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 . 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.
Priority
The instant application claims foreign priority to PCT/CN2021/142542 filed on 12/29/2021. The certified copy of the foreign priority application filed in the instant application is acknowledged.
Status of the Claims
The claim amendments and remarks filed on 07/17/2025 is acknowledged. Claims 1, 21-23, 30, 32, 37-38 are amended. Claims 2-20, 24-29, 33-36, and 39-47 are cancelled. Claims 48-58 are newly added.
Claims 1, 21-23, 30-32, 37-38, and 48-58 are pending.
Claims 37-38 were previously withdrawn in the office action dated 01/21/2025 as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Newly added claims 48-58 are drawn to elected Group I of a pharmaceutical composition.
Accordingly, claims 1, 21-23, 30-32, and 48-58 are being examined on the merits herein.
Withdrawn Rejections
35 USC 112(b) rejection for claims 7, 10, and 23 are withdrawn in view of claims 7 and 10 being cancelled and claim 23 being to amended to recite the weight ratio of (b) is about 1:2.
35 USC 102 rejection over Vegge et al. for claims 1-3, 5-7, 10, 14, 18, 21-22, 26, and 30-32 are withdrawn in view of claims 2-3, 5-7, 10, 14, 18, and 25 being cancelled, and claim 1 being amended to now include an incretin; (b) capric acid; (c) 8-(2-hydroxybenzamido)octanoic acid; and wherein the weight ratio of (b) to (c) ranges from about 1:2 to 1:5, which has narrowed the scope of the claims.
35 USC 102 rejection over Pedersen et al. for claims 1-7. 10, 14, 21, 26, and 30-32 are withdrawn in view of claims 2-7, 10, 14, and 26 being cancelled, and claim 1 being amended to now include an incretin; (b) capric acid; (c) 8-(2-hydroxybenzamido)octanoic acid; and wherein the weight ratio of (b) to (c) ranges from about 1:2 to 1:5, which has narrowed the scope of the claims.
35 USC 103 rejection over Vegge et al. for claims 4 and 23 as well as further in view of Kidron et al. for claim 19 are withdrawn in view of claims 4 and 19 being cancelled, and claim 1 being amended to now include an incretin; (b) capric acid; (c) 8-(2-hydroxybenzamido)octanoic acid; and wherein the weight ratio of (b) to (c) ranges from about 1:2 to 1:5, which has narrowed the scope of the claims.
35 USC 103 rejection over Pedersen et al. for claim 23 as well as further in view of Vegge et al. for claims 18 and 22 and further in view of Kidron et al. for claim 19 are withdrawn in view of claims 18-19 being cancelled, and claim 1 being amended to now include an incretin; (b) capric acid; (c) 8-(2-hydroxybenzamido)octanoic acid; and wherein the weight ratio of (b) to (c) ranges from about 1:2 to 1:5, which has narrowed the scope of the claims.
New Rejections Necessitated by the Amendments filed on 07/17/2025
Claim Rejections - 35 USC § 112
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 1, 21-23, 30-32, 37-38, and 48-56 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.
Claim 1 recites “… (a) an SGLT-2 inhibitor and an incretin; (b) capric acid or a pharmaceutically acceptable salt thereof; (c) 8-(2-hydroxybenzamido)octanoic acid or a pharmaceutically acceptable salt thereof, wherein the weight ratio of (b) to (c) ranges from about 1:2 to 1:5.”.
Here, claim 1 is indefinite because there is no conjunction such as “and” or “or” between (b) and (c) components, making it unclear if the (a), (b), and (c) components are all required or alternatives.
Claims 21-23, 30-32, 37-38, and 48-56 depend from claim 1, but do not overcome the described indefinite issue.
For purposes of examination, claim 1 is being interpreted as components (a), (b), and (c) all being required for the recited pharmaceutical composition.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1, 21-23, 30-32, and 48-58 are rejected under 35 U.S.C. 103 as being unpatentable over Vegge et al. (WO2018224689A2 in PTO-892 dated 01/21/25).
