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 .
DETAILED ACTION
The amendment after non-final office action filed August 25, 2025 is acknowledged. Claims 2-3, 10-11, 15 were cancelled, claims 9, 12 were amended and claims 1, 4-9, 12-14, 16 are pending.
*After further review, a second Non-Final office action follows.
Election/Restrictions
The restriction requirement was deemed proper and made FINAL previously. Claims 1, 4-8 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 9, 12-14, 16 are examined on the merits of this office action.
Withdrawn Objections/Rejections
The rejection of claims 9, 12-16 on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of US Patent No. 11389474 B2(reference application) in view of Swallowing Difficulties (https://www.swallowingdifficulties.com/healthcare-professionals/prescribing-different-formulations/different-coatings, “Different coatings”, posted online 2009) is withdrawn in view of the filing and approval of the terminal disclaimer on August 25, 2025.
The rejection of claims 9, 12-14 and 16 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in view of amendment of the claims filed August 25, 2025.
Terminal Disclaimer
The terminal disclaimer filed on August 25, 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent No. 11389474 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Maintained Revised Rejections
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 9 and 12 remain rejected under 35 U.S.C. 103 as being unpatentable over Gellman (US20140378382, cited previously) in view of Aungst (The AAPS Journal, Vol. 14, No. 1, March 2012, cited previously) and EFSA (The EFSA Journal (2009) 1114, 1-23, cited previously).
Instant claim 9 requires a specific PTH analogue (abaloparatide), a metal containing compound such as manganese chloride or manganese gluconate, a reducing agent such as lactose, ascorbic acid, tocopherol or vitamin A, and an absorption enhancer.
Regarding claims 9 and 12, Gellman discloses a pharmaceutical formulation comprising PTH analogues (see claims 1 and 2) in combination with manganese and vitamin C (reducing agent) (see paragraph 0071) and for oral administration (see paragraph 0081). Regarding the limitation of the PTH analog of teriparatide or abaloparatide, Gellman teaches various PTH analogues including abaloparatide (see claim 1, BA058 is abaloparatide) and an effective amount for the desired therapeutic activity (see claim 20).
Gellman teaches nutritional formulations comprising the PTH analogues and inclusion of manganese (a metal) and vitamin C (abscorbic acid) as part of the nutritional formulation (commonly included vitamins and minerals for nutrition) (see paragraph 0071). Gellman teaches nutritional formulations comprising lactose, another commonly added carbohydrate to nutritional/pharmaceutical formulations (see paragraph 0079),
Gellman is silent to the composition specifically comprising an absorption enhancer and a manganese salt such as manganese chloride or gluconate.
However, Aungst teaches “Absorption enhancers are functional excipients included in formulations to improve the absorption of a pharmacologically active drug” (see abstract). Aungst teaches examples of permeation enhancers (see Table III) which is inclusive to fatty acids and salts thereof amongst other known agents.
EFSA teaches that “In 1999, the SCF estimated that the use of manganese carbonate, chloride, citrate, gluconate, glycerophosphate and sulphate were acceptable sources of manganese for use in the manufacture of foods for particular nutritional purposes” (See page 11, paragraph 0001). EFSA teaches Manganese dichloride, gluconate, sulfate and citrate salts are affirmed as Generally Recognized as Safe (GRAS) in the United States and can be used as an ingredient in certain foods with no limitation other than current good manufacturing practices and in nutrient supplements” (see page 11, paragraph 0004). EFSA further teaches Ascorbate (vitamin C) as a supplement and for nutritional purposes in food (see pages 12-13).
It would have been obvious before the effective filing date of the claimed invention to include an absorption enhancer to improve the absorption of the PTH analog in combination with the manganese and vitamin C/ascorbic acid for nutritional purposes. One of ordinary skill in the art would have been motivated to do so to enhance absorption of the drug which in turn would allow for greater therapeutic effectiveness. There is a reasonable expectation of success given that absorption enhancers are commonly used excipients used in oral formulations to improve uptake of the drug.
Regarding manganese gluconate and vitamin C/ascorbic acid, it would have been obvious before the effective filing date of the claimed invention to use manganese gluconate as the source of manganese and vitamin C in the nutritional formulation of Gellman. One of ordinary skill in the art would have been motivated to do so because Manganese gluconate is affirmed as Generally Recognized as Safe (GRAS) in the United States and can be used as an ingredient in certain foods with no limitation other than current good manufacturing practices and in nutrient supplements. One of ordinary skill in the art would have been motivated given both vitamin C and manganese are routinely used vitamins and minerals used in nutritional formulation with the purpose of providing nutrition to the subject. There is a reasonable expectation of success given that manganese gluconate is well known, safe source of manganese supplementation in humans and both manganese and vitamin C are routinely used in nutritional formulations for the purpose of providing nutrition.
