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 .
Election/Restrictions
Regarding the restriction requirement, Applicant's election with traverse of the invention of Group I in the reply filed on 6 June 2026 is acknowledged. The traversal is on the ground(s) that the full scope of the invention could be searched and examined without undue burden on the Patent Office. This is not found persuasive. Because the inventions are distinct and have acquired a separate status in the art as demonstrated by their different classification and recognized divergent subject matter, the inventions would require a different field of search including the use of different search queries that is not likely to result in finding art pertinent to the other inventions.
The restriction requirement is still deemed proper and is therefore made FINAL.
Regarding the election of species requirement, Applicants elected, with traverse, the
following species for examination:
PNG
media_image1.png
198
713
media_image1.png
Greyscale
Applicant's election with traverse of the above species requirement in the reply filed on 6 June 2026 is acknowledged. The traversal is on the ground(s) that the full scope of the invention could be searched and examined without undue burden on the Patent Office. This is not found persuasive. Because each species of each Species Group is classified in different, separate areas of the patent classification system, searching the species will require different, non-overlapping search queries.
Applicant is reminded that, upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional corresponding species which are written in dependent form or otherwise require all the limitations of an allowed generic claim. Currently, the following elected claims are generic with respect to the elected species: claims 1 and 44. However, no generic claim has been found allowable. See rejections below.
The election species requirement is still deemed proper and is therefore made FINAL.
Status of Claims
Claims 1, 3-6, 9, 12-14, 16-19, 21-24, 26-28, 44, 89 and 91 are pending. Claim 91 is withdrawn as being drawn to a non-elected invention.
Priority
The instant application claims priority as follows:
PNG
media_image2.png
51
362
media_image2.png
Greyscale
Information Disclosure Statement
All references from the IDS(s) received 12 Jan 2026 and 8 April 2024 have been considered unless marked with a strikethrough.
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 framework for the objective analysis for determining obviousness under 35 U.S.C. 103 is stated in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Obviousness is a question of law based on underlying factual inquiries. The factual inquiries enunciated by the Supreme Court in Graham are summarized as follows:
(A) Determining the scope and content of the prior art;
(B) Ascertaining the differences between the claimed invention and the prior art; and
(C) Resolving the level of ordinary skill in the pertinent art.
Objective evidence relevant to the issue of obviousness must be evaluated by Office personnel. Id. at 17-18, 148 USPQ at 467. The evidence may be included in the specification as filed, accompany the application on filing, or be provided in a timely manner at some other point during the prosecution. The weight to be given any objective evidence is determined on a case-by-case basis. The mere fact that an applicant has presented evidence does not mean that the evidence is dispositive of the issue of obviousness.
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. See MPEP 2143.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation (TSM) in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
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.
Rejections under 35 USC § 103
Claims 1, 3-6, 9, 12-14, 16-19, 21-24, 26-28, 44 and 89 are rejected under 35 U.S.C. 103 as being unpatentable over Sinha et al. (US-20210009525-A1; published 2021-01-14) in view of Collett et al. (US-20200345647-A1; published 2020-11-05) and Dokou et al. (US-20130195797-A1; published 2013-08-01), and further in view of KP Hapgood ("Colloidal Silicon Dioxide" in Handbook of Pharmaceutical Excipients, 6th ed., Pharmaceutical Press, pp. 185-188).
Brief Discussion of Cited References
Sinha et al.
Sinha et al. teach the synthesis of Compound I having the following structure:
PNG
media_image3.png
237
509
media_image3.png
Greyscale
See Example 4, starting at paragraph [0176].
Sinha et al. teach various purified crystalline forms of Compound I, including a purified crystalline acetic acid form of Compound I having an X-ray powder diffraction (XRPD) pattern included peaks at 10.0, 18.1, 18.6, 20.1, and 23.9 degrees, ±0.5, ±0.2, or ±0.1 degrees, 2θ, (Cu Kα radiation). See Example 6, starting at paragraph [0181].
