DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ claimed invention, filed 9 August 2024, in the matter of Application N° 18/798,864. Said documents have been entered on the record. The Examiner further acknowledges the following:
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
No changes have been made to the originally filed claims. The issue of new matter is moot.
Thus, claims 1-26 represent all claims currently under consideration.
Information Disclosure Statement
Fourteen Information Disclosure Statements (IDS) filed 18 August 2024, 25 August 2024, 15 September 2024, 22 September 2024, 13 October 2024, 27 October 2024, 20 November 2024, 31 December 2024, 19 March 2025, 29 April 2025, 17 May 2025, 18 June 2025, 30 July 2025, and 30 September 2025 are acknowledged and have been considered.
Claim Rejections - 35 USC §102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3, 6-10, and 12 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Liao et al. (WO 2006/084164 A1; IDS reference).
The limitations of the instantly claimed invention are directed to a pharmaceutical composition comprising:
a therapeutically active agent having a molecular weight ranging from 0.5-100 kDa;
SNAC (sodium 8-N-(2-hydroxybenzoyl)aminocaprylate; and
at least one antacid compound.
Liao discloses gastric retention delivery systems and controlled release composition containing a pharmaceutically acceptable active agent and a delivery agent (Abstract; claims). Of particular note are the teachings of Example 8 (shown here):
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Two tablet (i.e., oral) formulations are disclosed which comprise sodium bicarbonate (i.e., antacid), SNAC, and heparin (i.e., a blood clotting factor). SNAC is present in a minimal amount of 230 mg per tablet.
The disclosure of heparin is considered to meet the limitations therapeutically active polypeptide as recited by claim 1, as it is a protein which typically has a molecular weight of about 1.1 kDa (see e.g., PubChem CID 772).
The foregoing is considered to expressly disclose the limitations recited by instant claims 1, 3, 6, and 7.
Instant claims 8 and 9 both recite treating a condition treatable by oral administration of a therapeutically active agent in a subject in need thereof. Claim 1 recites administering the composition of claim 1 while claim 9 recites oral co-administration of an antacid composition comprising at least one antacid and a composition comprising a therapeutically active agent and SNAC (i.e., the composition of claim 1). The Examiner advances that such is disclosed in view of the express teachings of Example 8, since it teaches an oral tablet formulation (see also claim 41). Regarding instant claim 9, the broadest reasonable interpretation of the claim is that the administered composition does not require a gastric acid secretion inhibitor.
The foregoing is also considered to teach the limitations recited by instant claims 10 and 12.
Claim Rejections - 35 USC §103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the Examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicants are advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the Examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-26 are rejected under 35 U.S.C. 103 as being unpatentable over Liao et al. (WO 2006/084164 A2; IDS reference) in view of Shimoni et al. (US Pre-Grant Publication Nº 2010/0303901 A1).
The limitations of the instantly claimed invention are directed to a pharmaceutical composition comprising:
a therapeutically active agent having a molecular weight ranging from 0.5-100 kDa;
SNAC (sodium 8-N-(2-hydroxybenzoyl)aminocaprylate; and
at least one antacid compound.
Liao discloses gastric retention delivery systems and controlled release composition containing a pharmaceutically acceptable active agent and a delivery agent (Abstract; claims). Of particular note are the teachings of Example 8 (shown here):
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Two tablet (i.e., oral) formulations are disclosed which comprise sodium bicarbonate (i.e., antacid), SNAC, and heparin (i.e., a blood clotting factor). SNAC is present in a minimal amount of 230 mg per tablet.
The disclosure of heparin is considered to meet the limitations therapeutically active polypeptide as recited by claim 1, as it is a protein which typically has a molecular weight of about 1.1 kDa (see e.g., PubChem CID 772).
The foregoing is considered to expressly disclose the limitations recited by instant claims 1, 3, 6, and 7.