Furthermore, the use of manganese salts, ascorbic acid and absorption enhancers such as fatty acids represents routine selection of known excipients that perform their predictable functions in oral peptide formulations (nutritional source, reducing agent and absorption enhancer) (see MPEP 2143(1)(B)). Combining familiar elements according their established functions (as stated above) to obtain predictable results is considered obvious. A reasonable expectation of success existed because Gellman teaches that manganese and vitamin C may be included (along with other reducing agents) in oral formulations of PTH analogues, even though in a list. Their disclosed compatibility with PTH analog compositions would have led to a person of ordinary skill in the art to expect predictable performance when used in the claimed formulation (see MPEP 2143).
Regarding the functional limitation of “wherein said composition upon oral administration provides relative bioavailability of at least 0.5% compared to subcutaneous administration”, the composition of Gellman in view of Aungst and EFSA is the same as the instant claims and thus, would inherently have this property upon oral administration.
Response to Applicant’s Arguments
Applicants argue “The cited references, either alone or in combination, do not teach or suggest the claimed metal containing compounds and the claimed reducing agents. Also, Gellman relates to development of new analogs of PTH which is different from development of improved oral formulation of PTH analogs. Applicant notes that peptide synthesis research is difference from pharmaceutical/biotech formulation research. Further, Gellman does not relate to peptide formulation delivery. Rather, Gellman focuses on synthesis of new PTH analogues. There is no mention of bioavailability challenges in oral delivery of PTH analogues in Gellman. Also, there is no guidance in Gellman on how to improve bioavailability. Accordingly, one of ordinary skill in the art working on developing pharmaceutical composition (formulation of PTH analogue) would not have referred to Gellman as it relates to synthesis of peptide. Further, Gellman teaches generally nutritional compositions in paragraphs [0068] - [0076] and pharmaceutical compositions in paragraphs [0077] - [0082]. Nutritional formulations are distinctly defined in Gellman compared to pharmaceutical composition as shown in paragraphs [0072] and [0073] of Gellman (also shown below). [0072] Examples of nutritional compositions disclosed herein include but are not limited to infant formulas, dietary supplements, dietary substitutes, and rehydration compositions. Nutritional compositions of particular interest include but are not limited to those utilized for enteral and parenteral supplementation for infants, specialist infant formulas, supplements for the elderly, and supplements for those with hyperglycemia. [0073] The nutritional composition of the present invention may also be added to food even when supplementation of the diet is not required. For example, the composition may be added to food of any type including but not limited to margarines, modified
butters, cheeses, milk, yoghurt, chocolate, candy, snacks, salad oils, cooking oils, cooking fats, meats, fish and beverages(emphasis added.) In Gellman, manganese and vitamin C are only disclosed in relation to nutritional compositions, not pharmaceutical compositions. In contrast, the claimed invention relates to an oral pharmaceutical composition with therapeutically effective amount of PTH analog.
Still further, Gellman teaches generally a large list of ingredients for nutritional compositions. Vitamin C and manganese are disclosed among a large number of excipients. However, there is no apparent reason for one of ordinary skill in the art to particularly select Vitamin C and manganese from the large number of excipients, and use them together. There are no examples in Gellman using them either individually or in combination. Also, emphasis must be kept on such disclosure being very generalized and for nutraceutical composition. There is insufficient guidance or instruction to one of ordinary skill in the art in selecting Vitamin C and manganese from the large number of excipients disclosed by Gellman, and to combine them in the manner proposed by the Examiner.
Burshtein discloses magnesium stearate AND NOT manganese stearate. Magnesium stearate and manganese stearate are different compounds. Accordingly, one of ordinary skill in the art would not have been motivated to combine the teachings of Gellman and Burshtein. Aungst generally teaches the use of absorption enhancers to improve absorption of a pharmacological drug. EFSA is just a scientific opinion based on the safety of manganese ascorbate, manganese aspartate, manganese bisglycinate and manganese pidolate as sources of manganese for nutritional purposes added to food supplements. EFSA provides no guidance regarding the use of manganese gluconate or any of its salts as claimed in the present invention. Therefore, one of ordinary skill in the art would not have referred to EFSA while preparing any composition of PTH analogues.
