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 .
Status of Action/Claims
Receipt of Remarks/Amendments filed on 12/30/2025 is acknowledged. Claims 1, 5, 8-10, 12 and 15 are currently pending and are presented for examination on the merits for patentability.
Rejection(s) not reiterated from the previous Office Action are hereby withdrawn. The following rejections are either reiterated or newly applied. They constitute the complete set of rejections presently being applied to the instant application.
Withdrawn Rejection(s)/Objection(s)
The previous claim objections and rejections under 112(d) have been withdrawn due to appropriate claim amendments.
New/Maintained Claim Objections/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 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) 1, 5, 8-10, 12 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hall et al. (US20060204585) and further in view of EP0813424 (from IDS) and Hepburn et al. (US20050220870).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Hall teaches and specifically claims pharmaceutical formulations comprising PPIs and antacids, wherein the antacids are selected from magnesium hydroxide and magnesium oxide, etc. and wherein the PPIs, e.g. lansoprazole are used in 30 mg to the magnesium oxide in amounts of 151 mg (See Example 2G). Hall teaches example 2G which also teaches lansoprazole present in 30 mg and magnesium hydroxide which is present in amounts of 500 mg of magnesium hydroxide and this equates to a ratio of 16.67:1 (500/30= 16.67:1 ) (See example 2G). Hall teaches wherein the composition further comprises a disintegrant, e.g. croscarmellose sodium (see example 2G).
With respect to the instantly claimed recitation wherein the composition does not comprise sodium bicarbonate and calcium carbonate as an antacid, Hall teaches wherein the antacid is selected from sodium bicarbonate, sodium carbonate, calcium carbonate, magnesium oxide, potassium bicarbonate, magnesium hydroxide, magnesium carbonate, aluminum hydroxide, and mixtures thereof (claim 15). Thus, Hall teaches that the compositions can include only magnesium hydroxide or magnesium oxide and does not require sodium bicarbonate or calcium carbonate.
Hall’s claims do not require or claim an enteric coating and as such an enteric coating is not claimed/included or required by Hall’s formulations (See claims). Hall teaches examples which do not comprise esomeprazole as the PPI. However, Hall expressly teaches that the PPI can be esomeprazole (claims; [0085]; [0092]; [0193]; [0196];).
Hall teaches multiple examples wherein the PPIs are all used in amounts of 20-40mg (see examples) and wherein magnesium hydroxide is used in amounts of 500 mg (e.g. Example 2G), and wherein the antacids are known to be used in amounts of between 200 and 3500 mg ([0123]; claims).
Hall teaches wherein their formulations can comprise croscarmellose sodium/crosslinked sodium carboxymethyl cellulose and/or wherein the binder can be hydroxypropyl cellulose ([0052]; [0076]; [0179]).
Ascertainment of the difference between prior art and the claims
(MPEP 2141.02)
Hall does not teach wherein their tablet is a bilayer tablet. However, this deficiency in Hall is addressed by EP0813424 and Hepburn.
EP0813424 teaches bilayer tablets comprising a layer with a PPI, and a secondary/second layer comprising an antacid, specifically magnesium based antacid agents such as magnesium hydroxide are preferred antacid agents ([0018]; abstract; figure 2;).
With respect to claim 12, EP0813424 teaches that the claimed HPC (hydroxypropyl cellulose) can be used as a binder for the bilayer tablets and as such the primary or secondary layer can further comprise hydroxypropyl cellulose as a binder ([0039]).
Hepburn teaches that it was known that combining PPIs with antacids in non-enterically coated tablet formulations wherein upon administration, the composition contacts the gastric fluid of the stomach and increases the gastric fluid pH of the stomach to a pH that substantially prevents or inhibits acid degradation of the proton pump inhibiting agent in the gastric fluid and allows a measurable serum concentration of the proton pump inhibiting agent to be absorbed into the blood serum of the subject and wherein dissolution of the PPI is improved and wherein preferred antacid agents include the claimed magnesium hydroxide and magnesium carbonate and wherein the PPIs include esomeprazole, lansoprazole and salts thereof, e.g. esomeprazole magnesium (See abstract; [0002]; claims (all claims); [0017]; [0019-0020]; [0150]; claim 48 (not enteric-coated); [0229]).
