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 .
Summary
Receipt of Applicant’s Amendment and Remarks filed July 29, 2026 is acknowledged.
Claims 1-8, 10-11, 21, and 22 are pending
Claim 1 is amended.
Claims 9 and 13-20 remain cancelled.
Claims 12 is withdrawn from consideration.
Claims 1-8, 10-11, 21, and 22 are pending and including in examination is this application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/31/2026 and 03/30/2026 are 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.
Maintained Rejections
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 amended claimed concentration range of about 0.5% 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 July 29, 2026 have been fully considered but are not persuasive.
As an initial matter, amended claim 1 now recites an adjuvant concentration of about 0.5% (w/v) to about 3% (w/v), replacing the previous floor of about 0.2% (w/v). This amendment does not overcome the rejection or necessitate any new ground. The amended floor of claim 1 now matches the floor already rejected in claim 11 (about 0.5% to about 1.5% (w/v)), which was rejected using Lowenthal’s disclosed adjuvant concentration ceiling of about 0.5% (¶ 0415) together with Lowenthal’s teaching that higher adjuvant concentrations yield improved pharmacokinetic outcomes, including increased Cmax and improved dose proportionality (¶ 0479). That same rationale — routine optimization above a disclosed ceiling where the reference itself teaches that higher values in that direction improve the relevant result — applies with equal force to amended claim 1. See In re Aller, 220 F.2d 454, 456 (CCPA 1955). No new reference or new rationale is required to reach the amended claim.
Argument 1: (Lowenthal does not motivate MgCl2 as an absorption enhancer in the claimed range): This argument was raised and addressed in the prior Office action (Argument 2 therein) and is not persuasive for the same reasons. Applicant is correct that Lowenthal categorizes MgCl2 as a tonicity agent rather than as a member of its absorption-enhancer list (¶¶ 0107–0168). However, obviousness does not require the prior art to label a compound with the claimed function. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007). MgCl2 is already present in Lowenthal’s formulations (¶¶ 0027, 0387, 0412) alongside disclosed absorption enhancers, and magnesium’s vasodilatory pharmacology — a mechanism expressly within Lowenthal’s absorption-enhancer categories (¶¶ 0107–0168) — supplies a PHOSITA with reason to evaluate it for that function and a reasonable expectation of success independent of Lowenthal’s own labeling.
Applicant’s newly-cited authority does not change this result. In re Kubin, 561 F.3d 1351, 1359 (Fed. Cir. 2009) and In re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988) hold that “obvious to try” is improper only where the prior art gives no indication which parameters are critical or which of many choices is likely to succeed. That is not this case: Lowenthal identifies a finite, already-formulated excipient set (¶¶ 0027, 0387, 0412) rather than an unbounded field of candidates, and MgCl2’s vasodilatory mechanism is well-established in the pharmacological art independent of Lowenthal. For the same reason, Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1359 (Fed. Cir. 2007) is distinguishable. In Takeda, the prior art disclosed a broad, undifferentiated genus of compounds with no reason to select the particular claimed compound. Here, MgCl2 is not merely one member of an undifferentiated genus — it is already a formulated component of Lowenthal’s compositions (¶¶ 0027, 0387, 0412), positioned alongside a functionally-defined absorption-enhancer category (vasodilatory agents, ¶¶ 0107–0168) that its own known pharmacology satisfies. This is materially narrower than the unstructured genus at issue in Takeda.
Argument 2 (no result-effective variable / Antonie): Applicant argues that because Lowenthal does not recognize MgCl2 as having absorption-enhancing properties, MgCl2 cannot be treated as a result-effective variable under In re Antonie, 559 F.2d 618 (CCPA 1977), and the claimed concentration range cannot be routine optimization. This is not persuasive for two independent reasons. First, as discussed above, recognition of the variable’s effect on the result — not the reference’s own characterization of the compound — is what triggers the RFV analysis, and Lowenthal’s own data (¶ 0479) ties adjuvant concentration generally to absorption-related pharmacokinetic outcomes (Cmax, Tmax, dose proportionality), which is sufficient to establish concentration as a result-effective variable a PHOSITA would optimize once MgCl2 is selected as the adjuvant for the reasons given above. Second, and independently, this is the same variable and the same evidentiary basis (¶¶ 0415, 0479) already applied without dispute to claim 11’s overlapping range; Applicant has not identified any basis to treat the now-amended claim 1 range differently.
Argument 3 (hindsight / McLaughlin): This argument is not persuasive. As explained above, the motivation to select MgCl2 and to optimize its concentration derives entirely from Lowenthal’s own disclosure — its inclusion of MgCl2 in the formulation (¶¶0027, 0387, 0412), its absorption-enhancer category definitions (¶¶ 0107–0168), and its concentration-outcome teaching (¶ 0479) — together with MgCl2’s independently known vasodilatory pharmacology. None of this reasoning is drawn from or reconstructed using Applicant’s own disclosure. In re McLaughlin, 443 F.2d 1392, 1395 (CCPA 1971).
Argument 4 (Becker does not cure Lowenthal): Becker is relied upon solely for its teaching that epinephrine and atropine are administered intramuscularly in emergency drug kits, confirming IM as the established clinical route for these ER-APIs; it is not relied upon for the absorption-enhancer or MgCl2 teachings, which are supplied by Lowenthal alone. Applicant’s argument does not address the combination as actually applied.
For the foregoing reasons, the rejection of claims 1–8, 10–11, 21, and 22 under 35 U.S.C. § 103 is maintained. This Office Action is made FINAL because the amendment to claim 1 does not necessitate a new ground of rejection — the amended limitation is fully addressed by the art and rationale already of record. See MPEP § 706.07(a).
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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.
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/ANDRE MACH/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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