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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 15 Oct, 2025 has been entered.
Claims Status
Claims 45-53 are pending.
Claim 45 has been amended.
Claims 46-53 are new.
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.
Claim(s) 16, 22, 23, 25, 33-35, 39, and 41-45 are rejected under 35 U.S.C. 103 as being unpatentable over Brixen et al (Basic Clin. Pharmcol. Toxicol. (2004) 94 p260-270, previously cited) in view of Kidron et al (US 20110142800, cited by applicants), and Hammerle et al (Bone (2012) 50 p965-973, previously cited).
Applicants are claiming a method of treating osteoporosis, comprising administering a formulation comprising PTH, SNAP, and soybean trypsin inhibitor. Dependent claims require no additional ingredients other than lubricant, and specify dosing schedules and pharmacokinetics.
Brixen et al discuss teriparatide, a fragment of parathyroid hormone, for treatment of osteoporosis (title). This has been demonstrated to provide impressive increases in bone density, and to greatly reduce the risk of fracture; this is considered a breakthrough in the treatment of severe osteoporosis (abstract).
The difference between this reference and the instant claims is that this reference does not discuss oral administration of teriparatide, with a formulation comprising SNAC and a protease 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 absorption enhancer can be SNAC (paragraph 65). 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). A range of concentrations of the adsorption enhancer can be used (paragraph 68), and the amount of both the absorption enhancer and the protease inhibitor can be optimized (paragraphs 128 and 129). This reference teaches oral dosing of polypeptide drugs, including parathyroid hormone, using SNAC.
Hammerle et al discuss a clinical trial examining the pharmacokinetics of orally administered teriparatide with an absorption enhancer with an intent of treating 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-.449h) from table 2 are mostly 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. Blood concentrations that are therapeutically relevant were achieved (p972, 1st column, 2nd paragraph). Note that SC injection, the standard for this drug, is daily (p966, 1st column, 2nd paragraph). This reference shows that the pharmacokinetics claimed by applicants is similar to the known pharmacokinetics for a similar material.
Therefore, it would be obvious to use the oral formulations of Kidron et al for the therapy of Brixen et al, for better patient compliance, as described by Kidron et al. As Hammerle et al show that a similar formulation can achieve therapeutically relevant plasma concentrations, an artisan in this field would attempt this formulation with a reasonable expectation of success.
Brixen et al teaches that teriparatide is useful for the treatment of osteoporosis. Kidron et al teach formulations of SNAC, therapeutic, protease inhibitor, including soybean trypsin inhibitor, and magnesium stearate for oral administration of peptide drugs. While the reference does not give the claimed amounts of SNAC and protease inhibitor, Kidron et al explicitly discusses optimizing the amounts of these compounds. Once the formulation is optimized, dosing is scaled to achieve the therapeutic plasma concentration, the levels of which are discussed by Hammerle et al. The MPEP states that “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or working ranges by routine experimentation" In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) (MPEP2144.05.II). This will reasonably generate the claimed formulations consisting of teriparatide, SNAC, soybean trypsin inhibitor, and magnesium stearate for treating osteoporosis, rendering obvious claims 45 and 50-52..
The CNAC of Hammerle et al is structurally similar to the SNAC used by Kidron et al, so would be expected to have a similar mechanism of action. This would reasonably give a similar time for the material to move from the digestive tract to the blood. With the dose (and hence the Cmax) set by the desired plasma concentration, this will give pharmacokinetics similar to that seen (and claimed) by applicants. Note that the pharmacokinetic parameters claimed by applicants are met by Hammerle et al, within the accuracy of the measurement. Thus, the combination of references renders obvious claims 47-49.
Hammerle et al discusses daily dosing, which presumably will require repeats (otherwise, it’s a single dose, not daily). Thus, the combination of references renders obvious claims 46-53.
response to applicant’s arguments
Applicants argue that there is no reasonable expectation of success, that Kidron et al discusses insulin and exenatide, not teriparatide, that SNAC and CNAC would not be expected to give similar pharmacokinetics, claim an unexpected result of variation of SNAC concentration provide improved bioavailability, claim an unexpected result of the claimed formulation suitable for use, and claim an unexpected result of reduced bone resorption. These arguments are supported by a declaration by Prof. Greg Burshtein, applicant.
Applicant's arguments filed 15 Oct, 2025 have been fully considered but they are not persuasive.