Finding of prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
It would have been obvious to formulate the pharmaceutical formulation of Hall as a bilayer tablet without an enteric coating because Hall teaches that an enteric coating is not necessary for pharmaceutical formulations comprising a PPI and the claimed antacids. However, it would have been obvious to formulate the PPI in one layer and the antacid as a second layer in a bilayer tablet because EP0813424 teaches that bilayer formulations of PPI in one layer and antacids in another layer were known in the art to be stable and effective and as such it would be obvious to formulate the composition/formulation of Hall as a bilayer tablet since this is a known formulation type for the claimed active agents and it was known to separate the claimed active agents in separate layers for effective oral dosing/delivery. Further one of ordinary skill in the art would be motivated to optimize the ratios and amounts of antacid to PPI in the tablets to the claimed ratios as are broadly taught by Hall because Hepburn teaches that it was known that combining PPIs with antacids in non-enterically coated tablet formulations wherein upon administration, the composition contacts the gastric fluid of the stomach and increases the gastric fluid pH of the stomach to a pH that substantially prevents or inhibits acid degradation of the proton pump inhibiting agent in the gastric fluid and allows a measurable serum concentration of the proton pump inhibiting agent to be absorbed into the blood serum of the subject and wherein dissolution of the PPI is improved.
It also would have been obvious to use the claimed hydroxypropyl cellulose as a binder or the PPI and/or the antacid layer when forming the claimed bilayer drug formulation as taught by the combination of Hall and EP0813424 because EP0813424 teaches that this is an effective binder for formulating bilayer tablets comprising PPls and the claimed antacids and Hall teaches that it is an effective binder for formulations comprising both the claimed PPIs and antacids in tablet form and as such it would have been obvious to select known effective binders for formulating the claimed PPls and antacid active agents into bilayer tablets in order to formulate the same drugs into the claimed bilayer tablets in order to form additional effective PPI/antacid bilayer tablets as taught by the combined references.
Regarding claim 15, it would have been obvious to one of ordinary skill in the art to optimize the formulation taught by the combined prior art to provide the claimed dissolution profile because it is known in the art to optimize pharmaceutical formulations to have the desired dissolution profiles/rates. Thus, one of ordinary skill in the art would optimize the binders, amounts of PPls, antacids, and other formulation auxiliaries to provide the desired dissolution profile/rates as this is something that one of ordinary skill in the art routinely does. Especially since the combination of the prior art teaches the claimed components and carriers/binders were known in the art as is discussed above, and because Hepburn teaches that it was known that combining PPIs with antacids in non-enterically coated tablet formulations wherein upon administration, the composition contacts the gastric fluid of the stomach and increases the gastric fluid pH of the stomach to a pH that substantially prevents or inhibits acid degradation of the proton pump inhibiting agent in the gastric fluid and allows a measurable serum concentration of the proton pump inhibiting agent to be absorbed into the blood serum of the subject and wherein dissolution of the PPI is improved. Thus, it would be obvious to optimize the amounts of antacid to PPIs to achieve the desired dissolution profile/rates because the addition of appropriate amounts of antacids into PPI tablet formulations allows for the composition, i.e. the antacid in the composition, to contact the gastric fluid of the stomach and increase the gastric fluid pH of the stomach to a pH that substantially prevents or inhibits acid degradation of the proton pump inhibiting agent in the gastric fluid and allows a measurable serum concentration of the proton pump inhibiting agent to be absorbed into the blood serum of the subject and wherein dissolution of the PPI is improved. Thus, it would be obvious to select the antacid and PPI combination which allows for improved dissolution and absorption of the PPI while also leading to less/no degradation of the PPI in/by the gastric fluid in the stomach. Thereby leading to more effective inhibition of the proton pumps by the PPI, etc.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the above claims would have been obvious to one of ordinary skill in the art within the meaning of 35 USC 103(a).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 5, 8-10, 12 and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 18/004317 in view of Hall (cited above) and EP0813424. ‘317 and the instant application both claim double layered and/or bilayered pharmaceutical formulations comprising one layer which contains PPIs, specifically the same PPIs instantly claimed combined and a second layer comprising the same antacids instantly claimed, and the same lubricant, etc. which are instantly claimed and wherein none of the claims refer to an enteric coating and as such would read on wherein an enteric coating agent is not included and ‘317 teaches wherein their tablets also comprise the claimed binders/additives, e.g. HPC (hydroxypropyl cellulose), etc. and wherein the formulation can have the PPI in a first layer and the antacid in the second layer, and wherein the tablet has the exact same dissolution profile as is instantly claimed. ‘317 also does not require inclusion of sodium bicarbonate or calcium carbonate. ‘317 does not teach wherein the antacids (MgO and Mg(OH)2) are present in the claimed amounts and/or ratios which are instantly claimed. These deficiencies in ‘317 are addressed by Hall.
