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 .
Priority
The instant application claims priority to 371 National Stage Application PCT/IB2023/051570, filed February 21st, 2023, under 35 U.S.C. 119(a)-(d), and claims benefit to provisional application 63312623, filed February 22nd, 2022, under 35 U.S.C.119 (e). The priority date of February 22nd, 2022 is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) filed on November 19th, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is considered by the examiner.
Claims Status
The claims listing filed on April 9th, 2025 is pending. Claims 1-5, 7-10, 13-15, 17, 21-26, and 30 are being examined on the merits in this office action.
Claim Objections
Claims 14-15 are objected to because of the following informalities: Bullet points a)-d) should be followed by a lowercase, not uppercase letter, and should all have a semicolon at the end of the bullet points. Appropriate correction is required.
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 2, 4-5, 7, 10, 14-15, 24-26 and 30 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 2 recites a method of claim 1, characterized by a WAXS spectrum “which includes a peak at 0.12 and 0.23 Å-1. However, the method of claim 1 includes a peak at a region of 0.1 to 0.15 Å-1. It is unclear whether claim 2’s limitation refers to peaks within the same region as claim 1’s limitation, or additional peaks. If it is the former, then claim 2 would qualify as an improper dependent claim because 0.23 Å-1 is not within 0.1-0.15 Å-1. If it is the latter, the rejection may be overcome by using the phrase “includes an additional peak.” Thus, claim 2 is indefinite because it is unclear what WAXS spectrum Form A sodium caprate is characterized by.
Claims 4 and 14-15 recites “an X-ray powder diffraction (XRPD) spectrum which includes a peak at 4° 2Θ.” However, the limitation reciting a scattering angle (2Θ) is indefinite because a scattering angle in X-ray diffraction is dependent on the wavelength of the x-ray beam.
(XRD Basics. (2023, September 4). UPenn Physics https://www.physics.upenn.edu/ ~heiney/datasqueeze/basics.html)
UPenn Physics explains:
In its most simplified form, a generic X-ray scattering measurement is shown below.
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A beam of X-rays is directed towards a sample, and the scattered intensity is measured as a function of outgoing direction. By convention, the angle between the incoming and outgoing beam directions is called 2θ. For the simplest possible sample, consisting of sheets of charge separated by a distance d, constructive interference (greater scattered intensity) is observed when Bragg's Law is satisfied:
n λ = 2 d sin θ
Here n is an integer (1, 2, 3, ...), λ is the wavelength of the x-ray beam, and θ is half the scattering angle 2 θ shown above [What is X-ray diffraction].
Therefore, a claim limitation defined by the scattering angle is not a definite limitation because it is dependent on the wavelength used during measurement and that wavelength is variable in Bragg’s Law.
The term “about” in claim 5, 7, 10, 24-26, and 30 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The specification states that “the term "about" is used to indicate that a value includes the inherent variation of error for the method/device being employed to determine the value, or the variation that exists among the study subjects. Typically, the term "about" is meant to encompass approximately or less than 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19% or 20% variability, depending on the situation” [0052].
In determining the range encompassed by the term "about," one must consider the context of the term as it is used in the specification and claims of the application. Ortho-McNeil Pharm., Inc. v. Caraco Pharm. Labs., Ltd., 476 F.3d 1321, 1326, 81 USPQ2d 1427, 1432 (Fed. Cir. 2007) [MPEP 2173.05(b)].
