clinically optimal method for epinephrine bioavailability given the high vascularity of leg muscle (¶0084). Lowenthal therefore does not restrict its teachings to intranasal administration; rather, it identifies IM and SC injection as the clinical benchmark and target pharmacokinetic standard.
Lowenthal further discloses that its formulations may comprise excipients selected from tonicity agents, stabilizing agents, buffers, pH adjustment agents, and absorption-enhancing adjuvants in combination (¶0027). Tonicity agents include magnesium chloride (MgCl2) (¶¶0387, 0412). Absorption-enhancing adjuvants include a broad list of compounds at ¶¶0107–0168 encompassing vasodilatory agents, modulators of epithelial junction physiology, and selective transport-enhancing agents. Lowenthal’s formulations thus combine a tonicity agent component (which may be MgCl2) with an absorption-enhancing adjuvant component in the same formulation.
Becker discloses that epinephrine and atropine are standard drugs administered intramuscularly in basic emergency drug kits (page 171, right column; page 172; page 175). Becker confirms IM injection as the clinically established parenteral route for these ER-APIs in emergency rescue settings.
Differences Between the Prior Art and the Claims; Motivation to Combine
Regarding claims 1 and 4, Lowenthal teaches a formulation comprising epinephrine (ER-API) and absorption-enhancing adjuvants, wherein the formulation achieves IM-injection-like pharmacokinetics (¶0018). Lowenthal discloses MgCl2 as a tonicity agent component of the same formulations (¶¶0387, 0412). Becker confirms IM administration of epinephrine is clinically established for emergency rescue (page 172).
It would have been prima facie obvious to one of ordinary skill in the art (PHOSITA) to adapt the absorption-enhancer-containing formulations of Lowenthal to parenteral (IM or SC) administration. The motivation is supplied by Lowenthal itself: Lowenthal identifies IM injection as the pharmacokinetic benchmark its nasal formulation is designed to replicate (¶¶0018, 0084), and discloses IM and SC as direct routes of epinephrine administration (¶¶0007–0008). Becker reinforces that IM is the established clinical route for epinephrine in emergency settings. Applying Lowenthal’s adjuvant technology to a direct IM formulation to further optimize systemic absorption is straightforward optimization by a PHOSITA.
It would further have been obvious to select MgCl2 as the absorption-enhancing adjuvant. Lowenthal already includes MgCl2 in its formulations as a tonicity agent alongside absorption-enhancing adjuvants (¶¶0027, 0387, 0412). Importantly, magnesium is well-established in the pharmacological and physiological arts as a vasodilatory agent — it relaxes vascular smooth muscle and increases local blood flow and tissue perfusion at an injection site. Vasodilatory agents are expressly included among Lowenthal’s absorption-enhancing adjuvant categories (¶¶0107–0168). A PHOSITA formulating a parenteral composition from Lowenthal’s disclosed excipient set would have had clear reason to evaluate MgCl2 — an excipient already present in Lowenthal’s formulations — for its vasodilatory absorption-enhancing potential at an IM or SC injection site. Where there is a design need (enhanced IM/SC absorption), a finite and identified pool of candidate excipients (Lowenthal’s disclosed list), and a reasonable expectation of success (known vasodilatory biology of MgCl2), the selection is obvious. Even if the precise mechanism by which MgCl2 enhances parenteral absorption were not predicted in advance, KSR does not require mechanism prediction — it requires only reason to select and a reasonable expectation of success. A PHOSITA presented with a finite list of excipients already present in analogous formulations would be motivated to evaluate each candidate systematically, and MgCl2 — already present in Lowenthal’s formulations alongside absorption enhancers — would be an obvious candidate to evaluate. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007).
The claimed concentration range of about 0.3% to about 3% (w/v) represents routine optimization. Determination of effective concentrations for a known excipient in a parenteral formulation is within ordinary skill in the art. In re Aller, 220 F.2d 454, 456 (CCPA 1955).
Regarding claim 5, Lowenthal does not specifically teach atropine as the ER-API. Becker discloses that atropine is administered intramuscularly in emergency drug kits for management of bradycardia and hypotension (page 175). It would have been obvious to a PHOSITA to incorporate atropine as the ER-API in Lowenthal’s absorption-enhancer-containing formulation, motivated by Becker’s teaching that atropine is a known IM emergency drug and by the same rationale applied to epinephrine above.
Regarding claims 2, 3, and 10, Lowenthal teaches that absorption enhancers increase the rate at which epinephrine is absorbed into the circulatory system and provide improved pharmacokinetic outcomes including increased Cmax, reduced Tmax, and improved dose proportionality compared to formulations without absorption enhancers (¶0479). The limitations directed to promoting systemic absorption rate upon injection (claim 2), shorter time to onset upon IM/SC injection (claim 3), and increasing systemic absorption rate upon IM/SC injection (claim 10) are thus taught by Lowenthal’s absorption enhancer functionality.
Regarding claim 6, Lowenthal discloses comparative bioavailability data for IM epinephrine in Tables 5–9c (¶¶0550–0583), wherein Tmax for IM injection in the lateral thigh ranged from 4 to 6 minutes for the first 5 readings (Table 9b). A time to onset of about 5 minutes or less overlaps with and is taught by Lowenthal’s IM injection onset data.
Regarding claims 7 and 8, Lowenthal discloses that mean time to maximum plasma concentration (Tmax) for IM injection of epinephrine is 61 minutes (Table 7; ¶¶0550–0583). Mean Tmax of about 2.0 hours or less (claim 7) and about 0.75 hour or less (claim 8) both encompass this IM injection Tmax value taught by Lowenthal.
