DETAILED ACTION
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 the Claims
Claims 1-3, 5-7, 9-22, 24, 29-35, 37, 38 are pending. Claims 4, 8, 23, 25-28, 36, 39 are cancelled.
Status of Priority
The present application is a 35 U.S.C. § 371 national stage patent application of International patent application PCT/IB2021/050477, filed on January 22, 2021. This application also claims the benefits of foreign priority to AU2020900183, filed on January 23, 2020.
Election/Restriction
Examiner previously required a restriction of the claimed inventions. The requirement filed on April 30, 2025 is now withdrawn and the prosecution will continue with a first non-final office action on the merits.
Examiner’s Note
According to MPEP § 2114, section II:
“‘[A]pparatus claims cover what a device is, not what a device does.’ Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a ‘recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus’ if the prior art apparatus teaches all the structural limitations of the claim.”
This can also be translated to a compound claim. A compound claim covers what a compound is, not what a compound does. Therefore, a claim containing a recitation with respect to the manner in which a claimed compound is intended to be employed does not differentiate the claimed compound from a prior art compound if the prior art compound teaches all the structural limitations of the claim. Therefore, claims 1-3, 5-7, 9-22, and 24 of the instant application are all compound claims (and are substantial duplicates of each other – See “Claim Objections” section below) that are directed towards a bile acid or a pharmaceutically acceptable salt thereof, wherein the bile acid is chenodeoxycholic acid or deoxycholic acid.
Information Disclosure Statement
The information disclosure statement filed on November 02, 2022 cites a non-patent literature written by Yin et al. There is no non-patent literature written by Yin et al. provided in the application file wrapper. Therefore, the Examiner did not consider this reference. All other references have been considered.
Specification - Abstract
The abstract of the disclosure is objected to because the sheet presenting the abstract includes other parts of the application or other material. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Specification - Disclosure
The disclosure is objected to because of the following informalities:
On pg. 33, lines 15-21, a key is provided as follows:
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On line 20, the square symbol should be the “±” symbol instead.
On pg. 36, line 14-16, it states:
“It can be seen from the table below that at the concentrations employed, neither chenodeoxycholate nor EDTA were able to enhance uptake of the protein on their own.”
However, the table does not include data for the condition where EDTA is added to the cell culture independently (i.e., without presence of chenodeoxycholate):
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Appropriate correction is required.
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claim 31 is objected to for the following informalities:
Claim 31 should be rewritten as follows:
“A pharmaceutical composition comprising:
a) a bile acid or a pharmaceutically acceptable salt thereof, wherein said bile acid is chenodeoxycholic acid or deoxycholic acid; and
b) a therapeutic compound;
wherein the bile acid or salt and therapeutic compound are encapsulated by a coating which (a) restricts dissolution of the bile acid or salt and therapeutic compound under aqueous conditions at a pH of 7.4 but ceases to restrict dissolution of the bile acid or salt and therapeutic compound at a pH which is lower than 7.4, and/or (b) contains one or more moieties capable of binding to a target cell population within the body.”
Claims 2, 3, 6, 7, 9-22, and 24 are objected to as being a substantial duplicate of claim 1 as the only difference is a statement of intended use, which does not limit the scope of the claim under the broadest reasonable interpretation and therefore is not given material weight. Note In re Tuominen 671 F.2d 1359, 1360, 213 USPQ 89, 90 (C.C.P.A. 1982).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 29, 30, 33, 34, 35, 37, and 38 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In evaluating the enablement question, several factors are to be considered. According to In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), these factors include:
1) The nature of the invention,
2) the state of the prior art,
3) the predictability or lack thereof in the art,
4) the amount of direction or guidance present,
5) the presence or absence of working examples,
6) the breadth of the claims, and
7) the quantity of experimentation needed, and
8) the level of the skill in the art.