Applicants argue that there is no reasonable expectation of success, based on a reference published after applicant’s priority date discussing the difficulties in oral peptide availability and Prof. Burshtiein’s failed experiments with other polypeptide drugs. For the reference, it is not clear what an expectation of success is based on the reference; note that applicants have demonstrated vary low bioavailability and a large amount of variability (based on the large standard deviations of their experiment). Furthermore, the primary reference demonstrates success in getting physiologically relevant amounts into the bloodstream using a method vary similar to applicants. Applicants argue that the inventors have failed with other peptide drugs. However, it’s not clear what applicants consider a ‘success,’ it’s not clear how many different polypeptide drugs applicants have attempted to develop, it’s not clear if the data given is after optimization or not, it’s not clear if this data was developed just for this invention to show unpredictability. The MPEP states that the failure of experimenters who have no interest in succeeding should not be accorded great weight (MPEP 716.07). Nor is clear if this is unexpected; it’s known in the art that SNAC works by weakly binding to the therapeutic, making it more hydrophobic so able to diffuse across gastrointestinal barriers (Malkov et al, Curr. Drug Deliv. (2005) 2 p191-197, p197, 1st column, 2nd paragraph). However, a more hydrophobic therapeutic would logically benefit less, as it is already hydrophobic. The hydrophobicity of the compounds used by applicants in their argument are not disclosed.
Applicants argue that Kidron et al discusses insulin and exenatide, not teriparatide. While the examples are directed to those two drugs, the disclosure of the reference is much broader, and explicitly mentions parathyroid hormone, a genus that includes teriparatide.
Applicants argue that SNAC and CNAC would be expected to give different pharmacokinetics. CNAC has the structure
PNG
media_image1.png
97
286
media_image1.png
Greyscale
. SNAC has the structure
PNG
media_image2.png
192
281
media_image2.png
Greyscale
. The ONLY difference is the chloride on CNAC that is not found on SNAC. Compounds with similar structures are expected to have similar properties (MPEP 2144.09(I)). These two compounds have similar structures, and are used for the same purpose. A person of skill in the art would expect them to work by a similar mechanism – weak absorption onto the therapeutic, increasing its lipophilicity to increase absorption from the digestive tract (Malkov et al, Curr. Drug Deliv. (2005) 2 p191-197). Applicants point to other differences in effect, but they do not say anything about the mechanism of uptake.
Applicants argue that increasing the ratio of SNAC to teriparatide increases bioavailability, an alleged unexpected result. There are a number of issues with the data underlying the argument. First, as the amount of SNAC is varied, the difference is made up with sodium starch glycolate, which applicants state can potentiate SNAC activity (paragraph 25 of Prof. Burshtein declaration). In other words, the different doses are not an apples to apples comparison. Second, applicants have previously demonstrated that varying the amount of SNAC can affect dissolution in different applications. It is not clear if applicants have optimized their tableting procedure for each formulation for optimum dissolution; the results applicants are demonstrating could just be differences in this parameter due to insufficient optimization. Third, it is the burden on applicants to show that the results are statistically significant (MPEP 716.02(b)). There is no mention of statistical significance in the declaration, but the means±SD overlap for most of the comparisons, strongly suggesting a lack of statistical significance. Finally, it is not clear why this is considered unexpected. The only evidence that applicants have given that a person of skill in the art would assume otherwise is an experiment of Hammerle et al, which has large error bars. But, Hammerle et al does not say that the concentration of absorption enhancer has no effect, just that it was not measured over a small range – if it was over all concentrations, it would have no effect and could be left out of the formulation. Furthermore, the mechanism of action is weakly binding to the protein to make it more lipophilic so it will diffuse out of the gastrointestinal tract and increase protease resistance (Malkov et al, Curr. Drug Deliv. (2005) 2 p191-197, p197, 1st column, 2nd paragraph). Given that this is a binding, it can be saturated, and a person of skill in the art would also appreciate that the soybean trypsin inhibitor, also a protein and included in a large excess over the therapeutic, would also be bound, requiring more of the absorption enhancer to saturate. In other words, a person of skill in the art would expect a non-linear saturable effect of varying the amount of SNAC.
Applicants argue that the formulation works is unexpected, and that it has superior pharmacokinetics over SC administration, as it has faster uptake. It is not clear how a formulation working much as the rejection suggests is unexpected. But it is known that SC administration leads to relatively slow uptake (Richter et al, Drug Metab. Dispos. (2014) 42 p1881-1889, abstract), and oral uptake can be rapid (Teja-Isavadharm et al, Br. J. Clin. Pharmacol. (1996) 42 p599-604).
