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 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.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 28 April, 2026 has been entered.
Claims Status
Claims 1-3, 10, 11, 17, 18, 24, 32, 33, 35, 39-41, 43, and 45-48 are pending.
Claims 1, 18, and 40 have been amended.
Claims 32, 33, and 35 have been withdrawn due to an election/restriction requirement.
Withdrawn Rejections
The rejection of claim 18 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, due to inability to have high bioavailability is hereby withdrawn due to amendment.
Maintained/Modified Rejections
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-3, 10, 11, 17, 18, 24, 39-41, 43, and 45-48 are rejected under 35 U.S.C. 103 as being unpatentable over Hammerle et al (Bone (2012) 50 p965-973) in view of Kidron et al (US 20110142800, previously cited)
Hammerle et al discuss a clinical trial examining the pharmacokinetics of orally administered teriparatide with an absorption enhancer, and discuss its applications in the treatment of osteoporosis (abstract). Dosages between 1 and 10 mg of teriparatide using 200 mg of CNAC (structurally very similar to SNAC of the instant claims), and 2.5-5 mg using 200 mg of CNAC were used (p967, 1st column, last paragraph, continues to 2nd column). Pharmacokinetics data shows generally increasing blood concentrations with dose, and similar timing of uptake and no significant differences between the 100 and 200 mg CNAC arms (table 2, p969, top of page). Note that the Cmax (74.1-1624 pg/mL) and AUC/Cmax (0.386-0.449h) from table 2 are, within the error of the measurements, in the range claimed by applicants, and that the Cmax of the more standard administration route was 149 pg/ml (table 2, p969, top of page). In other words, the dosages used were within the range of the therapeutic dosages, however, uncertainty is very large in all measurements.
The difference between this reference and the instant claims is that this reference uses a different permeation enhancer, and does not discuss soybean trypsin inhibitor.
Kidron et al discuss compositions for the oral administration of proteins (title), including parathyroid hormone (paragraph 33). Using oral dosing, the low patient compliance with injected dosage forms can be avoided (paragraph 2). This is accomplished using a protease inhibitor and an absorption enhancer (paragraph 13). The protease inhibitor can be soybean trypsin inhibitor (paragraph 50), applicant’s elected species of protease inhibitor. The protease inhibitor can be around 0.2 to 10 mg/dosage unit, or more (paragraph 56). The absorption enhancer can be SNAC (paragraph 65). The absorption enhancer can be almost all of the composition (99.4% w/w) (paragraph 68), or 70 mg or more per dosage unit (paragraph 70). Various dosage forms, including tablets, are discussed (paragraph 120). Magnesium stearate, applicant’s elected lubricant, is mentioned as useful for that purpose (paragraph 114). The composition can be formulated to achieve a particular release profile, as known by one skilled in the art (paragraph 115). Note that the protease inhibitor is synergistic with the permeation enhancer (paragraph 124); this means that, with the protease inhibitor, a lower pharmaceutical dose can be used. Examples are given with 2.5 mg aprotinin (protease inhibitor) and 6 mg insulin (paragraph 123). Optimizing the amount of the protease inhibitor (paragraph 128) and the uptake enhancer (paragraph 129) is mentioned.
Therefore, it would be obvious to use the SNAC of Kidron et al for the CNAC of Hammerle et al, as Kidron et al discuss both uptake inhibitors, and discuss optimizing the uptake inhibitor and the amount of the material. As this is standard pharmaceutical development, an artisan in this field would attempt this modification with a reasonable expectation of success.
Furthermore, it would be obvious to add soybean trypsin inhibitor as described by Kidron et al, to increase the amount of the peptide absorbed. As the reference clearly states that this will benefit uptake, an artisan in this field would attempt this addition with a reasonable expectation of success.