The specification does not provide a fixed definition or clarify what an “inherent variation of error” is and what range that encompasses. Thus, claims 5, 7, 10, 24-26, and 30 are indefinite because one of ordinary skill in the art cannot ascertain what the claim’s limitations include.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 4-5, 7-10, 21-26, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Khedkar et al (US9241908B2; published 2016) in view of Burnier et al (US8080562B2; published 2011), as evidenced by Diamond (WAXS: Wide angle x-ray scattering. (2020). Diamond Light Source https://www.diamond.ac.uk/Instruments/Techniques/Scattering/WAXS.html)
Khedkar et al. disclose the process of preparing formulations permitting ingestion via oral delivery of proteins/peptides or their conjugates, and/or cation-insulin conjugate complexes, such as IN105, for diabetes [Abstract]. Khedkar et al. claim:
A process for manufacturing an orally administrable tablet pharmaceutical composition of IN105, comprising about 0.01%-20% w/w of IN-105, about 10%-60% w/w of saturated or unsaturated C4-C12 fatty acids, fatty acid esters or salts thereof, 0.01%-5% of binder, 10%-60% w/w of a diluent, 1%-20% w/w of disintegrant, 0.5% w/w of a lubricant and optionally including binders, plasticizers, permeation enhancers and solubilizers, wherein the lubricant is magnesium stearate, the method comprising the steps of:
a. grinding suitable saturated or unsaturated C4-C12 fatty acids and/or salts of such fatty acid and a binder;
b. suspending the cation-insulin conjugate complex in an organic solvent using the binder to form a wet mass;
c. granulation of the components obtained from step (b) using the binder to form dried granules;
d. rasping the dried granules of step (c);
e. blending the dried granules with other excipients; and
f. compressing the blended mixture for tablet formation [claim 9].
Khedkar et al. teach the fatty acid to be sodium caprate [claims 24 and 27]. Khedkar et al. do not teach the sodium caprate to be Form A sodium caprate.
Burnier et al. teach various crystalline Forms A-E of formula I, an inhibitor of lymphocyte function-associated antigen-1, differentiated and characterized by their X-ray powder diffraction pattern peaks at a reflection angle 2Θ [Col 1 line 27 and Col 2].
The method of producing crystalline Form A removes more impurities that were introduced to the compound of Formula I throughout the synthetic route, which may be due to one or more of by-products of the synthesis, impurities introduced with reagents used in the synthesis, trapped organic solvents used in prior reaction steps, such as methylene chloride, and contaminants due to degradation of an intermediate product of the synthetic sequence…Additionally, the level of methylene chloride must be lower than that permitted by the FDA guidelines. [Col 20 line 29].
Thus, Burnier et al. motivate one of ordinary skill in the art to use a Form A crystalline structure in a method of making a pharmaceutical composition to remove impurities and follow FDA guidelines. Khedkar and Burnier et al. do not teach characterization of Form A sodium caprate by WAXS.
Diamond evidences that,
Wide Angle X-ray Scattering (WAXS) is a technique used for the investigation of partially ordered materials. It is often employed to characterize the crystalline structure of polymers, by measuring the interatomic spacings within the unit cell. It is sub-nanometre-sized structures within the sample that cause the wide angles [pgh 1].
Thus, the WAXS spectrum of Form A sodium caprate is characteristic of the interatomic spacings that make up its crystalline structure.
The discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999) [MPEP 2112 (I)].
The discovery that Form A sodium caprate is characterized by a WAXS spectrum which includes a peak at a region of 0.1-0.15 Å-1 does not render the teachings of Khedkar et al. in view of Burnier et al. patentably new because when sodium caprate has a Form A crystalline structure, it can be characterized as such.
Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim, but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103 [MPEP 2112 (III)].
Therefore, prior to the effective filing date, it would have been obvious to use Khedkar et al’s method to make an oral tablet and use Form A sodium caprate as the fatty acid because Burnier et al. motivates using Form A crystalline structures to obtain a purer product.
Regarding claim 2, "the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). [MPEP 2112 (I)]. The discovery that Form A sodium caprate is characterized by WAXS spectrum which includes a peak at 0.12 and 0.23 Å-1 does not render the teachings of Khedkar et al. in view of Burnier et al. patentably new because when sodium caprate has a Form A crystalline structure, it can be characterized by such a WAXS spectrum.