Regarding claim 11, the claim recites that the adjuvant is present in the parenteral formulation from about 0.5% to about 1.5% (w/v). Lowenthal discloses that in certain embodiments the absorption-enhancing adjuvant is present in a range from 0.005% to about 0.5% (¶0415), placing the upper boundary of Lowenthal’s disclosed range at the lower boundary of the claimed range. It would have been obvious to a PHOSITA to optimize the adjuvant concentration beyond Lowenthal’s disclosed ceiling. Lowenthal expressly teaches that higher absorption enhancer concentration provides improved pharmacokinetic outcomes including increased Cmax and improved dose proportionality (¶0479). That teaching itself provides a PHOSITA with reason to explore concentrations above Lowenthal’s disclosed range to further improve absorption — a straightforward upward optimization from a known starting point. Where a reference teaches a range and also teaches that higher values within and proximate to that range yield improved results, experimentation to identify an optimal concentration above the disclosed ceiling involves only routine optimization with a reasonable expectation of success. In re Aller, 220 F.2d 454, 456 (CCPA 1955) (optimization of conditions within and proximate to a disclosed range is within ordinary skill in the art).
Regarding claims 21 and 22, the claims recite the adjuvant at about 1% and about 2% (w/v) respectively. These concentrations fall within the claimed range of independent claim 1 (0.3–3% w/v) and represent specific points within the concentration space taught and rendered obvious by Lowenthal. Selection of specific concentrations within a range taught or suggested by the prior art is prima facie obvious. In re Aller, 220 F.2d 454, 456 (CCPA 1955).
Response to Arguments
Applicant’s arguments filed March 30, 2026 have been fully considered but are not persuasive for the following reasons.
Argument 1: Lowenthal teaches away from parenteral administration. This argument is not persuasive. A reference “teaches away” only when it criticizes, discredits, or otherwise discourages the claimed solution. In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004). Lowenthal does neither. Lowenthal expressly discloses IM and SC as routes of epinephrine administration (¶¶0007–0008), identifies IM injection as the clinical optimum for epinephrine bioavailability (¶0084), and sets IM pharmacokinetics as the performance benchmark for its nasal formulations (¶0018). Far from discouraging parenteral administration, Lowenthal treats IM injection as the gold standard against which its intranasal formulations are measured. Applicant’s argument that absorption mechanisms are “fundamentally different” between nasal and parenteral routes does not establish that a PHOSITA would be discouraged from applying Lowenthal’s adjuvant technology to a parenteral context. The relevant mechanism for parenteral absorption — local vasodilation and enhanced tissue perfusion at the injection depot — is well within the scope of vasodilatory agents disclosed by Lowenthal (¶¶0107–0168), and MgCl2’s known vasodilatory biology makes it a rational candidate for IM/SC absorption enhancement regardless of its nasal mucosal mechanism. In any event, KSR does not require that a PHOSITA predict the precise mechanism of action before being motivated to combine known elements — the motivation to combine and reasonable expectation of success are established by Lowenthal’s own absorption-enhancer teachings and the known clinical utility of IM administration, independent of any mechanistic prediction.
Argument 2: MgCl2 is not recognized as an absorption enhancer in Lowenthal. Applicant is correct that Lowenthal lists MgCl2 as a tonicity agent, not an absorption enhancer. However, the rejection does not require that Lowenthal itself characterize MgCl2 as an absorption enhancer. Under KSR, obviousness does not depend on the prior art explicitly labeling a compound with the claimed function — it is sufficient that a PHOSITA would have had reason to select the compound and a reasonable expectation that it would achieve the claimed result. Lowenthal (1) already includes MgCl2 in its formulations; (2) discloses vasodilatory agents as a category of absorption-enhancing adjuvants (¶¶0107–0168); and (3) provides a finite excipient list from which selection of MgCl2 for its vasodilatory properties constitutes obvious experimentation. KSR, 550 U.S. at 421. Notably, Applicant cancelled claim 9 — which specifically recited an adjuvant selected from the ¶¶0107–0168 list — in this response, consistent with the Examiner’s position that MgCl2 is drawn from Lowenthal’s disclosed excipient universe.
Argument 3: Unexpected results. Applicant’s comparative pharmacokinetic data (Tables 2 and 4 of the specification) does not establish unexpected results over the closest prior art. MPEP 716.02(b) requires that comparative data be made against the closest prior art comparator — i.e., a parenteral formulation comprising a representative absorption-enhancing adjuvant from Lowenthal’s disclosed list other than MgCl2. Applicant’s data compares MgCl2-containing formulations against a plain parenteral formulation with no adjuvant. This comparison establishes only that an adjuvant improves absorption over no adjuvant — precisely the outcome Lowenthal predicts. It does not establish that MgCl2 produces results unexpectedly superior to other adjuvants from Lowenthal’s teaching. In re Baxter Travenol Labs, 952 F.2d 388, 392 (Fed. Cir. 1991).
Additionally, the data exhibits non-monotonic behavior that undermines a showing of unexpectedly superior results across the full claimed range (0.3–3% w/v). For epinephrine, 1% MgCl2 achieved a higher AUC2 than 2% MgCl2 (6.80 vs. 6.58 hr·ng/ml). For atropine, the 2% MgCl2 formulation “maintained within 10% of the control” for Cmax — a result that is not meaningfully superior to the control. This variability across the claimed concentration range further undermines a demonstration of unexpectedly superior results coextensive with the full scope of the claims. In re Harris, 409 F.3d 1339, 1344 (Fed. Cir. 2005) (unexpected results must be commensurate in scope with the claims).
Conclusion
Claims 1–8, 10–11, 21, and 22 remain rejected under 35 U.S.C. § 103.No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDRE MACH whose telephone number is (571)272-2755. The examiner can normally be reached 0800 - 1700 M-F.
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, Robert A Wax can be reached at 571-272-0323. 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.
/ANDRE MACH/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
Prosecution Insights