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 .
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 10 and 12 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 10 recites the limitation "said carbonate salt of an alkali metal” in claim 3. There is insufficient antecedent basis for this limitation in the claim. For the sake of compact prosecution, it is assumed that claim 10 depends on claim 4 for the purposes of prior art consideration only, but applicant must amend the dependency of claim 10 to overcome the present rejection.
Claim 12 depends on claim 4 and states, “wherein the carbonate salt of an alkali metal, when present, replaces 1/5 to 1/3 by weight of the basic amount of magnesium carbonate”. The expression “when present” renders the claim confusing as the base claim, claim 4, requires that the composition contains a carbonate salt of an alkali metal. It is not clear whether the scope of claim 12 also includes a composition which does not contain such carbonate salt.
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.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Eutick (US 20140141087 A1, published on May 22, 2014) as evidenced by Tai (US 5013557 A) and as evidenced by Tai (US 5013557 A, published May 7, 1991) and in view of Buehler et al. (US 4869902 A, September 26, 1989) (“Buehler” hereunder).
Claim 1 is directed to a combination consisting of magnesium alginate having a ratio of mannuronic acid residues with respect to guluronic acid residues (M/G) greater than 1.0; sucralfate amorphous powder; and basic magnesium carbonate.
Eutick teaches sucralfate and alginates are non-absorbable neutralizing salts which act as coating agents preventing the stomach acid from reaching an inflamed area by forming a physical barrier over the region. See [0006, 0039]. The reference teaches magnesium carbonate is an absorbable anti-acidic salt commonly added to acid neutralizing salts or coatings. See [0038].
It is well settled in patent law that combining art-recognized functional equivalents for same purpose is prima facie obvious. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980); MPEP 2144. 06, I. In this case, Eutick establishes that sulcralfate, alginate salts and magnesium carbonate are old and well-known antiacid agents used in oral antacid composition for treating gastritis associated with hyperacidity, dyspepsia, gastroesophageal reflux disease, etc. See [0002]. Combining these conventional antiacid agents to make a combination useful for the same purpose is prima facie obvious.
Sucralfate is in the form of a white amorphous powder. See Tai, col. 6, lines 8 – 14. Magnesium carbonate is inherently basic as the carbonate ion hydrolyzes in water to form bicarbonate and hydroxide, which raises the pH.
Although Eutick does not specifically disclose magnesium alginate, Buehler teaches the magnesium salt of alginic acid having a ratio of mannuronic to guluronic acid of about 0.4:1 to about 2:1 is useful in forming a gelatinous foamy mass and barrier to gastric reflux when reacted with gastric acid in the stomach. See Buehler, col. 2, lines 54 – 68. Given the teachings of Eutick to use an alginate salt as an antiacid coating agent, one of ordinary skill in the art before the effective filing date of the present application would have been obviously motivated to look to prior art such as Buehler and used magnesium alginate described therein.
Claims 3-7, 11-19 are rejected under 35 U.S.C. 103 as being unpatentable over McCullough (US 5447918, cited in IDS) as evidenced by Tai and in view of Buehler.
Claim 3 depends on claim 1 and is directed to an aqueous oral pharmaceutical composition comprising the combination according to claim 1, together with one or more pharmaceutically acceptable carriers and/or excipients. The scope of the aqueous oral pharmaceutical composition is open to include any other components not recited in the claim.
.McCullough teaches a gastrointestinal anti-irritant composition comprising sulcralfate and at least one anti-acid epigastralgic relieving agents in a weight to weight ratio of between 0.5:1 to 1:3; the at least one anti-acid agent can be metal salt of alginate.
Example 5 disclose such formulation comprising sucralfate (250-500 mg/ 5ml) and magnesium alginate (500-600 mg/ 5 ml) and aluminum hydroxide-magnesium carbonate gel (150-300 mg/ 5 ml) in an aqueous vehicle. The compositions are said to be useful in non-ulcer, non-infectious disorders such as reflux esophagitis, heart burn, acid indigestion, etc. The reference teaches that magnesium alginate is used as an “epigastralgia-relieving agent” whose main role is surface-active, GI-mucus protective (anti-irritant) activity, especially when combined with sucralfate. See col. 7, lines 39 – 53.
Sucralfate is in the form of a white amorphous powder. See Tai, col. 6, lines 8 – 14. Magnesium carbonate is inherently basic as the carbonate ion hydrolyzes in water to form bicarbonate and hydroxide, which raises the pH.