Regarding claim 4, Burnier et al’s Formula I in Form A is characterized by an X-ray powder diffraction pattern having peaks at a reflection angle 2Θ of about 18.2, 21.4. and 22.7 degrees. This goes to show that the XRPD spectrum peaks dependent on the crystalline form and type of substance and are an inherent property. ” Also, Diamond evidences that “WAXS, essentially analogous to powder diffraction, provides information about crystallization and can be measured simultaneously with SAXS” [pgh 2]. “The discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). [MPEP 2112 (I)]. The discovery that Form A sodium caprate is characterized by XRPD spectrum which includes a peak at 4° 2Θ does not render the teachings of Khedkar et al. in view of Burnier et al. patentably new because when sodium caprate has a Form A crystalline structure, it can be characterized by such a XRPD spectrum
Regarding claim 5, in one of Khedkar et al.’s embodiments, it is specified that the moisture content of the granules-which are made of sodium caprate- is 1.99% [Col 25 line 37]. Furthermore, “where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim, but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103” [MPEP 2112 (III)]. The water content of Form A sodium caprate is inherent to its crystalline structure and therefore not patentably distinct from Khedkar et al’s method in view of Burnier et al.
Regarding claim 7, in one of Khedkar et al.’s embodiments, it is specified that the moisture content of the granules, made of sodium caprate, is 1.99% [Col 25 line 37]. This is about 1.5%. Also “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close” because when the proportions are close one skilled in the art would expect the instant invention to have the same properties [Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) and MPEP 2144.05]. Thus, it is prima facie obvious to use a Form A crystalline sodium caprate in Khedkar et al’s process where the granulation comprising sodium caprate has a moisture content of about 1.5%.
Furthermore, where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim, but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103” [MPEP 2112 (III)]. The water content of Form A sodium caprate is inherent to its crystalline structure and therefore not patentably distinct from Khedkar et al’s method in view of Burnier et al.
Regarding claim 8, Khedkar et al. specify that milled sodium caprate is used before compressing their invention into a tablet [Col 27 Example 2].
Regarding claim 9, Khedkar et al. specify that granules comprising the IN-105 peptide and sodium caprate were passed through a 14# sieve before compressing their invention into a tablet [Col 27 Example 2].
Regarding claim 10, Khedkar et al. specify a process of manufacture, that includes the rasping of dried sodium caprate granules through 45# sieve before tablet compression where sodium caprate has a particle size of 355 μm, within the instant range of about 35 μm to about 1300 μm [Col 22 line 33].
Regarding claims 21-23, Khedkar et al. specify that Formulation 862 is prepared by direct compression and comprises of sodium caprate and mannitol [Col 39 line 37 and Col 25 line 5].
Regarding claim 24, the process for manufacturing an orally administrable tablet pharmaceutical composition of IN105 comprises about 0.01%-20% w/w of IN-105, encompassing the instant range [claim 9].
Regarding claim 25, the process for manufacturing an orally administrable tablet pharmaceutical composition of IN105 comprises about 10%-60% w/w of saturated or unsaturated C4-C12 fatty acids, overlapping with the instant range, and the fatty acid is taught to be sodium caprate [claim 9 and 24].
Regarding claim 26, the process for manufacturing an orally administrable tablet pharmaceutical composition of IN105 comprises about 10%-60% w/w of a diluent, overlapping with the instant range, and the diluent is taught to be mannitol.
Regarding claim 30, a preparation specified by Khedkar et al. comprising mixing sodium caprate and IN-105 and compression had a tensile hardness of 1.38-1.58 kg/cm2, the equivalent of 0.1353318- 0.1549451 MPa [Col 35 and 36].
.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Khedkar et al in view of Burnier et al and evidenced by Diamond, as applied to claims 1-2, 4-5, 7-9, 21-26, and 30, further evidenced by Xenocs (What is SAXS? (2026, January 13). Xenocs. https://www.xenocs.com/saxs-basics/).
Khedkar et al, Burnier et al, and Diamond do not evidence the role of SAXS. Xenocs evidence that “small-Angle X-ray Scattering (SAXS) is a common technique for characterizing materials at the nanometer and mesoscale levels. Specifically, SAXS analyzes X-ray scattering at very small angles to reveal the size, shape, and internal structure of nanostructures” [pgh 1]. Thus, the SAXS spectrum is characteristic of the internal crystalline structure of Form A sodium caprate.
The discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). [MPEP 2112 (I)].
The discovery that Form A sodium caprate is characterized by SAXS spectrum which includes a peak at 0.12 and 0.23 Å-1 does not render the teachings of Khedkar et al. in view of Burnier et al. patentably new because when sodium caprate has a Form A crystalline structure, it can be characterized as such.
Claims 1-2, 4-5, 7-10, 13, 17, and 21-26, are rejected under 35 U.S.C. 103 as being unpatentable over Coughlan et al (US20110182985A1) in view of Burnier et al (US8080562B2; published 2011), as evidenced by Diamond (WAXS: Wide angle x-ray scattering. (2020). Diamond Light Source https://www.diamond.ac.uk/Instruments/Techniques/Scattering/WAXS.html)
Coughlan et al. claim a method of providing a pharmaceutical composition for oral administration in a single dosage unit with a patient acceptable size, wherein the composition comprises:
(i) a therapeutically effective amount of a therapeutically active ingredient;
(ii) at least one water soluble enhancer; and
(iii) a saccharide;
the method comprising directly compressing or dry granulating the enhancer without adding any moisture agent before preparing the dosage form [claim 14]. Coughlan et al. claim the water-soluble enhancer to be sodium caprate and specify that the therapeutically active ingredient may be a peptide or protein active ingredient [claim 39 and 0084]. The specific procedure taught using the peptide octreotide comprises:
(i) Dispensing
Sodium caprate and octreotide acetate and Parteck SI 150 (sorbitol) were screened through a 355 μm mesh into a stainless steel base pan. These materials were then transferred to a plastic container and blended together for 5 minutes. The stearic acid was then screened through a 355 μm mesh and added to the blended materials and blended for a further 2 minutes.
(ii) Tableting
The blended materials were then weighed out into lots of 700 mg and compressed at a PSI 4500 on a MTCM-I single punch tablet press fitted with a 16×8 mm oval shaped tool. The average hardness was 103 N and average weight was 699 mg. 60 tablets were compressed in total. These tablets were placed into Duma bottles and stored in the freezer overnight. The tablets were removed from the freezer and allowed to equilibrate to room temperature
(iii) Film Coating (Sub)
51.34 g of Opadry I1 yellow 85F32410 and 205.26 ml of purified water was dispensed and mixed together for 40 minutes at high-speed using a IKA stirrer. After 40 minutes the solution was screened through a 90 μm mesh. Both the bulking Placebo cores and Octreotide Acetate tablets were placed into the O'Hara Labcoat M and the tablets were coated with the weight gain of approximately 4.5% weight gain using the following parameters. [0118-0121].
Coughlan et al. do not teach the sodium caprate to be Form A sodium caprate.
Burnier et al. teach various crystalline Forms A-E of Formula I, an inhibitor of Lymphocyte Function-Associated Antigen-1, differentiated and characterized by their X-ray powder diffraction pattern peaks at a reflection angle 2Θ [Col 1 line 27 and Col 2].
The method of producing crystalline Form A removes more impurities that were introduced to the compound of Formula I throughout the synthetic route, which may be due to one or more of by-products of the synthesis, impurities introduced with reagents used in the synthesis, trapped organic solvents used in prior reaction steps, such as methylene chloride, and contaminants due to degradation of an intermediate product of the synthetic sequence…Additionally, the level of methylene chloride must be lower than that permitted by the FDA guidelines. [Col 20 line 29].
Thus, Burnier et al. motivate one of ordinary skill in the art to use a Form A crystalline structure in a method of making a pharmaceutical composition to remove impurities and follow FDA guidelines. Coughlan and Burnier et al. do not teach characterization of Form A sodium caprate by WAXS.