Finally, it would be obvious to optimize the concentrations of the elements in the tablet to reduce the amount of drug used while maintaining a pharmacologically appropriate dosage (as described by Hammerle et al). As Hammerle et al show that the uptake increases with increasing dosage, and Kidron et al describe ranges that overlap with applicant’s claimed formulations, an artisan in this field would attempt this modification with a reasonable expectation of success. Note that, absent secondary considerations, differences in concentration are not considered a patentable distinction (MPEP 2144.05(II)(A) and MPEP 2144.05(II)).
Hammerle et al discuss a very similar uptake enhancer to that claimed by applicants using teriparatide, showing pharmacokinetics very similar to that claimed by applicants. Kidron et al renders obvious optimizing the amount of teriparatide and soybean trypsin inhibitor, rendering obvious claims 1-3, 17, 24, and 39-41.
Kidron et al discuss adding magnesium stearate, a lubricant, rendering obvious claims 10, 11, and 45-47.
Hammerle et al show a bioavailability of around 1% (based on the comparison of Cmax values vs. SC injection) or 0.25% (based on applicant’s calculations in their dec, and optimizing the formulation would not be expected to decrease these values. Thus, the combination of references renders obvious claim 18.
response to applicant’s arguments
Applicants argue that the findings of Malkov et al cannot be extrapolated to sequences other than insulin, that the mechanism is contradicted by Aroda et al, argue that success is improved bioavailability, that the declaration of 20 Nov, 2025 (showing that three different peptides using SNAC technology failed) was not properly considered, that applicants are in the business of oral peptide drug delivery, so the attempts must be considered, that there is no reasonable expectation of success for substitution of SNAC for CNAC, that CNAC formulations have lower bioavailability and higher degradation rates than SNAC formulations, that Hammerle et al teaches away from the invention, that applicants have shown unexpected results of improved bioavailability with higher SNAC levels, argues that variability is high in such experiments (vs. an argument of lack of statistical significance), and that there is a need for the invention (presumably a long felt need argument). Some of these arguments are supported by a declaration by Gregory Burshtein, applicant.
Applicant's arguments filed 28 April, 2026 have been fully considered but they are not persuasive.
On 20 Nov, 2025, applicants submitted a declaration stating that (among other things), that a number of applicant’s projects had failed. No detail is given of the projects. Malkov et al was cited in the last office action to show that the outline of how SNAC works is known, and would not be expected to work for hydrophobic sequences – an argument that, as we don’t know anything about the failed projects except that they failed, it is not possible to show that this is unexpected or an indication of unpredictability. However, the evidence that applicants cite is unpersuasive. Applicants cite Aroda et al, which shows that a sequence with a lipophilic attachment was not assisted by SNAC. Note that the is the exact argument made in the previous office action; that a hydrophobic sequence would be less likely to be assisted by SNAC.
There are other issues with applicant’s argument. Patentability is determined as of applicant’s priority date based on what a person of skill in the art would believe (text of 35 USC 103); Aroda et al was published well after this date, and the data of applicant’s declaration would not be available to a person of skill in the art.
Applicants state that the failed programs did not improve bioavailability. That is not what the declaration states; it merely gives relatively low bioavailabilities. It is not clear how much effort was made to increase bioavailability, or if they were terminated prematurely due to non-scientific rationales, such as funding.
Even taken as applicants intend and in the best light possible, the fact that applicants can describe 3 failed projects is not sufficient to show that there is no reasonable expectation of success. In applicant’s declaration of 28 April, 2026, applicants admit that this is not an exhaustive list of all of the research programs. In other words, the declaration of 20 Nov, 2025 merely shows that applicant has had some projects that are unsuccessful. However, the Umbrex sales literature (downloaded 9 July, 2026) states that 90% of all drugs fail at the preclinical stage, with an additional 91% failing in clinical trials (4th page, section 3 “compare with industry benchmarks”). In other words, the fact that applicant has failed drug development programs is not unusual; it would be amazing if all their drug programs were successful.