In the instant case, the Wands factors are relevant for the following reasons:
The nature of the invention
The nature of the invention claims:
a bile acid or a pharmaceutically acceptable salt thereof, wherein said bile acid is chenodeoxycholic acid or deoxycholic acid,
a pharmaceutical composition comprising:
a bile acid or a pharmaceutically acceptable salt thereof, wherein said bile acid is chenodeoxycholic acid or deoxycholic acid;
a therapeutic compound; and
one or more further compounds selected from fusogenic lipids, cell penetrating peptides, lysosomotropic agents, membrane-disruptive peptides, membrane-disruptive polymers, photochemical internalisation agents, and agents that alter intracellular vesicle transport, and
a pharmaceutical composition comprising:
a bile acid or a pharmaceutically acceptable salt thereof, wherein said bile acid is chenodeoxycholic acid or deoxycholic acid; and
a therapeutic compound;
wherein the bile acid or salt and therapeutic compound are encapsulated by a coating which (a) restricts dissolution of the bile acid or salt and therapeutic compound under aqueous conditions at a pH of 7.4 but ceases to restrict dissolution of the bile acid or salt and therapeutic compound at a pH which is lower than 7.4, and/or (b) contains one or more moieties capable of binding to a target cell population within the body.
State of the prior art
Prior art referenced:
Modi et al. (Modi) (US5653987A; published August 5, 1997)
Prior art (Modi) discloses a composition comprising insulin (1 mL of Novolin-R [trademark] fast acting insulin; col. 6, lines 63-64), 0.1g monoolein, 0.25g deoxycholate, 0.25g polyoxyethylene 9-lauryl ether, and a small quantity of distilled water (col. 7, lines 39-42).
It is noted here that monoolein is a type of fusogenic lipid (Angelov, B. et al. DNA/Fusogenic Lipid Nanocarrier Assembly: Millisecond Structural Dynamics. J. Phys. Chem. Lett. 2013, 4, 1959-1964.;abstract, 2nd sentence). Therefore, the composition disclosed by Modi reads on instant claim 29.
In summary, the prior art discloses the quantity of each main component in a pharmaceutical composition.
The presence or absence of working examples, amount of direction or guidance present, and quantity of experimentation necessary
In the instant case, the specification is not enabling because examples 1-15 provide no working examples of a pharmaceutical composition comprising:
a bile acid or salt thereof,
a therapeutic compound, and
one or more further compounds selected from fusogenic lipids, cell penetrating peptides, lysosomotropic agents, membrane-disruptive peptides, membrane-disruptive polymers, and agents that alter intracellular vesicle transport
that is employed in conjunction with EDTA. The prior art also does not disclose how much EDTA should be employed in conjunction with a pharmaceutical composition comprising a therapeutic compound, a fusogenic lipid, and a bile salt. In the absence of clear guidance, a person of ordinary skill in the art would require undue experimentation to determine the quantity of fusogenic lipid or other agents like cell penetrating peptide, lysosomotropic agent, membrane-disruptive peptide, membrane-disruptive polymer, or an agent that alters intracellular vesicle transport that is suitable for a pharmaceutical composition, wherein the composition is employed in conjunction with EDTA (pertains to instant claims 29 and 30).
Further, there are no working examples of multiple agents added to the pharmaceutical composition of claim 32 that can stabilize and/or enhance the formation of the bile acid micelle structure. The specification only provides a working example of one agent, propyl gallate, as an agent that can stabilize or enhance the formulation of the bile acid micelle structure (Instant specification, examples 2 and 7; pertains to instant claim 33).
The breadth of the claims
The claims are broad insofar as the instant claims recite a therapeutic compound, fusogenic lipid, cell penetrating peptide, lysosomotropic agent, membrane-disruptive peptide, membrane-disruptive polymer, photochemical internalization agent, and an agent that alters intracellular vesicle transport which can encompass many different chemical compounds and/or macromolecules.
Claims 34, 35, 37, and 38, which are dependent on claim 29, are also rejected for further requiring and/or reciting non-enabling elements of claim 29.
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 5, 14, 19, 33, 34, and 38 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.
Regarding claims 5, 14, 19, and 34, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 14, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 33 recites the limitation "said micellar form" in item (a) and (b). There is insufficient antecedent basis for this limitation in the claim. Claim 33 depends on claims 31 and 32. Neither claims 31 nor 32 mention a “micellar form”.
Claim 38 recites the limitation "concentration of the EDTA". There is insufficient antecedent basis for this limitation in the claim. Claim 38 depends on claim 29 which does not mention EDTA.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2, 3, 6, 7, 9-22, and 24 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Since claims 2, 3, 6, 7, 9-22, and 24 are substantial duplicates of claim 1 (See “Claim Objections” section above), these claims are not further limiting the subject matter of the claim upon which it depends (i.e., claim 1). Therefore, claims 2, 3, 6, 7, 9-22, and 24 are written in improper dependent form.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-3, 6-7, 9-22, and 24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because they encompass compounds that are a product of nature and, therefore, is not patentable.