Vegge et al. teaches solid compositions for oral administration comprising (i) a GLP-1 derivative and the SGLT2 inhibitor dapagliflozin or (ii) a GLP-1 derivative and a salt of NAC (absorption enhancer) in combination with an SGLT2 inhibitor (see Abstract). Vegge et al. demonstrates a composition consisting of semaglutide (GLP-1 derivative), SNAC, and empaglifozin (see Table 9). Vegge et al. discloses the structure of SNAC below (see page 22 lines 15-20):
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Vegge et al. discloses that their SNAC can be a sodium salt form as recited in instant claim 21 (see page 22 lines 20-34). Vegge et al. discloses that the combination of empagliflozin and SNAC provided a synergistic effect on the permeability across the cellular monolayer of Caco-2 for semaglutide and FD4, indicating that oral bioavailability of peptides, such as semaglutide would be greater than the sum of its oral bioavailablity with dapagliflozin alone or SNAC alone (see page 40 lines 6-10). Vegge et al. teaches that the absorption enhancer in their composition can also be can be a salt of capric acid such as sodium caprate (see page 22 lines 4-13). Vegge et al. discloses their compositions are in a form of a tablet or capsule (see claim 11). Vegge et al. discloses that the composition comprises 5-300 mg SGLT2 inhibitor, 20-800 mg salt of NAC, such as SNAC, and optionally 0.1-100 mg GLP-1 derivative (see claim 7). Vegge et al. discloses that the absorption enhancer can be at least 60% (w/w) of the total weight of the composition (see page 22 lines 5-10), and further discloses that the total weight of their tablet composition can range from 150mg to 1000mg (see page 2 lines 15-18), which suggests that enhancers including SNAC and sodium caprate can be present in amounts of 90mg to 600mg (60% w/w of total composition).
Vegge et al. does not specifically demonstrate a composition comprising of multiple absorption enhancers as well as the recited amounts of 50-300 mg capric acid, 200-400 mg SNAC, and 1-100 mg empagliflozin. However, it would have been prima facie obvious before the effective filing date of the claimed invention to have included capric acid to the tablet composition comprising 0.1-100 mg semaglutide, SNAC, and empagliflozin disclosed in Vegge et al. and further prepare the recited amount of empagliflozin as well optimize the amounts and weight ratios of SNAC and capric acid to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Vegge et al. discloses that both the capric acid and SNAC are useful for the same purpose as absorption enhancers in the same tablet compositions. See In re Kerkhoven, MPEP 2144.06 I. Furthermore, Vegge et al. provides guidance that empagliflozin can be present in amounts of 50-300mg, which overlaps with the recited amount in the instant claims, rendering the claimed range obvious (see MPEP 2144.05 I). Lastly, Vegge et al. discloses that the absorption enhancer, which can include either SNAC or capric acid, can be present in amounts of 90-600mg. Therefore, an ordinary skilled artisan could have performed routine optimization to arrive at the claimed amounts of SNAC and capric acid as well as the claimed weight ratio between the two enhancers based on the amount ranges for the absorption enhancer disclosed in Vegge et al. See MPEP 2144.05 II.
Response to Arguments
Applicant’s arguments filed on 06/25/2025 have been fully considered in so far as they apply to the rejections of the instant office action, but were not persuasive.
Applicant states that the teachings of Vegge et al. focus on the alleged synergistic effect of dapagliflozin or empagliflozin with SNAC. Applicant states that a person of ordinary skill in the art reading Vegge would not have had a reason to add capric acid or salts thereof to the mixture of dapagliflozin or empagliflozin and SNAC. Applicant states that Vegge has not shown that dapagliflozin or emplagliflozin would have a synergistic effect with the use of capric acid or salts therefore. Therefore, Applicant states that capric acid and SNAC do not have the same purpose of being an absorption enhancer which synergistically combine with dapagliflozin or empagliflozin. Applicant further states that Vegge et al. does not teach or suggest that including additional absorption enhancers would be helpful for the composition of Vegge.
In response to these arguments, the assessment that the capric acid disclosed in Vegge does not have the same purpose as SNAC of being an absorption enhancer is not persuasive. While Vegge et al. does not provide an example of a composition comprising capric acid, Vegge et al. explicitly discloses that their invention includes other embodiments in which sodium caprate can be used as the absorption enhancer in their compositions, and conclusive proof of efficacy is not required to show a reasonable expectation of success as stated in MPEP 2143.02 I. Therefore, an ordinary skilled artisan could have reasonably expected that alternative disclosed absorption enhancers such as capric acid would also have a similar synergistic effect with dapagliflozin or empagliflozin. Furthermore, MPEP 2144.06 I states “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven”. Therefore, since both capric acid and SNAC are disclosed as being useful for the same purpose as absorption enhancers in the same type of composition, it is prima facie obvious to combine the two and form a third composition used for the very same purpose.
Applicant states that the claimed invention is based in part on the discovery that the combination of sodium caprate and SNAC achieves a synergistic effect in enhancing overall oral absorption of therapeutic agents. Applicant states that it was unexpectedly found that “the combinations of large and small molecules not only do not interfere with absorption of each entities, but also enhance the absorption and improve the time-course pharmacokinetic profiles of small molecules”. Applicant points to FIG. 6 of copending application 18/702,119 shown below, in which the combination of SNAC and sodium caprate achieved a much higher Cmax and AUC for semaglutide plasma concentration when compared to using SNAC or sodium caprate alone.