In response to an argument that the declarations do not show statistical significance, applicants argue that this is a field with a great deal of variability. However, nowhere have applicants stated any law, regulation, court case, or logic as to why this means that statistical significance is not required. In science, statistical significance is required to show that two numbers are different; without it, the hypothesis has not been proven.
Applicant’s remaining arguments are a compilation of previously cited arguments, which were unpersuasive for reasons of record.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
first rejection
Claims 1-3, 6, 10, 11, 15, 17, 18, 20-24, and 39-44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 21 of copending Application No. 15/549418 (US 20180036234, cited by applicants) (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the competing claims render obvious the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Competing claim 21 is a method using a tablet formulation of teriparatide and SNAC orally administered, with similar pharmacokinetics and dosages.
response to applicant’s arguments
Applicants request that this rejection be deferred until a determination of allowable subject matter is made. However, until the rejection is overcome, it will remain valid.
second rejection
Claims 1-3, 6, 10, 11, 15, 17, 18, 20-24, and 39-44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15 and 16 of copending Application No. 15/549425 (US 20180028622, cited by applicants) (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the competing claims anticipate or render obvious the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The teachings of the competing claims are similar to the first double patenting rejection, as is the logic behind the rejection.
response to applicant’s arguments
Applicants request that this rejection be deferred until a determination of allowable subject matter is made. However, until the rejection is overcome, it will remain valid.
third rejection
Claims 1-3, 6, 10, 11, 15, 17, 18, 20-24, and 39-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5, and 6-9 of U.S. Patent No. 10,010,503 (previously cited) in view of Kidron et al (US 20110142800, previously cited). Please note that this rejection is necessitated by amendment.
The teachings of the competing claims are similar to the previous rejections under this basis, save that the competing claims do not discuss a tablet formulation.
Kidron et al discuss compositions for the oral administration of proteins (title), including parathyroid hormone (paragraph 33). Using oral dosing, the low patient compliance with injected dosage forms can be avoided (paragraph 2). This is accomplished using a protease inhibitor and an absorption enhancer (paragraph 13). The absorption enhancer can be SNAC (paragraph 65). The absorption enhancer can be 40-60% (w/w) of the composition (paragraph 68), or 50 mg or more per dosage unit (paragraph 70). Various dosage forms, including tablets, are discussed (paragraph 120).
Therefore, it would be obvious to use a tablet formulation, as Kidron et al teach that this can be used for similar formulations. As Kidron et al discuss much the same formulations, an artisan in this field would attempt this variation with a reasonable expectation of success. Note that this is a simple substitution of one known element (the unnamed dosage form of the competing claims) for another (the dosage forms of Kidron et al) yielding expected results (a usable dosage form).
response to applicant’s arguments:
Applicants request that this rejection be deferred until a determination of allowable subject matter is made. However, until the rejection is overcome, it will remain valid.
fourth rejection
Claims 1-3, 6, 10, 11, 15, 17, 18, 20-24, and 39-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 6, and 10 of US Patent No. 12,076,373.
The teachings of the competing claims and the logic of the rejection are similar to that of the first ODP rejection, and will not be repeated here.
response to applicant’s arguments:
Applicants request that this rejection be deferred until a determination of allowable subject matter is made. However, until the rejection is overcome, it will remain valid.
fifth rejection
Claims 1-3, 10, 11, 17, 18, 24, 39, 40, 41, 43, and 45-48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 6 of Application No. 18/432,185 (US 20240181020).
Competing claim 1 describes a method of treatment using oral dosing of parathyroid hormone and SNAC, so that the plasma concentration (Cmax) is between 25-1000 pg/mL. Competing claims 2-4 and 6 describe protease inhibitors, narrowing down to soybean trypsin inhibitor.