Applicant’s arguments have been fully considered but not found persuasive. Applicants argue that Gellman does not teach or suggest the claimed metal-containing compounds and reducing agents and that Gellman relates only to peptide synthesis rather than pharmaceutical formulation. This is not persuasive. Although Gellman describes methods of synthesizing PTH analogs, Gellman also expressly claims pharmaceutical formulations comprising a PTH receptor agonist effective amount of a PTH analog in combination with a pharmaceutically acceptable carrier (see claims 20-21). Gellman further teaches oral administration of such compositions (see paragraph 0081) and identifies common excipients such as lactose, manganese and vitamin C that may be include in the compositions containing the PTH analogs (see paragraphs 0071, 0079). Accordingly, Gellman is the same field of endeavor, formulation of PTH analogs, and is reasonably pertinent to the problem faced by applicant, satisfying both prongs of the analogous art test under MPEP 2141.01 (a).
Applicants additionally argue that manganese and vitamin C in Gellman are disclosed in “nutritional compositions”, not pharmaceutical compositions. The distinction drawn by applicant is no persuasive. The compositions disclosed in Gellman, whether described as nutritional or pharmaceutical, nonetheless contain the same active agent required by the present claims, a PTH analog, together with excipients suitable for oral administration. Gellman therefore teaches compatibility of manganese, vitamins C with PTH analogs. Under KSR v. Teleflex and MPEP 2143(I)(B), a person of ordinary skill may apply known excipients in closely related contexts where the perform predictable functions. Manganese salts are widely known as nutritional sources of Manganese in oral formulations and ascorbic acid is well known reducing agent routinely used to limit oxidation. Their known functional roles would have motivated a person of ordinary skill to incorporate them into the claimed composition with a reasonable expectation of success.
Applicants further contend that Gellman discloses a lengthy list of ingredients and therefore does not instruct a person of ordinary skill in the art to select manganese and vitamin C together. However, the law does not require a reference to direct a person of ordinary skill in the art to the exact combination used in the claims. Under KSR, obviousness may be found where a person of ordinary skill in the art selects from a finite number of identified, predictable options to achieve a predictable result. Manganese salts and vitamin C are not arbitrary choices; both are specifically disclosed by Gellman as suitable excipients for compositions containing PTH analogs, and each performs a conventional, well-understood role. Selecting such known excipients for their established functions constitutes the type of routine optimization that is considered obvious under KSR and MPEP §2143.
Applicants argue that Aungst only generally teaches absorption enhancers and does not relate to PTH analogs. This argument is also not persuasive. Aungst provides explicit motivation to include an absorption enhancer because Aungst teaches that such enhancers are functional excipients routinely used to improve absorption of pharmacologically active drugs (Aungst, abstract; Table III). Improving the oral uptake of peptides is a well-recognized formulation challenge, and Aungst identifies suitable permeation enhancers, including fatty acids and salts, that a person of ordinary skill would have considered for use in any oral peptide formulation, including a PTH analog.
Applicants next argue that EFSA is merely a scientific opinion and would not have been consulted in preparing pharmaceutical compositions. This is not persuasive. EFSA teaches that manganese gluconate, manganese chloride, manganese sulfate, and related salts are safe, orally acceptable metal sources (GRAS) and describes their permitted use in food and supplements. A POSA formulating an orally administered composition routinely considers excipient safety and acceptability, including GRAS listings and regulatory guidance. EFSA therefore provides relevant information confirming that the manganese salts disclosed by Gellman are appropriate and safe for oral administration, supporting their use in the claimed composition.
Applicants further argue that Burshtein teaches magnesium stearate rather than manganese stearate and therefore is inapplicable. This mischaracterizes the reliance on Burshtein. Burshtein is cited not for teaching a specific manganese salt but for teaching the general formulation principle of physically separating a peptide active agent from reactive excipients to improve stability, through coated particles, layered structures, or other compartmentalized dosage forms. Physical separation is a widely used formulation strategy, particularly for peptides, which are susceptible to oxidative degradation. A person of ordinary skill in the art would have reasonably applied this principle to the oral PTH compositions of Gellman to ensure stability consistent with KSR and MPEP §2143.