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Applicant further points to FIG.1 of the instant application, in which the addition of empagliflozin had no obvious effect on the absorption of semaglutide. Applicant states that this is contrary to the assertion made in Vegge, and Applicant further explains that the synergistic effect disclosed in Vegge requires that the concentration of empagliflozin be greater than 1.2 mM, which Applicant argues cannot be practically realized as solubility of empagliflozin is only about 1 mM according to Cayman chemicals.
In response to these arguments of unexpected results, the evidence of an unexpected result must compare the claimed invention with the closest prior art according to MPEP 816.02(e). Here, the closest prior art to compare to is Vegge et al. While Applicant has provided comparisons with SNAC and capric acid alone, this comparison is not the same as the compositions disclosed in Vegge. Examiner notes that in FIG. 6 of copending application 18/702,119 shown above, the composition only contains semaglutide and no SGLT-2 inhibitor as required in the instant claims. Therefore, a proper comparison to the closest prior art has not been made because Vegge et al. discloses compositions that include GLP-1 compounds, SGLT2 inhibitors, and an absorption enhancer such as SNAC or capric acid, and Applicant has not provided a comparison over this combination. Furthermore, Applicant demonstrates in FIG. 1 of the instant application that addition of empaglifozin to semaglutide and SNAC/capric acid had no effect, however this finding was not demonstrated with a composition comprising SNAC or capric acid alone as shown in Vegge. Furthermore, the assessment that the synergistic effect disclosed in Vegge et al. cannot be practically realized is not persuasive because Vegge et al. provides experimental data showing working ranges above 1 mM empagliflozin. Lastly, the evidence provided by Applicant is not sufficiently commensurate in scope of the instant claims because it is not clear if the argued synergistic effect would apply for any recited incretin compound. As disclosed in paragraph 0007 of the instant specification, Applicant states that the combinations of large and small molecule not only do not interfere with absorption of each entity, but also enhance the absorption and improve the time-course pharmacokinetic profiles of small molecules. The recited SGLT-2 inhibitors are all known small-molecule compounds as evidenced by Xie et al. (in PTO-892, see Abstract). However, not all incretins are considered large molecules according to Saxena et al. (in PTO-892), which discloses danuglipron (incretin) as a non-peptide small molecule GLP-1R agonist (see Abstract). Therefore, Applicant has not provided a sufficient number of incretin compositions (large and small incretin molecules) such that the synergistic effect being argued would apply for all recited incretins.
Applicant presents additional arguments against Pederson and Kidron, however the new rejection does not cite Pederson and Kidron, rendering Applicant’s arguments against these references moot.
Amended Rejections Necessitated by the Amendments filed on 07/17/2025
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 21-23, 30-32, and 48-58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 44-61 of copending Application No. 18/702,119 (‘119) in view of Vegge et al. (WO2018224689A2 in PTO-892 dated 01/21/25).
The claims of ‘119 recite a pharmaceutical composition for oral administration comprising a polypeptide such as semaglutide (claim 56 of ‘119), an aliphatic acid of Formula I such as capric acid (claim 46 of ‘119), and a compound of Formula II such as SNAC (claim 48 of ‘119). Claim 58 of ‘119 recites the composition is in the form of a solid oral dosage form. Claim 52 of ‘119 recites the weight ratio of aliphatic acid and the compound of Formula II ranges from 20:1 to 1:20. Claim 53 of ‘119 recites the amount of aliphatic acid is 50-300 mg, and Claim 54 of ‘119 recites the amount of compound Formula II is 200-400 mg. Furthermore, claim 59 of ‘119 recites a method of treating type-2 diabetes or obesity by orally administering the pharmaceutical composition.
The difference between the claims of ‘119 and the instant invention is that the claims of ‘119 do not recite a composition further comprising a SGLT-2 inhibitor such as empagliflozin.
The teachings of Vegge et al. are as described above. Furthermore, Vegge et al. teaches that their composition can be used to treat diabetes and/or obesity (see page 27, lines 20-22).
It would have been prima facie obvious to combine the claims of ‘119 with Vegge et al. before the effective filing date of the claimed invention by including an SGLT-2 inhibitor such as empagliflozin in the recited weight amount into the composition recited in the claims of ‘119 and further preparing the instantly recited amounts and weight ratio to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because both the claims of ‘119 and Vegge et al. teach a composition comprising an GLP-1 derivative (semaglutide) and an absorption enhancer (SNAC and/or capric acid) for oral administration that can be used to treat diabetes and/or obesity. See In re Kerkhoven, MPEP 2144.06 I. Furthermore, an ordinary skill artisan could have predictably prepared the weight amounts and weight ratios of the compounds recited in the instant claims since the claims of ‘119 and Vegge et al. disclose overlapping amounts and ratios (see MPEP 2144.05 I).
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant requests the provisional double patenting rejection to be held in abeyance until allowable subject matter is found. Since allowable subject matter has not yet been found, the provisional double patenting rejection over ‘119 is maintained.
Conclusion
No claim is found allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/D.H.C./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693