Finally, applicants argue that the formulation unexpectedly leads to lower bone resorption. Applicants have stated (declaration of 15 Oct, 2025) that it is known in the art that intermittent high doses leads to increase in bone mass, while prolonged exposure leads to resorption (paragraph 47). So the more rapid oral uptake compared to the slow SC uptake would be expected to produce this effect. In addition, it is not clear if this is different than the closest prior art (MPEP 716.02(e)), which uses CNAC in oral uptake, or if it is statistically significant compared to the SC administration (MPEP 716.02(b)(I)).
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 45-53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 21, 48, and 49 of copending Application No. 15/549,418 in view of Brixen et al (Basic Clin. Pharmacol. Tox. (2004) 94 p260-270) and Morin et al (AAPS PharmSciTech (2013) 14(3) p1158-1170).
Competing claim 21 describes a method using tablet formulations of SNAC, teriparatide, and soybean trypsin inhibitor, similar to instant claim 15, used for a different (but related) condition, with similar pharmacokinetic parameters. Comepting claims 48 and 49 specify a lubricant, while competing claim 49 specifies consisting of language.
The difference between the competing claims and the instant claims is that the disorder is different and does not specify the lubricant.
Brixen et al teaches the same therapeutic as the competing claims for the treatment of osteoporosis, the disorder of the instant claims (title). Therefore, it would be obvious to use the method of the competing claims for the treatment of the disorder of Brixen et al, as a simple substitution of one known element for another yielding expected results.
Morin et al states that magnesium stearate is the most commonly used lubricant for pharmaceutical tableting (p1158, 1st column, 3d paragraph). Therefore, it would be obvious to use the magnesium stearate as a lubricant, as Morin et al states that this material is used for this purpose. As this is the most commonly used lubricant, an artisan in this field would attempt the formulation with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
response to applicant’s arguments:
Applicants have requested that this rejection be held in abeyance until the identification of allowable subject matter. However, until the rejection is overcome, it will remain valid.
second rejection
Claims 45-53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 20 - 23 of US Patent No. 10,583,177 in view of Brixen et al (Basic Clin. Pharmacol. Tox. (2004) 94 p260-270) and Morin et al (AAPS PharmSciTech (2013) 14(3) p1158-1170).
Competing claim 1 describes a formulation of a therapeutic and SNAC, while competing claim 2 describes a protease inhibitor. Competing claims 20 and 21 specify the therapeutic be a polypeptide, specifically, a Markush group comprising a parathyroid hormone. Competing claim 22 describes a tablet (although worded as a core/shell rather than a tablet). Competing claim 23 specifies using this formulation to orally treat a disorder treatable by the therapeutic.
The difference between the competing claims and the instant claims is that the competing claims do not discuss pharmacokinetics, dosages, or treatment of osteoporosis.
Brixen et al teaches the same therapeutic as the competing claims for the treatment of osteoporosis, the disorder of the instant claims (title). Therefore, it would be obvious to use the method of the competing claims for the treatment of the disorder of Brixen et al, as a simple substitution of one known element for another yielding expected results.
Morin et al states that magnesium stearate is the most commonly used lubricant for pharmaceutical tableting (p1158, 1st column, 3d paragraph). Therefore, it would be obvious to use the magnesium stearate as a lubricant, as Morin et al states that this material is used for this purpose. As this is the most commonly used lubricant, an artisan in this field would attempt the formulation with a reasonable expectation of success.
response to applicant’s arguments:
Applicants have requested that this rejection be held in abeyance until the identification of allowable subject matter. However, until the rejection is overcome, it will remain valid.
third rejection
Claims 45-53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10, and 11 and 32 of copending Application No. 15/549,394 in view of Brixen et al (Basic Clin. Pharmacol. Tox. (2004) 94 p260-270).
Competing claim 1 describes a tablet composition with a therapeutic and SNAC and a protease inhibitor and teriparatide, while competing claims 10 and 11 require a lubricant, specifically, magnesium stearate. Competing claim 32 requires oral administration of these compositions to treat a disorder treatable by the therapeutic.
The difference between the competing claims and the instant claims is that the competing claims do not discuss the disorder, nor do they give the dose/schedule or pharmacokinetics.