Finally, applicants argue that a person of ordinary skill in the art would not combine Gellman, Aungst, and EFSA. This argument is not persuasive. Each reference addresses the same goal, preparing orally administered compositions, and provides complementary teachings. Gellman provides PTH analogs and compatible excipients, Aungst provides absorption enhancers to improve uptake, and EFSA teaches acceptable forms of manganese salts suitable for oral ingestion. Combining known elements for their predictable functions to improve an oral formulation is within KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP 2143, Examples of Rationales).. Accordingly, applicants’ arguments do not overcome the prima facie case of obviousness.
Claim(s) 9, 12, 14 remain rejected under 35 U.S.C. 103 as being unpatentable over Gellman (US20140378382, cited previously) in view of Aungst (The AAPS Journal, Vol. 14, No. 1, March 2012) and EFSA (The EFSA Journal (2009) 1114, 1-23) as applied to claims 9, 12 and 15-16, in further view of SwallowingDifficulties (https://www.swallowingdifficulties.com/healthcare-professionals/prescribing-different-formulations/different-coatings, “Different coatings”, posted online 2009) *All references cited previously.
The teachings of Gellman in view of Aungst and EFSA are described above. The combined teachings are silent to enteric coating of the formulation.
However, SwallowingDifficulties teaches that “If a tablet is described as having an ‘enteric coating’ (e/c) or ‘gastro-resistant’, it means that there is a coating which is designed to hold the tablet together when in the stomach. This clever science relies on the fact that the stomach is acid and the intestines, where food goes after the stomach, are not. The coating is designed to hold together in acid conditions and break down in non-acid conditions and therefore release the drug in the intestines. There are three reasons for putting such a coating on a tablet or capsule ingredient: To protect the stomach from the drug, to protect the drug from the stomach to release the drug after the stomach e.g. in the intestines” (see “Enteric Coating”).
It would have been obvious before the effective filing date of the claimed invention to enteric coat the formulation of Gellman in view of Aungst and EFSA. One of ordinary skill in the art would have been motivated to do so to protect the tables from the acid in the stomach to obtain optimal absorption of the drug in the intestines. There is a reasonable expectation of success given that enteric coating drugs for oral administration is routine to protect from the acidic environment in the stomach.
Response to Applicant’s Arguments
Applicants reiterate the aforementioned arguments with respect to the instant rejection. The Office’s rebuttal of these arguments remains the same and is incorporated herein by reference.
Claim(s) 9, 12-13 remain rejected under 35 U.S.C. 103 as being unpatentable over Gellman (US20140378382, cited previously) in view of Aungst (The AAPS Journal, Vol. 14, No. 1, March 2012) and EFSA (The EFSA Journal (2009) 1114, 1-23) as applied to claims 9 and 12, in further view of Burshtein (WO2018033927, cited in Applicant’s IDS) *All references cited previously.
The teachings of Gellman in view of Aungst and EFSA are described above. The combined teachings are silent to wherein the PTH analogue and the degradation agent are administered separately.
However, Burshtein teaches oral pharmaceutical compositions comprising a therapeutically effective agent such as a PTH analogue and absorption enhancer that are administering separately (see abstract). Burshtein teaches “Multi-unit formulations of 1.5 mg recombinant PTH(l-34) (teriparatide) were prepared which consisted of 2 tablets of 0.75 mg or 3 tablets of 0.5 mg or 3 tablets. 1 tablet of 1.5 mg teriparatide served as a control dosage. Each tablet was composed of PTH(l-34) (in the indicated amount), SNAC (sodium 8-N-(2-hydroxybenzoyl) aminocaprylate), soybean trypsin inhibitor (SBTI) and a small amount of manganese stearate, and all of the tested tablets were prepared from the same formulation blend”. Burshtein teaches that “These results indicate that the presence of multiple units in the formulation increases peptide bioavailability upon oral administration.”
It would have been obvious before the effective filing date of the claimed invention to have multi units of the formulation (which each unit would have separated forms) for treating hypoparathyroidism. One of ordinary skill in the art would have been motivated to do so to increases peptide bioavailability upon oral administration. There is a reasonable expectation of success given that Burshtein shows that multiple separate units are advantageous for bioavailability upon oral administration with PTH analogues.
Response to Applicant’s Arguments
Applicants reiterate the aforementioned arguments with respect to the instant rejection. The Office’s rebuttal of these arguments remains the same and is incorporated herein by reference.
Claim(s) 9, 12, 16 remain rejected under 35 U.S.C. 103 as being unpatentable over Gellman (US20140378382) in view of Aungst (The AAPS Journal, Vol. 14, No. 1, March 2012) and EFSA (The EFSA Journal (2009) 1114, 1-23) as applied to claims 9 and 12 above, in further view of FOGER (US20180280481, cited previously).