Diamond evidences that,
Wide Angle X-ray Scattering (WAXS) is a technique used for the investigation of partially ordered materials. It is often employed to characterise the crystalline structure of polymers, by measuring the interatomic spacings within the unit cell. It is sub-nanometre-sized structures within the sample that cause the wide angles [pgh 1].
Thus, the WAXS spectrum of Form A sodium caprate is characteristic to its interatomic spacings that make up its crystalline structure.
The discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999) [MPEP 2112 (I)].
The discovery that Form A sodium caprate is characterized by a WAXS spectrum which includes a peak at a region of 0.1-0.15 Å-1 does not render the teachings of Khedkar et al. in view of Burnier et al. patentably new because when sodium caprate has a Form A crystalline structure, it can be characterized as such.
Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim, but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103 [MPEP 2112 (III)].
Therefore, prior to the effective filing date, it would have been obvious to use Coughlan et al’s method to make an oral tablet and use Form A sodium caprate as the water soluble enhancer because Burnier et al. motivates using Form A crystalline structures to obtain a purer product.
Regarding claim 2, "the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). [MPEP 2112 (I)]. The discovery that Form A sodium caprate is characterized by WAXS spectrum which includes a peak at 0.12 and 0.23 Å-1 does not render the teachings of Coughlan et al. in view of Burnier et al. patentably new because when sodium caprate has a Form A crystalline structure, it can be characterized as such.
Regarding claim 4, Burnier et al’s Formula I in Form A is characterized by an X-ray powder diffraction pattern having peaks at a reflection angle 2Θ of about 18.2, 21.4. and 22.7 degrees. This goes to show that the XRPD spectrum peaks dependent on the crystalline form and type of substance and are an inherent property.” Also, Diamond evidences that “WAXS, essentially analogous to powder diffraction, provides information about crystallization and can be measured simultaneously with SAXS” [pgh 2]. “The discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). [MPEP 2112 (I)]. The discovery that Form A sodium caprate is characterized by XRPD spectrum which includes a peak at 4° 2Θ does not render the teachings of Coughlan et al. in view of Burnier et al. patentably new because when sodium caprate has a Form A crystalline structure, it can be characterized as such.
Regarding claim 5, “where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim, but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103” [MPEP 2112 (III)]. The water content of Form A sodium caprate is inherent to its crystalline structure and therefore not patentably distinct from Coughlan et al’s method in view of Burnier et al.
Regarding claim 7, “where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim, but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103” [MPEP 2112 (III)]. The water content of Form A sodium caprate is inherent to its crystalline structure and therefore not patentably distinct from Coughlan et al’s method in view of Burnier et al.
Regarding claim 8, in the procedure taught by Coughlan et al, sodium caprate and octreotide acetate and Parteck SI 150 (sorbitol) are screened through a 355 μm mesh into a stainless-steel base pan before compression [0119]. Thus, Coughlan et al. teach sieving sodium caprate before compression.
Regarding claim 9, in the procedure taught by Coughlan et al, sodium caprate and octreotide acetate and Parteck SI 150 are screened through a 355 μm mesh into a stainless-steel base pan before compression [0119]. Thus, Coughlan et al. teach sieving a mixture comprising sodium caprate before compression.
Regarding claim 10, in the procedure taught by Coughlan et al, sodium caprate is screened through a 355 μm mesh before compression, which means it has a particle size of 355 μm, encompassed by the instant range [0119].
Regarding claim 13, in the procedure taught by Coughlan et al, a film coating is formed after the blended materials are compressed [0118-0121].
Regarding claim 17, in the procedure taught by Coughlan et al, compression is performed at a PSI 4500, the equivalent of 31 MPa [0119].
Regarding claims 21-22, the dispensing step comprises blending sodium caprate, octreotide acetate, and sorbitol together.
Regarding claim 23, the method taught by Coughlan et al. uses sorbitol not mannitol. However, Coughlan et al. claim that in some embodiments, the saccharide can also be mannitol [claim 20]. It is obvious to one of ordinary skill in the art to substitute one known element for another to obtain predictable results because both sorbitol and mannitol are saccharides that act as diluents [0065].