Instant claims 8 and 9 both recite treating a condition treatable by oral administration of a therapeutically active agent in a subject in need thereof. Claim 1 recites administering the composition of claim 1 while claim 9 recites oral co-administration of an antacid composition comprising at least one antacid and a composition comprising a therapeutically active agent and SNAC (i.e., the composition of claim 1). The Examiner advances that such is disclosed in view of the express teachings of Example 8, since it teaches an oral tablet formulation (see also claim 41). Regarding instant claim 9, the broadest reasonable interpretation of the claim is that the administered composition does not require a gastric acid secretion inhibitor.
The foregoing is also considered to teach the limitations recited by instant claims 10 and 12.
The compositional limitations recited in claim 13 are the same as claim 1 with one notable exception in that the former also recites a core/coat structural limitation. The core is recited as comprising the therapeutically active agent and SNAC and the external coating layer comprises a protective agent selected from either the antacid composition or a protease inhibitor.
Example 8 at ¶[236] teaches the compositional merits as discussed above. Paragraph [237] teaches the structural configuration. Therein, the SNAC, heparin, etc. are formulated to produce an intragranular core to which other components such as sodium bicarbonate are applied extragranularly. This teaching is considered to disclose a SNAC heparin core with no SNAC in the outer coating and also places sodium bicarbonate in the external coating composition. The limitations recited in claims 19-24 are discussed above.
Claim 25 recites that the core, external layer, or both further comprise a pharmaceutically acceptable carrier. Both chitosan and Eudragit RSPO are also formulated into the core with SNAC and heparin, whereas Methocel, citric acid, and magnesium stearate are co-formulated with sodium bicarbonate into the external coating layer.
Lastly, the limitations recited in claim 26 are the same as those recited in claims 8 and 9 with the exception that the composition of claim 13 is now being orally administered. As previously discussed, ¶¶[236]-[237] disclose the compositional and structural merits of Example 8 and disclose further that the final form is a tablet which per the disclosed table, is in the form of a tablet.
Where Liao does not expressly teach the instantly claimed invention is with respect to claims 2, 4, 15, and 16. Claim 2 recites that the composition of claim 1 will further comprise a protease inhibitor.
Liao expressly discloses that the gastric retention composition will contain a pharmaceutically acceptable active agent (see e.g., Abstract; claim 1). Example 8, discussed at length above, is one such showing which uses the protein heparin as the active agent. However, ¶¶[105]-[108] of the reference provide added definition to this component. MPEP §2123(II) states that “[d]isclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments.” In the instant case, the reference conveys to the ordinarily skilled artisan that “biologically or chemically active agents suitable for use in the present invention include, but are not limited to, proteins; polypeptides; peptides; hormones; polysaccharides, and particularly mixtures of muco-polysaccharides; carbohydrates; lipids; small polar organic molecules; other organic compounds; and particularly compounds which by themselves do not pass (or which pass only a fraction of the administered dose) through the gastro-intestinal mucosa and/or are susceptible to chemical cleavage by acids and enzymes in the gastro-intestinal tract; or any combination thereof.” Paragraph [108] more specifically defines such agents as including such compounds as the preferably disclosed heparin, insulin, as well as other such compounds as protease inhibitors. The Examiner concedes that the reference teaches a sizeable list of agents from which may be selected protease inhibitors and thus it would appear that there exists no motivation for the skilled artisan to specifically select protease inhibitors to combine with the preferred compositions.
However, this deficiency is still considered to be remedied by Shimoni.
Shimoni discloses enteric coated capsules and tablets for oral delivery of a protein, polypeptide, or peptide drug, in particular, for oral delivery of insulin, comprising microparticles of the protein, polypeptide, or peptide drug, microparticles of a protease inhibitor and, optionally, microparticles of an absorption enhancer (see e.g., Abstract; claim 1). It is noted further that the protein, polypeptide, or peptide drug microparticles and protease inhibitor microparticles are both embedded within the enteric polymer matrix which is again disclosed as forming the outer coating layer of the dosage form. Claim 2 of the reference teaches that the two populations of microparticles may be found in the same layer of enteric polymer matrix whereas claims 3 and 6 teach and suggest that the two populations of microparticles will be located in different enteric polymer matrices. Claim 18 discloses the protease inhibitor as being “SBTi” or soybean trypsin inhibitor.