Hall teaches examples which do not comprise esomeprazole as the PPI. However, Hall expressly teaches that the PPI can be esomeprazole (claims; [0085]; [0092]; [0193]; [0196];). Hall teaches other examples which comprise the PPIs in the claimed ratios, e.g. Example 2G which teaches the PPI lansoprazole being used in 30 mg to the magnesium oxide in amounts of 151 mg (See Example 2G) which reads on/anticipates the claimed ratio of at least 5 parts magnesium oxide to 1 part PPI claimed in claim 7.
Hall teaches example 2G which also teaches lansoprazole present in 30 mg and magnesium hydroxide which is present in amounts of 500 mg of magnesium hydroxide and (500/30= 16.67:1 ) which means that the Mg(OH)2 in an amount of 6.25 parts by weight or more per 1 part by weight of PPI (See example 2G).
Hall teaches multiple examples wherein the PPIs are all used in amounts of 20-40mg (see examples) and wherein magnesium hydroxide is used in amounts of 500 mg (e.g. Example 2G), and wherein the antacids are known to be used in amounts of between 200 and 3500 mg ([0123]; claims).
Hall teaches wherein their formulations can comprise croscarmellose sodium/crosslinked sodium carboxymethyl cellulose and/or wherein the binder can be hydroxypropyl cellulose ([0052]; [0076]; [0179]).
‘317 does not teach wherein the tablet is a bilayer tablet. However, EP0813424 cures this deficiency. EP0813424 teaches that it is known to formulate two layers such as those of ‘317 wherein 1 layer comprises PPI and the other layer comprises antacid(s) as a bilayer tablet (([0018]; abstract; figure 2; [0039]).
It would have been obvious to one of ordinary skill in the art to have formulated the PPI and antacid two layered tablet formulation of ‘317 as a bilayer tablet as this is a well-known way to formulate such layered tablets, and it would have been obvious to use the PPIs, specifically esomeprazole in the claimed amounts with the magnesium oxide and/or magnesium hydroxide in the claimed amounts and/or ratios claimed because Hall teaches that these ratios of magnesium oxide and magnesium hydroxide were known to be effective when formulating tablets containing other PPIs, such as the claimed lansoprazole and as such would be a good starting point for formulation/optimizing the claimed esomeprazole formulations. Thus, one of ordinary skill in the art would have concluded that the instantly claimed inventions are obvious when taken in view of copending 18/004317 in view of Hall (cited above) and EP0813424.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 5, 8-10, 12 and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of copending Application No. 17794178 in view of in view of EP0813424. ‘178 and the instant application both claim pharmaceutical formulations comprising PPIs, specifically the same PPIs instantly claimed combined with the same antacids instantly claimed, and the same disintegrants, etc. which are instantly claimed and wherein none of the claims refer to an enteric coating and as such would read on wherein an enteric coating agent is not included and ‘178 teaches wherein their tablets also comprise the claimed binders/additives, e.g. HPC (hydroxypropyl cellulose), and wherein the formulation can have the PPI in a first layer and the antacid in the second layer, i.e. as a bilayered tablet, and wherein the tablet has an overlapping dissolution profile to that instantly claimed. ‘178 also does not require sodium bicarbonate or calcium carbonate. ‘178 does not teach wherein the tablet is specifically a bilayer tablet or wherein the antacids (MgO and Mg(OH)2) are present in the claimed amounts and/or ratios which are instantly claimed with esomeprazole and/or other PPIs as claimed. However, these deficiencies are addressed by Hall and EP0813424.
Hall teaches examples which do not comprise esomeprazole as the PPI. However, Hall expressly teaches that the PPI can be esomeprazole (claims; [0085]; [0092]; [0193]; [0196];). Hall teaches other examples which comprise the PPIs in the claimed ratios, e.g. Example 2G which teaches the PPI lansoprazole being used in 30 mg to the magnesium oxide in amounts of 151 mg (See Example 2G) which reads on/anticipates the claimed ratio of at least 5 parts magnesium oxide to 1 part PPI claimed in claim 7.
Hall teaches example 2G which also teaches lansoprazole present in 30 mg and magnesium hydroxide which is present in amounts of 500 mg of magnesium hydroxide and (500/30= 16.67:1) which means that the Mg(OH)2 in an amount of 6.25 parts by weight or more per 1 part by weight of PPI (See example 2G).