Sinha et al. teach that “Compound 1 is formulated and administered according to methods known in the art. The pharmaceutical compositions containing the active ingredient may be in a form suitable for oral use, for example, as tablets, …” Regarding the tablets for oral use, Sinha et al. teach that “Tablets contain the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients, which are suitable for the manufacture of tablets. These excipients may be for example, inert diluents, such as cellulose, silicon dioxide, aluminum oxide, calcium carbonate, sodium carbonate, glucose, mannitol, sorbitol, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, corn starch, or alginic acid; binding agents, for example PVP, cellulose, PEG, starch, gelatin or acacia, and lubricating agents, for example magnesium stearate, stearic acid or talc.” Emphasis added. See Sinha et al. at paragraph [0144].
Taken together, Sinha et al. teach, among other aspects of the claimed invention, a crystalline acetic acid form of Compound I and the desirability to create dosage forms suitable for oral use comprising the crystalline acetic acid form of Compound I.
Collett et al.
Collett et al. teach an example of an oral solid dosage form comprising:
a) a crystalline kallikrein inhibitor (Compound A) having the following structure:
PNG
media_image4.png
284
513
media_image4.png
Greyscale
which shares structural features with Compound I of the claimed invention,
b) a disintegrant; and
c) a lubricant.
See Collett et al. at Table 9.
Collett et al. teach an example in which the disintegrant is croscarmellose sodium. See Collett et al. at Table 9 and at paragraph [0047]. Collett et al. teach an example in which the lubricant is magnesium stearate. See Collett et al. at Table 9. Collett et al. also teach that lubricant may comprise sodium stearyl fumarate. See Collett et al. at paragraph [0050]. Moreover, Collett et al. teach an optional glidant (flow aid) that may comprise colloidal silicon dioxide. See Collett et al. paragraph [0053].
Collett et al. teach an example tablet comprising Compound A as an active pharmaceutical ingredient (API) and that the tablet comprises 33.33% API by weight. See Collett et al. at Table 9. Collett et al. teach that the solid form of the API may be present in an amount of between about 1 wt % and about 70 wt %, optionally between about 5 wt % and about 60 wt %, or between about 5 wt % and about 50 wt % based on the total weight of the oral solid dosage form. See Collett et al. at paragraph [0040]. Collett et al. teach an example tablet comprising 33.33% API by weight. See Collett et al. at Table 9. Collett et al. teach that the glidant may be present in an amount of between about 0.1 wt % and about 10 wt %. See Collett et al. at paragraph [0055]. Collett et al. teach that the disintegrant may be present in an amount of between about 0.1 wt % or about 50 wt %. See Collett et al. at paragraph [0049]. Collett et al. teach an example tablet comprising 4.00% lubricant by weight. See Collett et al. at paragraph Table 9. Collett et al. teach that the lubricant may be present in an amount of between about 0.1 wt % and about 10 wt %. See Collett et al. at paragraph [0052]. Collett et al. teach the lubricant may be present in an amount of between about 0.1 wt % and about 10 wt %. See Collett et al. at paragraph [0052].
Taken together, Collett et al. teach, among other aspects of the claimed invention, an example of an oral solid dosage form comprising: a kallikrein inhibitor, a disintegrant, and a lubricant. Collett et al. also teach an optional glidant (flow aid).
Dokou et al.
Dokou et al. teach an example of an oral solid dosage form comprising:
a) an active pharmaceutical ingredient (API),
b) colloidal silicon dioxide as the glidant (flow aid),
c) croscarmellose sodium as the disintegrant, and
c) sodium stearyl fumarate as the lubricant.
See Dokou et al. at Tables 7 and11.
Dokou et al. teach an example in which the glidant (flow aid) is colloidal silicon dioxide, the lubricant is sodium stearyl fumarate, and the disintegrant is croscarmellose sodium. See Dokou et al. at Tables 7 and11.