McCullough fails to specifically disclose the ratio of mannuronic acid residues with respect to guluronic acid residues (M/G) as defined in claim 1.
Buehler teaches an antacid composition comprising magnesium alginate and an antiacid material useful in the treatment of reflux esophagitis. See abstract. The reference teaches that a gas-producing material such as bicarbonate and alginate form a well-knitted raft; the rigidity, strength and thickness of the foamy mass depends on the ratio of the gas-producing material to the alginate and the thickness of the alginate, and the presence of any divalent cations which function as a cross-linking agent. The reference teaches that the preferred alginic acid used to prepare the magnesium salt comprises a polymer chain of mannuronic acid and guluronic acid segments in a ratio of mannuronic to guluronic acid of about 0.:1 to about 2:1, and more preferably about 0.4: 1 to about 1:1, which overlaps with the present ratio of greater than 1.0.
Magnesium alginate having MG ratio of 1:1 – 2:1. See col. 2, lines 54 – 68. Buehler discloses a liquid suspension comprising magnesium alginate and magnesium carbonate in sorbitol. See Example 1.
As both McCullough and Buehler teach magnesium alginate useful as a protective barrier to treat gastrointestinal disorders and irritations, the magnesium alginate used in both formulations would obviously have the same M/G ratio.
As for claim 3, Example 5 of McCullough teaches pharmaceutically acceptable excipients including water. Since the scope of claim 3 is open to include components not recited in the claim, the disclosed formulation would render Claim 3 obvious although disclosed formulation contains aluminum hydroxide and potassium bicarbonate.
Regarding claim 4, McCullough teaches that calcium carbonate, magnesium carbonate and aluminum hydroxide are all epigastralgia-relieving antiacid agents and form antiacid anti-irritant compositions when combined with sucralfate. See col. 7, lines 39 – 53. Thus, incorporating to calcium carbonate in to the composition of Example 5 to enhance the anti-irritant effects of the composition would have been prima facie obvious. Alternatively, combining art-recognized functional equivalents known for the same purposes is also prima facie obvious. See MPEP 2144.06, I. Since McCullough establishes that calcium carbonate and magnesium carbonate are known epigastralgia-relieving antiacid agents that can be used with sucalfate, combining the two carbonate salts for the same purpose of making a similar antiacid formulation would have been prima facie obvious.
Regarding claims 5-6, Buehler teaches the M/G ratio of the magnesium alginate is up to 2:1. See col. 2, lines 54 – 68.
Regarding claim 7, it is well known in patent law that a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). In this case, since “about 2.5” is close to 2, thus the properties of the McCullough formulation are expected to have similar properties of the presently claimed composition when the M/G ratio is 2.
Regarding claim 11, Example 5 disclose such formulation comprising magnesium alginate (500-600 mg/ 5 ml), sucralfate (250-500 mg/ 5ml) and aluminum hydroxide-magnesium carbonate gel (150-300 mg/ 5 ml) in an aqueous vehicle. The proportions of the ingredients in w/v are: 10-12 % w/v magnesium alginate, 5-10 % w/v sucralfate amorphous powder, and 3 -6 % w/v aluminum hydroxide-basic magnesium carbonate. Although the 3-6% of the magnesium carbonate gel include the amount of aluminum hydroxide, since aluminum hydroxide and magnesium carbonate are both disclosed as antiacid epigastralgic relieving agents, the examiner assumes that these functionally equivalent agents are used in an equal amount unless shown otherwise; as the proportion of magnesium carbonate in the McCllough formulation is estimated to be about 1.5-3 w/v of the composition, it is viewed that the prior art is not distinct from the presently claimed composition.
Claim 12 recites “wherein the carbonate salt of an alkali metal, when present, replaces 1/5 to 1/3 by weight of the basic amount of magnesium carbonate in the composition. It is well settled in patent law that combining or substituting art-recognized functional equivalents known for the same purposes is prima facie obvious. See MPEP 2144.06. As discussed above, since McCullough establishes that calcium carbonate and magnesium carbonate are known epigastralgia-relieving antiacid agents that can be used with sucralfate, combining or substituting the two carbonate salts for the same purpose of making a similar antiacid formulation would have been prima facie obvious. As the reference generally teaches the proportion of the epigastralgia-relieving antiacid agents that can be used with respect to the amount of sucralfate, one of ordinary skill in the art would have been obviously motivated to optimize the total amount of the antiacids. Since using multiple antiacids would reduce the amount of the individual antiacids, finding the amounts of each components by routine experimentations would have been well within the skill in the art.