See prior art:
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases;
2012-. Bile Acids. [Updated 2017 Sep 25]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548626/
Specifically, the prior art teaches that the “primary bile acids synthesized in the liver are cholic and chenodeoxycholic acid” and “[i]n the intestine, the primary bile acids are often converted by colonic bacteria to the secondary bile acids, predominantly deoxycholic acid and lithocholic acid” (LiverTox, Introduction section, 1st paragraph, 5th and 6th sentence).
Note on 35 USC § 102 and § 103 Rejections
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.
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, 5-7, 9-22, 24, 29, 31, 34, 35, and 37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by the prior art as explained below.
Regarding instant claims 1-3, 5-7, 9-22, and 24:
Modi et al. (Modi) (US5653987A; published August 5, 1997)
Modi discloses the bile salts: chenodeoxycholate and deoxycholate (col. 4, line 61).
Regarding instant claims 29, 34, 35, and 37:
Modi et al. (Modi) (US5653987A; published August 5, 1997)
The issued patent of Modi claims the following invention:
“A liquid pharmaceutical agent formulation suitable for oral or nasal delivery comprising a proteinic pharmaceutical agent, water and at least two absorption enhancing compounds, wherein said absorption enhancing compounds are… a combination of sodium deoxycholate, chenodeoxycholate, polyoxyethylene 9-lauryl ether and monoolein… wherein the amount of each of the absorption enhancing compounds is present in a concentration of from 1 to 10 wt./wt.% of the total formulation” (Modi, claim 1).
It is noted here that monoolein is a type of fusogenic lipid (Angelov, B. et al. DNA/Fusogenic Lipid Nanocarrier Assembly: Millisecond Structural Dynamics. J. Phys. Chem. Lett. 2013, 4, 1959-1964.;abstract, 2nd sentence). Therefore, claim 1 of Modi encompasses the composition disclosed in instant claims 29, 34, 35, and 37.
Modi also explicitly discloses a composition comprising insulin (1 mL of Novolin-R [trademark] fast acting insulin; col. 6, lines 63-64), 0.1g monoolein, 0.25g deoxycholate, 0.25g polyoxyethylene 9-lauryl ether, and a small quantity of distilled water (col. 7, lines 39-42) (reads on instant claims 29 and 35).
Regarding instant claim 31:
New (US20060122097A1; published June 8, 2006)
New discloses a pharmaceutical composition comprising a mixture of (claim 1):
an active macromolecular principle; and
a non-conjugated bile acid or salt; and
propyl gallate
wherein the composition is coated with an enteric coating which becomes permeable at a pH from 3 to 7 (claim 3).
Note:
Claims 1 and 3 of New corresponds to claims 1 and 12 of issued U.S. Patent No. 8,314,058 B2 published on November 20, 2012 and encompasses instant claim 31.
The active macromolecular principle is a therapeutic compound (pg. 1, para. 0014).
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.
Claims 29-35, 37, and 38 are rejected under 35 U.S.C. 103.
Rejection part 1:
Claims 31-33 are rejected under 35 U.S.C. 103 as being unpatentable over
New (US20060122097A1; published June 8, 2006) and
Modi et al. (Modi) (US5653987A; published August 5, 1997)
New teaches the administration of a formulation as a dry compacted powder to juvenile pigs. The formulation (pg. 5, para. 0059, 1st sentence) comprises 100 iu insulin (a therapeutic compound), 66 mg chenodeoxycholic acid (a permeation enhancer [i.e., an absorption enhancer]; pg. 1, para. 0002), and 33 mg propyl gallate (a compound that enhances chenodeoxycholate solubility in water at pH levels below pH 7; pg. 1, para. 0007, 2nd sentence). The pharmaceutical compositions claimed by New is coated with an enteric coating which becomes permeable at a pH from 3 to 7 (claim 3; Suitable enteric coatings are well known in the art. See New, pg. 4, para. 0042).
New does not teach of a formulation comprising EDTA. Modi is relied upon for this disclosure.