Liao also discloses the formation of tablets. Liao discloses, for instance, in Example 8, formulating tablets having a granulated core composed of SNAC and heparin with an added granulated layer on top of the core comprising granulated antacid sodium bicarbonate. The tablets are further taught as being formed through the compression of the granules. Paragraph [246] teaches different SNAC formulations, one of which (Formulation #2) is SNAC particles coated with Eudragit RS30D. However, Liao does not appear to teach preparing tablets comprising an outer enteric coating layer.
Shimoni again is considered to remedy this deficiency. Though Liao does teach and suggest combining protein, polypeptide, or peptide drugs with a protease inhibitor for delivery from the practiced tablet, the reference does fail to teach them being structurally separated within the same dosage form. Shimoni on the other hand, compositionally and structurally provides such a teaching. Motivation to combine the teachings and produce such a dosage form is considered to be provided in the name of the claimed components themselves. Notably, both references disclose administering a tablet form which delivers protein, polypeptide, or peptide drugs. Thus, the obvious goal in each case is to maximize delivery of the protein, polypeptide, or peptide drugs and minimize their breakdown. A protease inhibitor inherently accomplishes this very goal. Liao teaches and suggests releasing these two components simultaneously, whereas Shimoni controls it releasing protease inhibitor ahead of the protein, polypeptide, or peptide drugs so as to inhibit that which will breakdown the drug. The inhibitor microparticles are embedded in a polymer matrix which is “enteric” in nature which means it will only break down when in the presence of particular pH values in the GI tract.
Thus, a person in possession of the combined teachings of Liao and Shimoni would have been immediately motivated to produce the instantly claimed pharmaceutical dosage forms. A reasonable expectation of successfully accomplishing the claimed compositions and methods of treating is derived from the specific core/“coating” teachings exemplified by Liao in Example 8 as well as the added teachings provided by Shimoni. Shimoni motivates the skilled artisan to add an enteric coating and embed therein a protease inhibitor. In so doing, a person of skill in the art produces a composition which would be expected to maximize the release and survival of a protein, polypeptide, or peptide drug on its release from the delivery system.
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 filed, absent a clear showing of evidence to the contrary.
Lastly, the limitations of claim 4 recite that at least 90 wt% of the composition of claim 1 consist of the ingredients recited therein, namely the therapeutically active agent, SNAC, and at least one antacid compound.
Liao does not appear to expressly teach such a percentage. Example 8, for instance discloses that these three compounds represent about 69% of the overall tablet composition: SNAC (230 mg/495.5mg tablet), heparin (85.25 mg/495.5mg tablet), and sodium bicarbonate (24.78 mg/495.5mg tablet). Methocel is disclosed by Liao as possessing several functions one of which is for controlled release of the core composition. See, for example, ¶¶[124]-[128], the first paragraph of which teaches that the composition will contain anywhere from 1-60% by weight of the release controlling polymer. Example 8 uses 20% by weight or 99.1 mg of Methocel. At the low end of the spectrum, reducing the composition to 1% or about 4.9 mg would increase the percent presence of the remaining components of interest. Thus, in so manipulating the remaining excipient percentages of the tablet formulation, a person of skill in the art would have a reasonable expectation of being able to adjust the amount of active, SNAC and antacid present in the final tablet formulation. MPEP §2144.05(II)(B.) states that “a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation, because “obvious to try” is not a valid rationale for an obviousness finding.” In the instant case, a person of skill in the art would reasonably expect that increasing the amount of protein, peptide, or polypeptide drug present in the tablet to increase the likelihood of the survival and uptake of said drug in the absence of a protease inhibitor.
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 filed, absent a clear showing of evidence to the contrary.
