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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 8/21/25 has been entered.
Election/Restrictions and Claim Status
Applicants’ amendments and arguments filed 8/21/25 are acknowledged. Any objection or rejection from the 5/21/25 office action that is not addressed below is withdrawn based on the amendments.
37 CFR 1.121(c)(4)(i) state that the changes being made in a claim amendment are not shown when a claim is being canceled. Although claim 2 shows the changes being made, claim 2 is treated as a canceled claim and the claim amendment has been entered.
Previously, Group 1 was elected.
Claims 14-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 traverse in the reply filed on 11/11/24.
Claims 2 and 6 have been canceled.
Claims 1, 3-5, 7-13 and 22-23 are being examined.
Priority
The priority information is found in the filing receipt dated 10/28/24.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/27/25 has been considered by the examiner.
Claim Rejections - 35 USC § 103
Claims were previously rejected under 103 based on the reference cited below. Since the claims have been amended the rejection is updated to correspond to the instant claims.
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.
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, 3-5, 7-13 and 22-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Quay et al. (US 2008/0318837; ‘Quay’; first cited 1/30/25).
Quay teach glucose-regulating peptides including exenatide (sections 0001 and 0050-0051). Quay teach that exendin-4 is also known as exenatide (section 0051). Quay teach advantages of mucosal administration including convenience and speed of delivery as well reducing or eliminating compliance problems and side effects (section 0004). Quay teach compositions for transmucosal delivery for treating various ailments (section 0012). Quay teach varying the concentration of exenatide and recites concentrations from 0.5 mg/ml (section 0339). Quay teach that the effective dose can vary (section 0019). In Table 42, Quay teach examples with 0.04 mg/ml, 0.2 mg/ml and 0.4 mg/ml exendin-4. Quay specifically refers to a dose of 0.1-100 ug/kg (section 0019). In table 43 (page 49), Quay shows that exendin-4 at a dose level of 2 ug/kg is 0.04 mg/ml (40 ug/ml) and a dose level of 10 ug/kg is 0.2 mg/ml (200 ug/ml) and a dose level of 20 ug/kg is 0.4 mg/ml (400 ug/ml). Quay teach the use of salts of the peptides (section 0054). Quay teach that the compositions are often administered in an aqueous solution as a nasal or pulmonary spray and may be dispensed in spray form and systems for dispensing and containers and nebulizers are known in the art (section 0193). Quay teach kits and packages (section 0212) and provides details about spray devices (sections 0212-0223). Quay teach the use of a buffer for enhanced delivery (sections 0083-0087) and recites acetate buffer (section 0086) specifically sodium acetate (section 0201). Quay teach that the acetate buffer provided increased physical stability as well as a pH range of 4.7-5.5 (section 0336). Quay teach mannitol as an isotonizing agent (section 0197). Quay expressly teach a range of mannitol of 50-200 mM (Table 28 on page 43). Quay teach optimal osmolarity includes 200 mOsm (section 0336). Quay teach that removal of components of the composition could lead to greater ease in approval by the FDA and decreases the time for manufacturing and reduces the cost of goods (section 0340). Quay specifically teach preservative-free formulations (section 0341 and Tables 40-41). Quay teach numerous examples. Quay teach formulations for intranasal dosing that include 0.2 mg/ml exendin-4, 10 mg/ml EDTA, 10 mM arginine buffer at pH 4 (Table 42 formulation Group 4). Quay teach transmucosal exenatide formulations that comprise exenatide, 20 mM citrate buffer at pH 4.5 and 40 or 80 mM mannitol (Table 29 first 2 formulations). Quay teach a transmucosal exenatide formulations that comprise exedin-4, NaCl and 30 mM acetate buffer at pH 5.25 (‘OEF + arg, 30 Acetate’ of Table 33) or 10 mM acetate buffer at pH 5.25 or 5.5 (‘OEF + arg’ and ‘OEF’ of Table 33). Quay teach stability of formulations (section 0335).
Quay does not teach a specific example that reads on claim 10 for example.