The difference between the competing claims and the examined claims is that the competing claims do not describe the ratios of the claims. However, differences in concentration are not considered a patentable distinction, as these are commonly optimized (MPEP 2144.05(II)(A)). Alternatively, Kidron et al (US 20110142800, previously cited), discussing similar inventions, describes optimizing the concentration of the protease inhibitor and the absorption enhancer (paragraphs 128-129); presumably, the amount of the pharmaceutical would be appropriate for a pharmacological effect.
response to applicant’s arguments:
Applicants request that this rejection be deferred until a determination of allowable subject matter is made. However, until the rejection is overcome, it will remain valid.
sixth rejection
Claims 1-3, 10, 11, 17, 18, 24, 39, 40, 41, 43, and 45-48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 10, and 19 of Application No. 18/841,379 in view of Kidron et al (US 20110142800, previously cited).
Competing claim 1 describes a formulation with a parathyroid hormone and an absorption enhancer. Competing claim 7 specifies that the absorption enhancer is NAC, the free acid of SNAC, and assumed to be equivalent. Competing claim 10 specifies that the absorption enhancer be at least a large percentage of the total, while competing claim 19 states that the parathyroid hormone is selected from a small group including teriparatide.
The difference between the competing claims and the examined claims is that the competing claims do not give the ratios of the examined claims, nor does it describe a protease inhibitor.
Kidron et al describes similar formulations to the competing claims, comprising a polypeptide and SNAC, along with a protease inhibitor (paragraph 8). The protease inhibitor protects the protein of the formulation from cleavage (paragraph 48). Soybean trypsin inhibitor is suggested as an appropriate protease inhibitor (paragraph 50). PTH is listed as a polypeptide that can be used in the invention (paragraph 33).
Therefore, it would be obvious to include soybean trypsin inhibitor to the formulation of the competing claims, as Kidron et al states that this will prevent cleavage of the polypeptide. As this reference describes formulations similar to those of the competing claims, an artisan in this field would attempt this modification with a reasonable expectation of success. Note that differences in concentration are not considered a patentable distinction
response to applicant’s arguments:
Applicants request that this rejection be deferred until a determination of allowable subject matter is made. However, until the rejection is overcome, it will remain valid.
seventh rejection
Claims 1-3, 10, 11, 17, 18, 24, 39, 40, 41, 43, and 45-48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9, 11, and 13 of Application No. 18/818,691 in view of Kidron et al (US 20110142800, previously cited).
Competing claim 9 describes a kit with a parathyroid hormone and NAC, the free acid of SNAC, and assumed to be equivalent. Competing claim 11 specifies that the absorption enhancer be at least a large percentage of the total, while competing claim 13 states that the parathyroid hormone is selected from a small group including teriparatide.
The difference between the competing claims and the examined claims is that the competing claims do not give the ratios of the examined claims, nor does it describe a protease inhibitor.
Kidron et al describes similar formulations to the competing claims, comprising a polypeptide and SNAC, along with a protease inhibitor (paragraph 8). The protease inhibitor protects the protein of the formulation from cleavage (paragraph 48). Soybean trypsin inhibitor is suggested as an appropriate protease inhibitor (paragraph 50). PTH is listed as a polypeptide that can be used in the invention (paragraph 33).
Therefore, it would be obvious to include soybean trypsin inhibitor to the formulation of the competing claims, as Kidron et al states that this will prevent cleavage of the polypeptide. As this reference describes formulations similar to those of the competing claims, an artisan in this field would attempt this modification with a reasonable expectation of success.
Note that differences in concentration are not considered a patentable distinction, as these are commonly optimized (MPEP 2144.05(II)(A)). Alternatively, Kidron et al describes optimizing the concentration of the protease inhibitor and the absorption enhancer (paragraphs 128-129); presumably, the amount of the pharmaceutical would be appropriate for a pharmacological effect.
response to applicant’s arguments:
Applicants request that this rejection be deferred until a determination of allowable subject matter is made. However, until the rejection is overcome, it will remain valid.
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 FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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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.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