Hall teaches multiple examples wherein the PPIs are all used in amounts of 20-40mg (see examples) and wherein magnesium hydroxide is used in amounts of 500 mg (e.g. Example 2G), and wherein the antacids are known to be used in amounts of between 200 and 3500 mg ([0123]; claims).
Hall teaches wherein their formulations can comprise croscarmellose sodium/crosslinked sodium carboxymethyl cellulose and/or wherein the binder can be hydroxypropyl cellulose ([0052]; [0076]; [0179]).
‘178 does not teach wherein the tablet is a bilayer tablet. However, EP0813424 cures this deficiency. EP0813424 teaches that it is known to formulate two layers such as those of ‘178 wherein 1 layer comprises PPI and the other layer comprises antacid(s) as a bilayer tablet (([0018]; abstract; figure 2; [0039]).
It would have been obvious to one of ordinary skill in the art to have formulated the PPI and antacid two layered tablet formulation of ‘178 as a bilayer tablet as this is a well-known way to formulate such two layered tablets, and it would have been obvious to use the PPIs, specifically esomeprazole in the claimed amounts with the magnesium oxide and/or magnesium hydroxide in the claimed amounts and/or ratios claimed because Hall teaches that these ratios of magnesium oxide and magnesium hydroxide were known to be effective when formulating tablets containing other PPIs, such as the claimed lansoprazole and as such would be a good starting point for formulation/optimizing the claimed esomeprazole formulations. Thus, one of ordinary skill in the art would have concluded that the instantly claimed inventions are obvious when taken in view of copending 17794178 in view of Hall (cited above) and EP0813424.
Response to Arguments
Applicant's arguments filed 12/30/2025 have been fully considered but they are not persuasive.
Applicant argued Hall utilizes dry coating or microencapsulation of the proton pump inhibitor particles and in contrast, the claimed bilayer tablet composition utilizes a macroscopic bilayer tablet structure. Esomeprazole is not mixed with an antacids and instead the secondary antacid layer is designed to rapidly neutralize the gastric acid in the immediate environment of the tablet upon ingestion. One skilled in the would not find it obvious to move from a particle coating strategy to a macroscopic layer neutralization strategy, while excluding sodium bicarbonate.
In response, Hall teaches antacid for neutralizing gastric acid (e.g., para 005; 0110; 0128; 0131; 0187) and EP0813424 also teaches antacids agents work through neutralization of gastric acid. It would have been obvious to formulate the PPI in one layer and the antacid as a second layer in a bilayer tablet because EP0813424 teaches that bilayer formulations of PPI in one layer and antacids in another layer were known in the art to be stable and effective and as such it would be obvious to formulate the composition/formulation of Hall as a bilayer tablet since this is a known formulation type for the claimed active agents and it was known to separate the claimed active agents in separate layers for effective oral dosing/delivery. Thus, Hall teaching dry coating or microencapsulation of the proton pump inhibitor particles does not teach away from making a bilayer tablet which comprises a layer of PPI and another layer of antacid. Regarding excluding sodium bicarbonate, Hall teaches wherein the antacid is selected from sodium bicarbonate, sodium carbonate, calcium carbonate, magnesium oxide, potassium bicarbonate, magnesium hydroxide, magnesium carbonate, aluminum hydroxide, and mixtures thereof (claim 15). Thus, Hall teaches that the compositions can include only magnesium hydroxide or magnesium oxide and does not require sodium bicarbonate or calcium carbonate.
Applicant argued that amended claims exclude both sodium bicarbonate and calcium carbonate and the exclusion of these carbonates is critical. Formulations with sodium bicarbonate or calcium carbonate showed significantly lower dissolution rates compared to the magnesium based bilayer tablets of present claims.
In response, regarding excluding sodium bicarbonate and calcium carbonate, Hall teaches wherein the antacid is selected from sodium bicarbonate, sodium carbonate, calcium carbonate, magnesium oxide, potassium bicarbonate, magnesium hydroxide, magnesium carbonate, aluminum hydroxide, and mixtures thereof (claim 15). Thus, Hall teaches that the compositions can include only magnesium hydroxide or magnesium oxide and does not require sodium bicarbonate or calcium carbonate. “Disclosed examples and preferred embodiments do not constitute a teaching away from the broader disclosure or non-preferred embodiment.” In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). MPEP 2123.