Regarding claim 24, Coughlan et al’s specific procedure results in 8.95 mg of octreotide in a tablet with a total weight of 797.335 mg. This translates to 1.12% by weight of peptide, within the instant range [0114].
Regarding claim 25, Coughlan et al’s specific procedure results in 550 mg of sodium caprate in a tablet with a total weight of 797.335 mg. This translates to 69.0% by weight, within the instant range [0114].
Regarding claim 26, Coughlan et al’s specific procedure results in 136.5 mg of Parteck SI 150 (sorbitol) in a tablet with a total weight of 797.335 mg. This translates to 17.1% by weight of polyol, within the instant range [0114].
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Coughlan et al in view of Burnier et al and evidenced by Diamond, as applied to claims 1-2, 4-5, 7-9, 21-26, and 30, further evidenced by Xenocs (What is SAXS? (2026, January 13). Xenocs. https://www.xenocs.com/saxs-basics/).
Coughlan et al, Burnier et al, and Diamond do not evidence the role of SAXS. Xenocs evidence that “Small-Angle X-ray Scattering (SAXS) is a common technique for characterizing materials at the nanometer and mesoscale levels. Specifically, SAXS analyzes X-ray scattering at very small angles to reveal the size, shape, and internal structure of nanostructures” [pgh 1]. Thus, the SAXS spectrum is characteristic of the internal crystalline structure of Form A sodium caprate.
The discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). [MPEP 2112 (I)].
The discovery that Form A sodium caprate is characterized by SAXS spectrum which includes a peak at 0.12 and 0.23 Å-1 does not render the teachings of Coughlan et al. in view of Burnier et al. patentably new because when sodium caprate has a Form A crystalline structure, it can be characterized as such.
Claims 14 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Coughlan et al in view of Burnier et al and evidenced by Diamond, as applied to claims 1-2, 4-5, 7-9, 21-26, and 30, further in view of Khedkar et al.
Regarding claim 14, Coughlan et al. teach the preparation of tablets by wet granulation:
A dry powder mixture of sodium caprate, mono sodium alendronate trihydrate, and PVP K30 was granulated using a 25-percentage solution. The granulate was then screened and subsequently fluid bed dried and milled. Then, granulates were blended with aerosol, mannitol, polyplasdone, and stearic acid. The blended mixture was compressed and subcoated. Finally, the mixture was enteric coated [0091].
The active ingredient is alendronate, which is a small molecule drug, not a peptide. However, Coughlan et al. state that the therapeutically active ingredient may be a peptide or protein active ingredient [0087]. Thus, Coughlan et al. teach
wet granulating sodium caprate, a peptide, and PVP K30 to form granules;
drying and milling the granules;
mixing the resulting granules with aerosol, mannitol, polyplasdone, and stearic acid;
compressing the mixture to form a tablet.
Coughlan et al. do not teach wet granulating sodium caprate before mixing it with a peptide, using a non-aqueous organic solvent while wet granulating, and that sodium caprate is Form A sodium caprate characterized by a WAXS spectrum which includes a peak at a region of 0.1-0.15 Å-1 or an XRPD spectrum which includes a peak at 4° 2Θ. Burnier et al. motivates one of ordinary skill in the art to use Form A sodium caprate and Diamond evidence that a WAXS and XRPD spectrum are inherent to the crystalline structure of a compound (see claim 1 and 4 rejection).
Khedkar et al. also teach a method of making a tablet using wet granulation:
Drug formulations in accordance with the present invention were prepared and tested. Accordingly, required amount of ground Sodium caprate was weighed accurately into a planetary mixture and the granulate with 700 ml of isopropyl alcohol. The amount of isopropyl alcohol added to convert the powder mixture to granular form was calculated. The wet mass was scraped every 5 minutes, such that the mixture does not stick to the wall of the planetary mixture. The wet mass was passed through 18# sieve in a wet granulator and air dried overnight under the hood.