The issued patent of Modi claims the following invention:
“A liquid pharmaceutical agent formulation (i.e., a pharmaceutical composition) suitable for oral or nasal delivery comprising a proteinic pharmaceutical agent, water and at least two absorption enhancing compounds, wherein said absorption enhancing compounds are selected from the group consisting of… a combination of chenodeoxycholate, sodium lauryl sulphate and disodium EDTA… wherein the amount of each of the absorption enhancing compounds is present in a concentration of from 1 to 10 wt./wt.% of the total formulation” (claim 1). “The formulation is particularly adapted to oral delivery of insulin” (abstract, last sentence).
Therefore, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the claimed invention to take the formulation disclosed in New and add EDTA as the second absorption enhancing compound. There is motivation to include two absorption enhancing compounds in a composition because Modi teaches that “orally administered insulin formulation which contains only one absorption enhancer…has very little metabolic effect on the blood glucose levels” (col. 6, lines 50-55). However, when at least two absorption enhancers are in the pharmaceutical composition, “orally administered insulin formulation has a metabolic effect on the blood glucose levels” (col. 6, lines 14-15).
Recall that Modi’s invention encompasses a pharmaceutical composition comprising at least two absorption enhancer compounds: EDTA and chenodeoxycholate (Modi, claim 1). Therefore, a POSITA would further been motivated to combine EDTA with the formulation of New comprising chenodeoxycholic acid with a reasonable expectation of success since chenodeoxycholic acid is very similar in structure with chenodeoxycholate as the former is the free acid form of the latter. Therefore, a pharmaceutical composition comprising insulin, chenodeoxycholic acid, EDTA, and propyl gallate wherein the composition is coated with an enteric coating which becomes permeable at a pH from 3 to 7 is obvious to make and reads on instant claims 31-33.
Note:
In instant claim 33, the one or more additional agent is described to
stabilize the micellar form of the bile acid or salt thereof; and/or
enable or enhance the formation of said micellar form.
According to the instant specification, propyl gallate is an example of an agent that can perform actions (a) and (b) (pg. 19, para. 0066, lines 26-27). New does not describe propyl gallate to perform actions (a) and (b). Instead, New describes propyl gallate as a compound that enhances chenodeoxycholate solubility in water at pH levels below pH 7; pg. 1, para. 0007, 2nd sentence. However, according to MPEP § 2112.01, section I:
“When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent.”
In other words, the property of propyl gallate being able to stabilize or enhance the formation of a bile acid micelle structure is inherent to the compound.
Therefore, a composition which comprises a therapeutic compound (like insulin), a bile acid (like chenodeoxycholic acid), EDTA, and an agent that can stabilize or enhance the formation of the bile acid micelle (like propyl gallate) reads on instant claim 33 and is obvious to make in view of the teachings taught by New and Modi as explained above.
Rejection part 2:
Claims 29, 30, 34, 35, 37, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over
New (US20060122097A1; published June 8, 2006),
Hentz et al. (Hentz) (Hentz, N. G. et al. Synthesis and Characterization of Insulin−Fluorescein Derivatives for Bioanalytical Applications. Anal. Chem. 1997, 69, 4994-5000.), and
Modi et al. (Modi) (US5653987A; published August 5, 1997)
The teachings of New as they apply to claims 31-33 are as discussed in “Rejection – Part 1” and incorporated herein.
New does not teach of a photochemical internalization agent. According to the instant specification, a fluorescent label such as fluorescein isothiocyanate or a compound comprising it is considered a photochemical internalization agent (pg. 24, lines 17-18). Hentz is relied upon for this disclosure.
Hentz discloses the labelling of human insulin with fluorescein isothiocyanate (FITC) (abstract, 1st sentence) for application in bioanalytical studies (pg. 4994, right col., 2nd paragraph, 1st sentence).
Neither New nor Hentz discloses a pharmaceutical composition comprising two absorption enhancers wherein one of the absorption enhancers is EDTA. Modi is relied upon for this disclosure.
The teachings of Modi as they apply to claims 31-33 are as discussed in “Rejection – Part 1” and incorporated herein.
Therefore, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the claimed invention to replace some or all of the insulin in the formulation disclosed by New with FITC-labeled insulin (reads on instant claim 29, 35, and 37). One of ordinary skill in the art would have been motivated to make this modification to facilitate bioanalytical studies.