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Quay based on the specific teachings and suggestions of Quay. Quay teach numerous examples of exenatide compositions (Tables 29, 33 and 42). Quay teach varying the concentration of exenatide and recites concentrations from 0.5 mg/ml (section 0339). Quay teach that the effective dose can vary (section 0019). In Table 42, Quay teach examples with 0.04 mg/ml, 0.2 mg/ml and 0.4 mg/ml exendin-4. Thus, one would have been motivated to optimize the amount of exenatide (see MPEP 2144.05 II A). Since Quay teach the use of salts of the peptides (section 0054) one would have been motivated to do such. Quay teach the use of a buffer for enhanced delivery (sections 0083-0087) and recites acetate buffer (section 0086) specifically sodium acetate (section 0201). Quay teach that the acetate buffer provided increased physical stability as well as a pH range of 4.7-5.5 (section 0336). Quay teach examples with 30 mM acetate buffer at pH 5.25 (‘OEF + arg, 30 Acetate’ of Table 33) or 10 mM acetate buffer at pH 5.25 or 5.5 (‘OEF + arg’ and ‘OEF’ of Table 33). Thus, one would have been motivated to use the sodium acetate buffer based on the advantageous effects. Since Quay teach that the compositions are often administered in an aqueous solution as a nasal or pulmonary spray and may be dispensed in spray form and systems for dispensing and containers and nebulizers are known in the art (section 0193) and teach kits and packages (section 0212) and provides details about spray devices (sections 0212-0223) one would have been motivated to package and prepare in such forms. Quay specifically recognizes administration to humans (sections 0001, 0011 and 0021). Quay teach mannitol as an isotonizing agent (section 0197) and teach a range of mannitol of 50-200 mM (Table 28 on page 43) and teach transmucosal exenatide formulations that comprise 40 or 80 mM mannitol (Table 29 first 2 formulations) so one would have been motivated to use such components and conditions. Quay teach that removal of components of the composition could lead to greater ease in approval by the FDA and decreases the time for manufacturing and reduces the cost of goods (section 0340) and specifically teach preservative-free formulations (section 0341 and Tables 40-41). Thus one would have been motivated to make preservative free compositions. One would have had a reasonable expectation of success since the components and their functions and methods of combining were known.
In relation to the exenatide recited in claims 1 and 10, Quay teach formulations for intranasal dosing that include 0.2 mg/ml exendin-4 (Table 42 formulation Group 4). Quay teach that exendin-4 is also known as exenatide (section 0051). Quay teach varying the concentration of exenatide and recites concentrations from 0.5 mg/ml (section 0339). Quay teach that the effective dose can vary (section 0019). In Table 42, Quay teach examples with 0.04 mg/ml, 0.2 mg/ml and 0.4 mg/ml exendin-4. Quay specifically refers to a dose of 0.1-100 ug/kg (section 0019). In table 43 (page 49), Quay shows that exendin-4 at a dose level of 2 ug/kg is 0.04 mg/ml (40 ug/ml) and a dose level of 10 ug/kg is 0.2 mg/ml (200 ug/ml) and a dose level of 20 ug/kg is 0.4 mg/ml (400 ug/ml) showing that doses of 0.1-100 ug/kg (section 0019) overlaps with the claimed range. In addition, one would have been motivated to optimize the amount of exenatide (see MPEP 2144.05 II A).
In relation to the buffer of claims 1, 3-5 and 10, Quay teach a transmucosal exenatide formulations that comprise 30 mM acetate buffer at pH 5.25 (‘OEF + arg, 30 Acetate’ of Table 33) or 10 mM acetate buffer at pH 5.25 or 5.5 (‘OEF + arg’ and ‘OEF’ of Table 33). Quay teach the use of a buffer for enhanced delivery (sections 0083-0087) and recites acetate buffer (section 0086) specifically sodium acetate (section 0201). Quay teach that the acetate buffer provided increased physical stability as well as a pH range of 4.7-5.5 (section 0336).
In relation to the osmolarity and mannitol of claims 1, 7-8, 10 and 22-23, Quay teach transmucosal exenatide formulations that comprise 40 or 80 mM mannitol (Table 29 first 2 formulations). Quay teach mannitol as an isotonizing agent (section 0197). Quay expressly teach a range of mannitol of 50-200 mM (Table 28 on page 43) as in claim 8. MPEP 2144.05 I recognizes that where the claimed range overlaps or lies inside ranges disclosed by the prior art a prima facie case of obviousness exists. Quay teach optimal osmolarity includes 200 mOsm (section 0336). In relation to claim 9, Quay teach a formulation (Table 42 formulation Group 4) that does not contain a surfactant or stabilizer. Quay teach that removal of components of the composition could lead to greater ease in approval by the FDA and decreases the time for manufacturing and reduces the cost of goods (section 0340) and specifically teach preservative-free formulations (section 0341 and Tables 40-41). Thus one would have been motivated to make preservative free compositions.
In relation to the packaging of claims 1 and 11, claims 1 and 11 both recite ‘for administration’ which is an intended use. Quay teach formulations for intranasal dosing (Table 42 formulation Group 4) so the formulations would be prepared and suitable for intranasal dosing. Further, Quay teach that the compositions are often administered in an aqueous solution as a nasal or pulmonary spray and may be dispensed in spray form and systems for dispensing and containers and nebulizers are known in the art (section 0193) and teach kits and packages (section 0212) and provides details about spray devices (sections 0212-0223) so one would have been motivated to package and prepare in such forms. Quay specifically recognizes administration to humans (sections 0001, 0011 and 0021) and packaging for humans or other mammals would not necessarily differ.