Appropriate quantity of IN-105, sodium caprate granules, Kollidon CL and pearlitol was weighed and passed through a 60# sieve and mixed in a double cone blender for 20 minutes at a speed of 12 r.p.m. After homogenous mixing for 20 minutes, the blend was lubricated with aerosol and magnesium stearate for 3 minutes at a speed of 88-90 r.p.m [Col 25-26].
Thus, Khedkar et al. teach using a non-aqueous organic solvent, isopropyl alcohol, to form granules and mixing in the IN-105 peptide after wet granulating sodium caprate to form granules. Khedkar et al. also teach wet granulating sodium caprate alone.
Therefore, prior to the effective filing date, one of ordinary skill in the art would find it obvious to try components from Khedkar et al.’s method in Coughlan et al.’s method and use Form A sodium caprate for a reasonable expectation of successfully making a purer oral tablet.
Regarding claim 15, Coughlan et al. teach the preparation of tablets by wet granulation:
A dry powder mixture of sodium caprate, mono sodium alendronate trihydrate, and PVP K30 was granulated using a 25-percentage solution. The granulate was then screened and subsequently fluid bed dried and milled. Then, granulates were blended with aerosol, mannitol, polyplasdone, and stearic acid. The blended mixture was compressed and subcoated. Finally, the mixture was enteric coated [0091].
The active ingredient is alendronate, which is a small molecule drug, not a peptide. However, Coughlan et al. state that the therapeutically active ingredient may be a peptide or protein active ingredient [0087]. Thus, Coughlan et al. teach
wet granulating sodium caprate, a peptide, and PVP K30 to form granules;
drying and milling the granules;
mixing the resulting granules with aerosol, mannitol, polyplasdone, and stearic acid;
compressing the mixture to form a tablet.
Coughlan et al. does not teach wet granulating sodium caprate before mixing it with a peptide, using a non-aqueous organic solvent while wet granulating, and that sodium caprate is Form A sodium caprate characterized by an XRPD spectrum which includes a peak at 4° 2Θ. Burnier et al. motivates one of ordinary skill in the art to use Form A sodium caprate and Diamond evidence that a XRPD spectrum is inherent to the crystalline structure of a compound (see claim 1 and 4 rejection).
Khedkar et al. also teach a method of making a tablet using wet granulation:
Drug formulations in accordance with the present invention were prepared and tested. Accordingly, required amount of ground Sodium caprate was weighed accurately into a planetary mixture and the granulate with 700 ml of isopropyl alcohol. The amount of isopropyl alcohol added to convert the powder mixture to granular form was calculated. The wet mass was scraped every 5 minutes, such that the mixture does not stick to the wall of the planetary mixture. The wet mass was passed through 18# sieve in a wet granulator and air dried overnight under the hood.
Appropriate quantity of IN-105, sodium caprate granules, Kollidon CL and pearlitol was weighed and passed through a 60# sieve and mixed in a double cone blender for 20 minutes at a speed of 12 r.p.m. After homogenous mixing for 20 minutes, the blend was lubricated with aerosol and magnesium stearate for 3 minutes at a speed of 88-90 r.p.m [Col 25-26].
Thus, Khedkar et al. teach using a non-aqueous organic solvent, isopropyl alcohol, to form granules and mixing in the IN-105 peptide after wet granulating sodium caprate to form granules.
Therefore, prior to the effective filing date, one of ordinary skill in the art would find it obvious to try components from Khedkar et al.’s method in Coughlan et al.’s method and use Form A sodium caprate for a reasonable expectation of successfully making a purer oral tablet.
Conclusion
Claims 14-15 are objected to. Claims 2, 4-5, 7, 10, 14-15, 24-26 and 30 are rejected under 35 U.S.C. 112(b). Claims 1-5, 7-10, 13-15, 17, 21-26, and 30 are rejected under 35 U.S.C. 103.
Correspondence
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/SACHI JAUHARI/ Examiner, Art Unit 1654
/LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654