Brixen et al teaches the same therapeutic as the competing claims for the treatment of osteoporosis, the disorder of the instant claims (title). Therefore, it would be obvious to use the method of the competing claims for the treatment of the disorder of Brixen et al, as a simple substitution of one known element for another yielding expected results.
Furthermore, it would be optimize the dose and dose schedule, which will necessarily yield the claimed pharmacokinetics. The MPEP states that “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or working ranges by routine experimentation" In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) (MPEP2144.05.II).
response to applicant’s arguments:
Applicants have requested that this rejection be held in abeyance until the identification of allowable subject matter. However, until the rejection is overcome, it will remain valid.
fourth rejection
Claims 45-53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8-13, and 17 of US Patent No. 12,239,691 in view of Di Prospero (slides from 18 March 2014 presentation at TechTank), Brixen et al (Basic Clin. Pharmacol. Tox. (2004) 94 p260-270), the Roche sales literature for protease inhibition (2004) and Morin et al (AAPS PharmSciTech (2013) 14(3) p1158-1170).
Competing claim 1 describes an oral dosage form comprising an absorption enhancer selected from a group that includes NAC (the free acid of SNAC, and considered equivalent). Competing claims 35-37 require narrower and narrower genera of compounds, terminating with teriparatide. Competing claim 39 describes a method of treatment of a condition treatable by oral administration of parathyroid hormone.
The difference between the competing claims and the instant claims is that the competing claims do not give as much detail as some of the instant claims, does not specify a tablet formulation, and does not specify treatment of osteoporosis.
DiProspero teaches that tablet/capsules are, by far, the preferred dosage form, due to ease of administration, ease of identification, and acceptable taste (p4). This renders obvious a tablet formulation.
Brixen et al teaches the same therapeutic as the competing claims for the treatment of osteoporosis, the disorder of the instant claims (title).
The Roche sales literature for protease inhibitors discusses protease inhibitors (title). Aprotinin inhibits plasmin, kallikrein, trypsin, and chymotrypsin (p10, 2nd entry into the table), while soybean trypsin inhibitor inhibits similar enzymes (p12, bottom of page). Note that the differences are not digestive enzymes; these two inhibitors would reasonably be expected to inhibit digestive enzymes similarly.
Morin et al states that magnesium stearate is the most commonly used lubricant for pharmaceutical tableting (p1158, 1st column, 3d paragraph).
Therefore, it would be obvious to use the method of the competing claims for the treatment of the disorder of Brixen et al, as a simple substitution of one known element for another yielding expected results.
Furthermore, it would be obvious to formulate the compounds with a tablet formulation, as DiProspero teaches that this is one of the greatly preferred dosage forms. As tableting is well known in the art, an artisan in this field would attempt this dosage form with a reasonable expectation of success.
Next, it would be obvious to add a protease inhibitor, such as soybean trypsin inhibitor, to reduce protease activity upon dosage. As this compound is known for this purpose, an artisan in this field would add this material with a reasonable expectation of success.
In addition, it would be obvious to optimize the dose and dose schedule, to optimize the pharmacokinetics and efficacy. The MPEP states that “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or working ranges by routine experimentation" In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) (MPEP2144.05.II).
Finally, it would be obvious to use the magnesium stearate as a lubricant, as Morin et al states that this material is used for this purpose. As this is the most commonly used lubricant, an artisan in this field would attempt the formulation with a reasonable expectation of success.
response to applicant’s arguments:
Applicants have requested that this rejection be held in abeyance until the identification of allowable subject matter. However, until the rejection is overcome, it will remain valid.
fifth rejection
Claims 45-53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6, and 10 of US Patent No. 12,076,373 in view of Brixen et al (Basic Clin. Pharmacol. Tox. (2004) 94 p260-270, previously cited).
The teachings of the competing claims and the logic of the rejection is similar to the first rejection for double patenting, above, and will not be repeated here.
response to applicant’s arguments:
Applicants have requested that this rejection be held in abeyance until the identification of allowable subject matter. However, until the rejection is overcome, it will remain valid.
sixth rejection
Claims 45-53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2-4, 6, 8, and 12 of copending Application No. 18/432,185 (US20240181020) in view of Di Prospero (slides from 18 March 2014 presentation at TechTank), and Brixen et al (Basic Clin. Pharmacol. Tox. (2004) 94 p260-270).