The teachings of Gellman in view of Aungst and EFSA are described in the above rejection. The combined references are silent to wherein the absorption enhancer is one of solutol, labrasol or vitamin E.
FOGER teaches a peptide drug complex comprising a metal salt complex (see claim 1) and ascorbic acid as a reducing agent (see paragraph 0057) and also an absorption enhancer (See paragraph 0048). FOGER teaches many different absorption enhancers including solutol and labrosol (see paragraph 0075, claim 27, Example 1).
It would have been obvious before the effective filing date of the claimed invention to include the absorption enhancer solutol or labrasol to improve the absorption of the PTH analog. One of ordinary skill in the art would have been motivated to do so to enhance absorption of the drug which in turn would allow for greater therapeutic effectiveness. There is a reasonable expectation of success given that absorption enhancers including both labrasol and solutol are commonly used excipients used in oral formulations to improve uptake of peptides as taught by FOGER. Furthermore, it would have been obvious to try use of either labrasol or solutol as an absorption enhancer as each are known in the art for that purpose (see MPEP 2143 (1)(E)). A person of ordinary skill in the art would have found it obvious to try known absorption enhancers from the finite list disclosed in FOGER. Labrasol, solutol and vitamin E fall within these predictable absorption enhancer classes, and their use would be expected to improve peptide absorption, making the selection of any one of these obvious to try.
Response to Applicant’s Arguments
Applicants reiterate the aforementioned arguments with respect to the instant rejection. The Office’s rebuttal of these arguments remains the same and is incorporated herein by reference.
New Objection
Claim 9 is objected to for the following informality: the limitation “a” should be inserted following “comprising” in line 1 and after “effective amount of” in line 2.
New Rejections
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 9, 13-14, 16 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 9 claims “….wherein said at least one metal containing compound is selected from the group consisting of vanadium (V) oxide, sodium vanadate, vanadium sulfate, vanadyl sulfate, vanadium biguanide, bis(maltolato)oxavanadium (IV), vanadium acetate, vanadyl picolinate, vanadyl citrate, chromium picolinate, chromium polynicotinate, chromium nicotinate, chromium chloride, chromium acetate, potassium permanganate, manganese gluconate, and manganese chloride, in any form including salts or complex thereof….”It is unclear whether “an any form” is intended to cover all forms of the listed compounds (e.g. free form, hydrates, salts, complexes), with salts/complexes being examples or whether the claimed is intended to be limited to salts or complexes only. Because the phrase reasonably supports more than on interpretation, the metes and bounds of the claim cannot be determined. Therefor the claim is indefinite. See MPEP § 2173.05(d).
Claims 13-14 and 16 are also rejected due to their dependence on claim 9 and not clarifying this point of confusion.
Claim 16 contains the trademark/trade name labrasol. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe labrasol and, accordingly, the identification/description is indefinite.
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 9, 12-14, 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of US Patent No. 12208118 (reference application) in view of Gellman (US20140378382), Swallowing Difficulties (https://www.swallowingdifficulties.com/healthcare-professionals/prescribing-different-formulations/different-coatings, “Different coatings”, posted online 2009) and FOGER (US20180280481, cited previously).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “An oral pharmaceutical composition comprising therapeutically effective amount of PTH analog selected from the group consisting of teriparatide and abaloparatide, wherein said composition upon oral administration provides relative bioavailability of at least 0.5% compared to subcutaneous administration, wherein said composition further comprises at least one degradation preventing agent, and said at least one degradation preventing agent comprises a combination of at least one metal containing compound and at least one reducing agent, wherein said at least one metal containing compound is selected from the group consisting of vanadium (V) oxide, sodium vanadate, vanadium sulfate, vanadyl sulfate, vanadium biguanide, bis(maltolato)oxavanadium (IV), vanadium acetate, vanadyl picolinate, vanadyl citrate, chromium picolinate, chromium polynicotinate, chromium nicotinate, chromium chloride, chromium acetate, potassium permanganate, manganese gluconate, and manganese chloride, in any form including salts or complex thereof, wherein said at least one reducing agent is selected from the group consisting of ascorbic acid, reduced glutathione, cysteine, reducing sugar, glyceraldehyde, a-tocopherol, vitamin A, a- lipoic acid, dihydro-a-lipoic acid, glucose, galactose, lactose, maltose, thiol bearing compound, a thiomer and pharmaceutically acceptable salts thereof, and wherein said composition further comprises at least one absorption enhancer.” The instant solutol (claim 16); enteric coated (claim 14); physically separated form (claim 13); manganese gluconate (claim 12).