Regarding claims 13 and 14, McCullough example 5 contains pharmaceutically acceptable excipients including sorbitol.
Regarding claims 15 and 17, the disclosed liquid formulation in McCullough is in multi-dose form and contains no calcium salts.
Regarding claim 16, Example 5 disclose such formulation comprising magnesium alginate (500-600 mg/ 5 ml), sucralfate (250-500 mg/ 5ml) and aluminum hydroxide-magnesium carbonate gel (150-300 mg/ 5 ml) in an aqueous vehicle. Although the concentration of 150-300 mg/5 ml the magnesium carbonate gel include the amount of aluminum hydroxide, since aluminum hydroxide and magnesium carbonate are both disclosed as antiacid epigastralgic relieving agents, the examiner assumes that these functionally equivalent agents are used in an equal amount unless shown otherwise; as the concentration of magnesium carbonate in the McCllough formulation is estimated to be about 75-150 mg/5ml, it is viewed that the prior art is not distinct from the presently claimed composition.
Regarding claims 18, Examples 4 and 9 were conducted with human volunteers; Example 5 is obviously suitable and intended for human use. McCullough also discusses a study in which a mucosal protective effect was observed in animals that were treated with sucralfate gel, which indicates that the McCullough formulation would be also suitable for veterinary therapy. See col. 5, lines 53 – col. 6, line 11.
Regarding claim 19, McCullough teaches using the antiacid formula in treating gastrointestinal mucosal irritations associated with esophagitis, gastritis, etc. See col. 1, line 15 – col. 2, line 33.
Claims 8 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over McCullough, Tai and Buehler as applied to claims 3-7, 11-19 as above, and further in view of Zagnoli et al. (US 5321013, June 14, 1994) (“Zagnoli” hereunder).
Mccllough fails to teach the particle size of sucralfate.
Zagnoli teaches pharmaceutical compositions in the form of stable sucralfate suspensions free of suspending agents, wherein an average particle size (mean volume-surface diameter) is 6 microns and distribution is 2-30 microns. See col. 6, lines 10-15. The reference teaches that the compositions are effective in treating pyorosis and epigastralgia and improving reflux esophagitis and gastroduodenal erosion. See col. 2, lines 1-9. The reference teaches that the sucralfate wet gel with such particle size range acts as its own thickening and suspending agent and there is no need to separately micronize sucralfate powder.
Given the teachings of using sucralfate in making pharmaceutical compositions for treating gastrointestinal irritation, one of ordinary skill in the art would have been obviously motivated to look to prior art such as Zagnoli for the type of sucralfate useful in making the McCullough formulation. Since the latter teaches that sucralfate powder having an average particle size of 6 microns with a narrow distribution range of 2-30 microns can be used in making a pharmaceutical liquid suspension without suspending or thickening agents and without micronization, the skilled artisan would have been obviously motivated to combine the teachings of the references in a reasonable expectation of successfully producing the McCullough formulation with more convenience and less additives.
Claims 10 are rejected under 35 U.S.C. 103 as being unpatentable over McCullough, Tai and Buehler as applied to claims 3-7, 13-19 as above, and further in view of Kim et al. (WO 2013187720 A1, published December 19, 2013) (“Kim” hereunder).
McCullough fails to teach sodium carbonate.
Kim teaches a composition for treating gastroesophageal reflux, the composition comprising a metal salt of alginate and alkali metal bicarbonate or carbonate salts. See p. 4, [42]. The reference teaches that alkali metal bicarbonate or alkali metal carbonate is used to produce gas by which the alginic acid-generated gel may float. The reference teaches sodium bicarbonate, potassium bicarbonate, sodium carbonate and potassium carbonate can be used. See p. 5, [52]. Example 7 employs sodium bicarbonate, and the reference teaches that replacing sodium bicarbonate with other alkali metal bicarbonate or alkali metal carbonate salts would give similar results.
It is well settled in patent law that substituting art-recognized functional equivalents is prima facie obvious. See MPEP 2144.06 II. In this case, Kim establishes that potassium bicarbonate in Example 5 of the reference and sodium carbonate are well known alkali metal bicarbonate and carbonate for use with magnesium alginate to form a protective barrier for the upper GI track and treat gastrointestinal irritation. It follows that substituting one for the other for the same purposes would have been prima facie obvious.
Allowable Subject Matter
Claim 2 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 1 and 3-19 are rejected
Claim 2 is objected to.
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/GINA C JUSTICE/Primary Examiner, Art Unit 1617