Competing claim 1 describes a method of treating hypoparathyroidism, comprising administering via oral ingestion a composition comprising a parathyroid hormone and SNAC, with a defined Cmax. Competing claim 2 specifies teriparatide, while competing claims 3, 4, and 6 specify a protease inhibitor, specifically, soybean trypsin inhibitor. Competing claim 8 specifies the amount of the PTH, while competing claim 12 specifies once or twice per day.
The difference between the competing claims and the examined claims is that the competing claims do not specify a tablet, discuss a different disorder, and don’t discuss the amount of SNAC.
DiProspero teaches that tablet/capsules are, by far, the preferred dosage form, due to ease of administration, ease of identification, and acceptable taste (p4). This renders obvious a tablet formulation.
Brixen et al teaches the same therapeutic as the competing claims for the treatment of osteoporosis, the disorder of the instant claims (title).
Therefore, it would be obvious to use a tablet formulation, as DiProspero teaches that this is the preferred dosage form. As tablets are common in the art, an artisan in this field would use this formulation with a reasonable expectation of success.
Furthermore, it would be obvious to use the formulation of the competing claims to treat osteoporosis, as Brixen et al teaches that this drug is useful for that disorder. As this is a known treatment for this disorder, an artisan in this field would attempt this therapy with a reasonable expectation of success.
The competing claims define an oral formulation with PTH, SNAC, and soybean trypsin inhibitor, using the same amount of PTH. DiProspero teaches using tablets, and Brixen et al teaches using this drug for treating osteoporosis. While the amount of SNAC is not defined, it is considered obvious to optimize this parameter to generate an effective uptake of the drug (MPEP 2144.05(II)). Thus, the combination of references renders obvious claims 15, 39, 41 and 45.
The competing claims specify teriparatide, rendering obvious claim 16.
The competing claims discuss once daily dosing, rendering obvious claims 22 and 33.
The competing claims give similar Cmax values, rendering obvious claims 23 and 34.
While none of the references discuss the AUC to Cmax ratio, this is the same therapeutic in a very similar formulation, which means that this value will necessarily be very similar. Thus, the combination of references renders obvious claims 25 and 35.
response to applicant’s arguments:
Applicants have requested that this rejection be held in abeyance until the identification of allowable subject matter. However, until the rejection is overcome, it will remain valid.
seventh rejection
Claims 45-53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 7, and 8 of copending Application No. 18/818,691(US20240415936) in view of Di Prospero (slides from 18 March 2014 presentation at TechTank) and the Roche sales literature for protease inhibition (2004).
Competing claim 1 specifies a method of treating a disorder, specified as a Markush group including osteoporosis in competing claim 8, comprising administering the patient a formulation of PTH and an absorption enhancer. Competing claim 2 specifies the amount of the absorption enhancer, while competing claim 4 specifies teriparatide as the PTH. Competing claim 7 specifies SNAC or SNAD.
The difference between the competing claims and the examined claims is that the competing claims do not specify a tablet formulation, the protease inhibitor, or the amounts of the other ingredients.
DiProspero teaches that tablet/capsules are, by far, the preferred dosage form, due to ease of administration, ease of identification, and acceptable taste (p4). This renders obvious a tablet formulation.
The Roche sales literature for protease inhibitors discusses protease inhibitors (title). Aprotinin inhibits plasmin, kallikrein, trypsin, and chymotrypsin (p10, 2nd entry into the table), while soybean trypsin inhibitor inhibits similar enzymes (p12, bottom of page). Note that the differences are not digestive enzymes; these two inhibitors would reasonably be expected to inhibit digestive enzymes similarly.
Therefore, it would be obvious to administer the dosage forms of the competing claims as a tablet, as DiProspero teaches that these are, by far the preferred dosage form. As they are common in the art, an artisan in this field would use this formulation with a reasonable expectation of success.
Furthermore, it would be obvious to add the soybean trypsin inhibitor of the Roche sales literature, to reduce protease activity. As the material is designed to do exactly that, an artisan in this field would attempt this with a reasonable expectation of success.
Finally it differences in concentration are not considered a patentable distinction, absent secondary considerations, as these parameters are routinely optimized (MPEP 2144.05(II)).
response to applicant’s arguments:
Applicants have requested that this rejection be held in abeyance until the identification of allowable subject matter. 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.
Examiner interviews are available via telephone 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.
/FRED H REYNOLDS/Primary Examiner, Art Unit 1658