Regarding applicant’s argument of criticality of excluding the carbonates and sodium bicarbonate or calcium carbonate showing significantly lower dissolution rates compared to the magnesium based bilayer tablets, the examiner again respectfully draws applicant’s attention to Schaefer et al. (Neutralization of acid in the rumen by magnesium oxide and magnesium carbonate, Journal of Dairy Science, vol. 65, no. 5, 1982) and specifically, Schaefer et al. teaches that magnesium oxides capacity to neutralize acid in the rumen is at least twice as compared to calcium carbonate, sodium bicarbonate and magnesium carbonate (see: Results and Discussion). Gurol et al. (US6066342A; May 23, 2000) discloses that magnesium hydroxide is a stronger acid neutralizing agent as compared to calcium carbonate (see e.g. col. 2, line 1-11; col. 12, line 16-30; entire document). Darwin (Journal of Advanced Veterinary and Animal Research., 6(1): 100-107, March 2019) discloses using magnesium hydroxide and sodium bicarbonate to prevent lactic acid build up in the rumen culture. Sodium bicarbonate is widely known and used for neutralizing acid accumulation in the rumen. Results showed magnesium hydroxide could prevent lactic acid accumulation while sodium bicarbonate did not prevent acidosis and had lactic acid accumulation. (see e.g., Results; Conclusion; Discussion; Entire Document). Hall teaches proton pump inhibitors are susceptible to acid degradation and, as such, are rapidly destroyed as pH falls to an acidic level. The antacid when formulated or delivered with a PPI agent functions to substantially inhibit acid degradation of the PPI by gastrointestinal fluid. (see para 0005; 0037; 0113). As discussed supra, Hepburn also teaches that it was known that combining PPIs with antacids in non-enterically coated tablet formulations wherein upon administration, the composition contacts the gastric fluid of the stomach and increases the gastric fluid pH of the stomach to a pH that substantially prevents or inhibits acid degradation of the proton pump inhibiting agent in the gastric fluid and allows a measurable serum concentration of the proton pump inhibiting agent to be absorbed into the blood serum of the subject and wherein dissolution of the PPI is improved. The prior art recognizes that addition of antacid to formulation comprising PPI improves the dissolution of PPI and prevents its degradation from the acid in the stomach. Schaefer, Gurol and Darwin teach magnesium oxide and magnesium hydroxide having greater acid neutralization capacity as compared to sodium bicarbonate and calcium carbonate, and therefore, it would have been obvious to one skilled in the art to expect improved dissolution and lower degradation of PPI with the use of magnesium oxide or magnesium hydroxide as compared to sodium bicarbonate or calcium carbonate. Thus, applicant’s argument of magnesium oxide or magnesium hydroxide providing superior acid degradation inhibition and improved dissolution of PPI compared to composition containing sodium bicarbonate or calcium carbonate does not appear to be an unexpected result based on what was known in the art.
Applicant argued Hall discloses only compositions in which the PPI is lansoprazole, and it would not be obvious to predict from Hall the acid degradation prevention effect in a case where esomeprazole is included as the PPI. Applicant further argued the claimed weight ratio of magnesium hydroxide or magnesium oxide exhibit superior acid degradation prevention and stability effects. Applicant pointed to the examples in the specification to argue that the claimed weight amount/ratio are critical.
In response, while Hall does not exemplify using esomeprazole, Hall expressly teaches that the PPI can be esomeprazole (claims; [0085]; [0092]; [0193]; [0196];). “Disclosed examples and preferred embodiments do not constitute a teaching away from the broader disclosure or non-preferred embodiment.” In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). MPEP 2123. Further, as discussed supra, Schaefer, Gurol and Darwin teach magnesium oxide and magnesium hydroxide having greater acid neutralization capacity as compared to sodium bicarbonate and calcium carbonate. Hall teaches proton pump inhibitors are susceptible to acid degradation and, as such, are rapidly destroyed as pH falls to an acidic level. The antacid when formulated or delivered with a PPI agent functions to substantially inhibit acid degradation of the PPI by gastrointestinal fluid. (see para 0005; 0037; 0113). As discussed supra, Hepburn also teaches that it was known that combining PPIs with antacids in non-enterically coated tablet formulations wherein upon administration, the composition contacts the gastric fluid of the stomach and increases the gastric fluid pH of the stomach to a pH that substantially prevents or inhibits acid degradation of the proton pump inhibiting agent in the gastric fluid and allows a measurable serum concentration of the proton pump inhibiting agent to be absorbed into the blood serum of the subject and wherein dissolution of the PPI is improved. The prior art recognizes that addition of antacid to formulation comprising PPI improves the dissolution of PPI and prevents its degradation from the acid in the stomach. Therefore, it would have been to one skilled in the art that a higher amount of the antacid would have greater capacity to neutralize the acid and therefore enhance the dissolution of PPI and prevent degradation of PPI due to the acid in the stomach. As such, the claimed ratio/amounts do not appear to show any unexpected effect. The examples in the specification (e.g. Fig 3) also appear to show that higher amounts of magnesium hydroxide or magnesium oxide provided higher percentage of dissolution and the prior art also suggests that a higher amount of the antacid would have greater capacity to neutralize the acid and therefore enhance the dissolution of PPI and prevent degradation of PPI due to the acid in the stomach. Thus, the examples and results in the specification do not appear to show that the weight amount/ratio of magnesium hydroxide or magnesium oxide is in fact an unexpected effect.