In relation to claim 12, Quay teach the use of salts of the peptides (section 0054). Quay specifically recites acetate (sections 0086 and 0201).
In relation to claim 13, the composition of Quay (Table 42 formulation Group 4) teach components as claimed so it is interpreted as having the function as claimed absent evidence to the contrary. Quay teach stability of formulations (section 0335).
Response to Arguments - 103
Applicant's arguments filed 8/21/25 have been fully considered but they are not persuasive with respect to the rejection set forth above.
Although applicants argue that the claims have been amended, the amended claims are addressed above.
Although applicants argue about the osmolarity, Quay teach mannitol as an isotonizing agent (section 0197). Quay expressly teach a range of mannitol of 50-200 mM (Table 28 on page 43) as in instant claim 8 for example. Applicants own specification (section 0033 and Table 4) recognizes that mannitol is used to adjust the osmolarity. Osmolarity is measured on a volume basis (for example per L) and osmolality is measured on a mass basis (for example per kg). Claim 1 recites an aqueous buffer and water has a known density so the osmolarity and osmolality are very similar in value.
Although applicants argue that the specification demonstrates the effectiveness of a composition with an osmolarity within the claimed range versus the ineffectiveness of a composition with an osmolarity higher than the claimed range, section 0082 of the specification refers to the presence of phenolic preservatives as being the difference and refers to the phenolic preservative as being low performing. The inclusion of a low performing preservative is not necessarily the equivalent of showing a criticality of a range. Quay teach that removal of components of the composition could lead to greater ease in approval by the FDA and decreases the time for manufacturing and reduces the cost of goods (section 0340) and specifically teach preservative-free formulations (section 0341 and Tables 40-41). MPEP 716.02(d) refers to demonstrating criticality of a claimed range and refers to comparing a sufficient number of tests both inside and outside the claimed range and MPEP 716.02(b) states that the burden is on the applicant to establish unexpected results. There are inadequate facts to conclude unexpected results.
Although applicants argue about the specific amount of exenatide, Quay specifically refers to a dose of 0.1-100 ug/kg (section 0019). In table 43 (page 49), Quay shows that exendin-4 at a dose level of 2 ug/kg is 0.04 mg/ml (40 ug/ml) and a dose level of 10 ug/kg is 0.2 mg/ml (200 ug/ml) and a dose level of 20 ug/kg is 0.4 mg/ml (400 ug/ml) showing that doses of 0.1-100 ug/kg (section 0019) overlaps with the claimed range. MPEP 2144.05 expressly recognizes that in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. MPEP 2144.05 II A recognizes that generally differences in concentration will not support the patentability of the subject matter encompassed by the prior art.
Although applicants argue that claims refer to packaging for humans via inhalation, Quay teach formulations for intranasal dosing (Table 42 formulation Group 4) so the formulations would be prepared and suitable for intranasal dosing. Quay specifically recognizes administration to humans (sections 0001, 0011 and 0021) and packaging for humans or other mammals would not necessarily differ. Further, Quay teach that the compositions are often administered in an aqueous solution as a nasal or pulmonary spray and may be dispensed in spray form and systems for dispensing and containers and nebulizers are known in the art (section 0193) and teach kits and packages (section 0212) and provides details about spray devices (sections 0212-0223) so one would have been motivated to package and prepare in such forms.
Although applicants argue about claim 13, Quay (Table 42 formulation Group 4) teach components as claimed so it is interpreted as having the function as claimed absent evidence to the contrary. Quay teach stability of formulations (section 0335). NPL document 6 of the 8/27/25 IDS recognizes that the examples in the description of the present application do not prove that low osmotic pressure and the absence of phenolic preservatives makes exenatide more stable (page 2 last paragraph).
Although applicants argue about claim 23, Quay specifically refers to a dose of 0.1-100 ug/kg (section 0019). In table 43 (page 49), Quay shows that exendin-4 at a dose level of 2 ug/kg is 0.04 mg/ml (40 ug/ml) and a dose level of 10 ug/kg is 0.2 mg/ml (200 ug/ml) and a dose level of 20 ug/kg is 0.4 mg/ml (400 ug/ml) showing that dose of 0.1-100 ug/kg (section 0019) overlaps with the claimed range. MPEP 2144.05 expressly recognizes that in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. MPEP 2144.05 II A recognizes that generally differences in concentration will not support the patentability of the subject matter encompassed by the prior art.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 RONALD T NIEBAUER whose telephone number is (571)270-3059. The examiner can normally be reached M - F 6:30 - 2:30 EST.
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, Melissa Fisher can be reached at 571-270-7430. 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.
RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658