Nonstatutory 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 1-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of Burshtein et al. (USPN 10,583,177 B2). Although the claims at issue are not identical, they are not patentably distinct from each other.
The limitations of claims 1 and 4 of the ‘177 patent read on the limitations of instant claims 1 and 3.
The limitations of claim 2 of the ‘177 patent read on the limitations of instant claim 2.
The limitations of claim 3 of the ‘177 patent read on the limitations of instant claim 4.
The limitations of claim 5 of the ‘177 patent read on the limitations of instant claim 5.
The limitations of claim 6 of the ‘177 patent read on the limitations of instant claim 6.
The limitations of claim 7 of the ‘177 patent read on the limitations of instant claim 7.
The limitations of claim 8 of the ‘177 patent read on the limitations of instant claim 8.
The limitations of claim 9 and 11 of the ‘177 patent read on the limitations of instant claim 9.
The limitations of claim 10 of the ‘177 patent read on the limitations of instant claim 10.
The limitations of claims 12 and 14 of the ‘177 patent read on the limitations of instant claims 13, 18, and 22.
The limitations of claim 13 of the ‘177 patent read on the limitations of instant claim 14.
The limitations of claim 14 of the ‘177 patent read on the limitations of instant claim 15.
The limitations of claim 15 of the ‘177 patent read on the limitations of instant claim 16.
The limitations of claim 16 of the ‘177 patent read on the limitations of instant claim 17.
The limitations of claim 17 of the ‘177 patent read on the limitations of instant claim 19.
The limitations of claim 18 of the ‘177 patent read on the limitations of instant claim 20.
The limitations of claim 19 of the ‘177 patent read on the limitations of instant claim 21.
The limitations of claim 20 of the ‘177 patent read on the limitations of instant claim 23.
The limitations of claim 21 of the ‘177 patent read on the limitations of instant claim 24.
The limitations of claim 22 of the ‘177 patent read on the limitations of instant claim 25.
The limitations of claim 23 of the ‘177 patent read on the limitations of instant claim 26.
Based on the overlapping teachings of the ‘177 patent with the instantly claimed limitations, were the ‘177 patent available as prior art, the limitations disclosed by the claims alone would render the instantly claimed inventions prima facie obvious where they did not anticipate them.
Claims 1-3, 5, 6, 8-15, 17-20, 23, 24, and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of Burshtein et al. (USPN 12,076,373 B2). Although the claims at issue are not identical, they are not patentably distinct from each other.
The limitations of claims 1, 4, 7, and 8 of the ‘373 patent read on the limitations of instant claims 1, 3, 6, and 19.
The limitations of claims 2 and 3 of the ‘373 patent read on the limitations of instant claim 2.
The limitations of claims 5 and 6 of the ‘373 patent read on the limitations of instant claim 2.
The limitations of claim 9 of the ‘373 patent read on the limitations of instant claim 20.
The limitations of claim 10 of the ‘373 patent read on the limitations of instant claim 8.
The limitations of claim 11 of the ‘373 patent read on the limitations of instant claims 9-12.
The limitations of claims 12, 13, and 17 of the ‘373 patent read on the limitations of instant claims 13-15, 17, and 18.
The limitations of claims 14 and 16 of the ‘373 patent read on the limitations of instant claims 23 and 24.
The limitations of claim 15 of the ‘373 patent read on the limitations of instant claim 18.
The limitations of claim 18 of the ‘373 patent read on the limitations of instant claim 26.
Based on the overlapping teachings of the ‘373 patent with the instantly claimed limitations, were the ‘373 patent available as prior art, the limitations disclosed by the claims alone would render the instantly claimed inventions prima facie obvious where they did not anticipate them.
All claims have been rejected; no claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Jeffrey T. Palenik whose telephone number is (571) 270-1966. The Examiner can normally be reached on 9:30 am - 7:00 pm; M-F (EST).
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Jeffrey T. Palenik/
Primary Examiner, Art Unit 1615
Prosecution Insights