Applicant argued that Schaefer discloses sodium bicarbonate as the most effective buffer and it would not be easy to predict from Schaefer the effects achieved by excluding sodium bicarbonate as the antacid and including magnesium hydroxide or magnesium oxide. Applicant also argued that Jagadesh presents results comparing the acid neutralizing capacity of aluminum hydroxide and magnesium hydroxide wherein higher amount of magnesium hydroxide results in higher acid neutralization. This does not demonstrate superior acid neutralization of magnesium hydroxide alone as an antacid.
In response, regarding Schaefer, the examiner argues that while Schaefer teaches sodium bicarbonate having the highest increase in pH of Rumen fluid, Schaefer explicitly discloses magnesium oxides neutralized at least twice as many acids as did calcium carbonate or sodium bicarbonate (see e.g. results and discussion). As discussed supra, Hall teaches antacids for neutralizing gastric acid and EP0813424 also teaches antacids agents work through neutralization of gastric acid. The prior art teaches utilizing antacids for neutralizing gastric acid rather than having the largest increase in pH and Schaefer teaches magnesium oxides neutralized at least twice as many acids as did calcium carbonate or sodium bicarbonate. Regarding Jagadesh, while Jagadesh does not expressly teach magnesium hydroxide having superior acid neutralization, the applicant’s attention is respectfully drawn to Gurol and Darwin wherein Gurol et al. (US6066342A; May 23, 2000) discloses that magnesium hydroxide is a stronger acid neutralizing agent as compared to calcium carbonate (see e.g. col. 2, line 1-11; col. 12, line 16-30; entire document). Darwin (Journal of Advanced Veterinary and Animal Research., 6(1): 100-107, March 2019) discloses using magnesium hydroxide and sodium bicarbonate to prevent lactic acid build up in the rumen culture. Sodium bicarbonate is widely known and used for neutralizing acid accumulation in the rumen. Results showed magnesium hydroxide could prevent lactic acid accumulation while sodium bicarbonate did not prevent acidosis and had lactic acid accumulation. (see e.g., Results; Conclusion; Discussion; Entire Document). Thus, it was known in the art that magnesium hydroxide had stronger acid neutralizing ability as compared to sodium bicarbonate or calcium bicarbonate and as such applicant’s argument of unexpected effect is not found persuasive at this time.
Regarding the double patenting rejections, applicant argued neither the ‘317 application nor the ‘178 application discloses a composition having the same PPI to antacid weight ratio as the present claims, nor do they exclude sodium bicarbonate and calcium carbonate.
In response, firstly the examiner argues that both ‘317 and ‘178 teach inclusion of magnesium oxide or magnesium hydroxide and both ‘317 and ‘178 do not teach including either calcium carbonate or sodium bicarbonate. Regarding the claimed ratio, as discussed supra, ‘317 and ‘178 are silent on the amounts/ratio of PPI and magnesium oxide or magnesium hydroxide, and the Hall reference is utilized to cure this deficiency. As discussed supra, the Hall reference expressly teaches the amount/ratio of the PPI and magnesium oxide/magnesium hydroxide which reads on/anticipates the claimed ratio/amounts. The examiner also respectfully directs applicant to the responses above which explain why the claimed ratio does not appear to have any criticality or unexpected results as argued by the applicant.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ALI S SAEED/ Examiner, Art Unit 1616
/SUE X LIU/ Supervisory Patent Examiner, Art Unit 1616
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