One of ordinary skill in the art would have also found it prima facie obvious to further add EDTA as a second absorption enhancing compound to obtain a composition comprising insulin and/or FITC-labeled insulin, chenodeoxycholic acid, propyl gallate, and EDTA (reads on instant claims 30 and 38). There is motivation to include two absorption enhancing compounds in a composition because Modi teaches that “orally administered insulin formulation which contains only one absorption enhancer…has very little metabolic effect on the blood glucose levels” (col. 6, lines 50-55). However, when at least two absorption enhancers are in the pharmaceutical composition, “orally administered insulin formulation has a metabolic effect on the blood glucose levels” (col. 6, lines 14-15).
Recall that Modi’s invention encompasses a pharmaceutical composition comprising at least two absorption enhancer compounds: EDTA and chenodeoxycholate (Modi, claim 1). Therefore, a POSITA would further been motivated to combine EDTA with the formulation of New comprising chenodeoxycholic acid with a reasonable expectation of success since chenodeoxycholic acid is very similar in structure with chenodeoxycholate as the former is the free acid form of the latter. One of ordinary skill would have also been motivated to incorporate chenodeoxycholate instead of chenodeoxycholic acid as Modi teaches a pharmaceutical composition comprising the EDTA and chenodeoxycholate instead of the free acid form (Modi, claim 1. See teachings of Modi as discussed in “Rejection – Part 1” for excerpt; Reads on instant claim 34). Therefore, a pharmaceutical composition comprising insulin and/or FITC-labeled insulin, chenodeoxycholic acid or chenodeoxycholate, EDTA, and propyl gallate is obvious to make and reads on instant claims 29, 30, 34, 35, 37, and 38.
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 29-35, 37, and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 3, 4, 6, and 7 of U.S. Patent Application No. 18/273,754 (‘754) in view of Hentz et al. (Hentz) (Hentz, N. G. et al. Synthesis and Characterization of Insulin−Fluorescein Derivatives for Bioanalytical Applications. Anal. Chem. 1997, 69, 4994-5000.) and
claims 1 and 12-14 of U.S. Patent No. 8,314,058 B2 (‘058B2) in view of
Modi et al. (Modi) (US5653987A; published August 5, 1997)
Although the claims at issue are not identical, they are not patentably distinct from each other because there is significant overlap between the instant claims and the three claim sets from the patents or co-pending application.
Regarding Application ‘754, Claims 1-2 are canceled, yet claims 4, 6, and 7 are dependent on claim 1. For this office action, Examiner interprets claims 4, 6, and 7 of ‘754 to be dependent on claim 3 instead. A pharmaceutical composition (herein, referred to as composition-754) comprising EDTA, insulin (a proteinic therapeutic compound like insulin), chenodeoxycholate and propyl gallate is encompassed by claims 3, 4, 6, and 7 of ‘754.
Instant application claims 29, 30, 34, 35, 37, and 38 encompass a pharmaceutical composition (herein, referred to as composition-IA) comprising a bile salt (like chenodeoxycholate), a proteinic therapeutic compound (like insulin), a photochemical internalization agent (like FITC or FITC-insulin), and propyl gallate that is employed in conjunction with EDTA. Composition-IA is substantively the same as composition-754. The only difference between the two compositions is that composition-IA includes the fluorescent labeling of insulin which serves merely to facilitate bioanalytical detection (as taught by Hentz, abstract) and does not add a distinct therapeutic function.
A pharmaceutical composition (herein, referred to as composition-058B2) comprising a bile acid, an active macromolecular principle (i.e., a therapeutic compound), and propyl gallate wherein the composition is coated with an enteric coating which becomes permeable at a pH from 3 to 7 is encompassed by claims 1 and 12-14 of U.S. Patent ‘058B2. Composition-058B2 is also encompassed by instant claim 31.
One of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the claimed invention to add EDTA to composition-058B2, for example, as the second absorption enhancing compound (reads on instant claims 31-33). There is motivation to include two absorption enhancing compounds in a composition because Modi teaches that “orally administered insulin formulation which contains only one absorption enhancer…has very little metabolic effect on the blood glucose levels” (col. 6, lines 50-55). However, when at least two absorption enhancers are in the pharmaceutical composition, “orally administered insulin formulation has a metabolic effect on the blood glucose levels” (col. 6, lines 14-15).
Conclusion
No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM ET.
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/KRISTEN W ROMERO/Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624