US Patent No. 12208118 claims “ A pharmaceutical composition comprising: a pharmaceutically effective amount of at least one peptide; and a pharmaceutically acceptable amount of a combination of: (a) at least one metal in the form of any of, or a combination of, a salt thereof and a complex thereof; and (b) at least one reducing agent,
wherein, said at least one metal is selected from any of, or a combination of: vanadium (V) oxide, sodium vanadate, vanadium sulfate, potassium permanganate, manganese gluconate, chromium picolinate and chromium chloride, and wherein said pharmaceutical composition further comprises at least one absorption enhancer” (see claim 1). US Patent No. 12208118 further claims parathyroid hormone in a list of potential peptides (see claim 9); wherein said at least one peptide and said at least one metal in the form of any of, or a combination of, a salt thereof and a complex thereof are present in physically separated form in said pharmaceutical composition (claim 10); wherein said pharmaceutical composition is present in the form of any of a capsule-in-capsule and a tablet-in-capsule (claim 12); wherein said at least one reducing agent is selected from any of, or a combination of, ascorbic acid, reduced glutathione, cysteine, uric acid, reducing sugar, glyceraldehyde, α-tocopherol, vitamin A, α-lipoic acid, dihydro-α-lipoic acid, glucose, galactose, lactose, maltose, thiol-bearing compound, a thiomer and pharmaceutically acceptable salts thereof (claim 13).
US Patent No. 12208118 is silent to the absorption enhancer of labrasol, solutol or vitamin E, enteric coated forms and specifically abaloparatide.
However, Regarding absorption enhancers, FOGER teaches a peptide drug complex comprising a metal salt complex (see claim 1) and ascorbic acid as a reducing agent (see paragraph 0057) and also an absorption enhancer (See paragraph 0048). FOGER teaches many different absorption enhancers including solutol and labrosol (see paragraph 0075, claim 27, Example 1).
It would have been obvious before the effective filing date of the claimed invention to include the absorption enhancer solutol or labrasol to improve the absorption of the peptide. One of ordinary skill in the art would have been motivated to do so to enhance absorption of the drug which in turn would allow for greater therapeutic effectiveness. There is a reasonable expectation of success given that absorption enhancers including both labrasol and solutol are commonly used excipients used in oral formulations to improve uptake of peptides as taught by FOGER. Furthermore, it would have been obvious to try use of either labrasol or solutol as an absorption enhancer as each are known in the art for that purpose (see MPEP 2143 (1)(E)). A person of ordinary skill in the art would have found it obvious to try known absorption enhancers from the finite list disclosed in FOGER. Labrasol, solutol and vitamin E fall within these predictable absorption enhancer classes, and their use would be expected to improve peptide absorption, making the selection of any one of these obvious to try.
Regarding enteric coating (instant claim 14), SwallowingDifficulties teaches that “If a tablet is described as having an ‘enteric coating’ (e/c) or ‘gastro-resistant’, it means that there is a coating which is designed to hold the tablet together when in the stomach. This clever science relies on the fact that the stomach is acid and the intestines, where food goes after the stomach, are not. The coating is designed to hold together in acid conditions and break down in non-acid conditions and therefore release the drug in the intestines. There are three reasons for putting such a coating on a tablet or capsule ingredient: To protect the stomach from the drug, to protect the drug from the stomach to release the drug after the stomach e.g. in the intestines” (see “Enteric Coating”).
It would have been obvious before the effective filing date of the claimed invention to enteric coat the formulation of US Patent No. ‘118 One of ordinary skill in the art would have been motivated to do so to protect the tables from the acid in the stomach to obtain optimal absorption of the drug in the intestines. There is a reasonable expectation of success given that enteric coating drugs for oral administration is routine to protect from the acidic environment in the stomach.
Regarding specifically abaloparatide or teriparatide, Gellman teaches that abaloparatide and teriparatide are well known predictable variants of parathyroid hormone with similar activity. A person of ordinary skill would have therefore would have had a reasonable expectation of success in substituting PTH analog for PTH in the composition in the claimed composition of US Patent. No. ‘118. Accordingly, the presently claimed subject matter constitutes an obvious variant of the earlier claimed invention and is unpatentable under the judicially created doctrine on nonstatutory obviousness type double patenting.
Conclusion
No claims are allowed.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654