Dokou et al. teach example tablets comprising 51.05% API by weight (Table 6) and 59.56% API by weight (Table 7). Dokou et al. teach that the active ingredient in the formulation can constitute from greater than 0% to about 80% by weight based on the total weight of the formulation. See Dokou et al. at paragraph [0091]. Dokou et al. teach example tablets comprising 51.05% API by weight (Table 6) and 59.56% API by weight (Table 7). Dokou et al. teach example tablets comprising 0.85% glidant by weight (Table 7 and Table 11). Dokou et al. teach that, in one embodiment, the one or more glidants comprises about up to 3% by weight of the pharmaceutical formulation. See Dokou et al. at paragraph [0127]. Dokou et al. teach example tablets comprising 0.85% glidant by weight. See Dokou et al. at Table 7 and Table 11. Dokou et al. teach that, in one embodiment, the one or more glidants comprises about up to 3% by weight of the pharmaceutical formulation. See Dokou et al. at paragraph [0127]. Dokou et al. teach example tablets comprising 4.25% disintegrant by weight (Table 7 and Table 11), which falls within the recite range. Dokou et al. teach that, in some embodiments, the disintegrant component comprises from about 0.5% to about 15% by weight of the pharmaceutical formulation. See Dokou et al. at paragraph [0126]. Dokou et al. teach example tablets comprising 4.25% disintegrant by weight. See Dokou et al. at Table 7 and Table 11. Dokou et al. teach that, in some embodiments, the disintegrant component comprises from about 0.5% to about 15% by weight of the pharmaceutical formulation. See Dokou et al. at paragraph [0126]. Dokou et al. teach example tablets comprising 3.00% lubricant by weight. See Dokou et al. at Table 7 and Table 11. Dokou et al. teach example tablets comprising 3.00% lubricant by weight (Table 9). Dokou et al. teach that, in some embodiments, the one or more lubricant comprises from about 0.5% to about 4% by weight of the pharmaceutical formulation. See Dokou et al. at paragraph [0129].
Taken together, Dokou et al. teach, among other aspects of the claimed invention, an example of an oral solid dosage form comprising: an active pharmaceutical ingredient (API), colloidal silicon dioxide as the glidant (flow aid), croscarmellose sodium as the disintegrant, and sodium stearyl fumarate as the lubricant.
Handbook of Pharmaceutical Excipients
Hapgood teach that, in addition to functioning as a glidant (flow aid), colloidal silicon dioxide also functions as an anticaking (anti-adherent) agent. See KP Hapgood at page 185, second column.
Comparison Between the Claimed Invention and the Prior Art
Relevant to independent claims 1 and 44:
Sinha et al. teach, among other aspects of the claimed invention, a crystalline acetic acid form of Compound I and the desirability to create dosage forms suitable for oral use comprising the crystalline acetic acid form of Compound I.
Collett et al. teach, among other aspects of the claimed invention, an example of an oral solid dosage form comprising a kallikrein inhibitor, croscarmellose sodium as the disintegrant, magnesium stearate as the lubricant. Moreover, Collett et al. teach that sodium stearyl fumarate as an alternative lubricant and teach an optional glidant (flow aid) that comprises colloidal silicon dioxide.
Dokou et al. teach, among other aspects of the claimed invention, an example of an oral solid dosage form comprising an active pharmaceutical ingredient (API), colloidal silicon dioxide as the glidant (flow aid), croscarmellose sodium as the disintegrant, and sodium stearyl fumarate as the lubricant.
Relevant to claim 3, Sinha et al. teach various purified crystalline forms of Compound I, including an acetic acid form. See Example 6, starting at paragraph [0181].
Relevant to claims 4 and 5, Sinha et al. teach a purified crystalline acetic acid form of Compound I having an X-ray powder diffraction (XRPD) pattern included peaks at 10.0, 18.1, 18.6, 20.1, and 23.9 degrees, ±0.5, ±0.2, or ±0.1 degrees, 2θ, (Cu Kα radiation). See Example 6, starting at paragraph [0181]. The crystalline form of Compound I appears to be substantially free of other polymorphic forms of Compound 1.
Relevant to claims 12 and 13, Dokou et al. teach an example in which the glidant (flow aid) is colloidal silicon dioxide. See Dokou et al. at Tables 7 and11. Similarly, Collett et al. teach that an optional glidant (flow aid) may comprise colloidal silicon dioxide. See Collett et al. paragraph [0053].
Relevant to claims 17 and 18, Dokou et al. teach an example in which the disintegrant is croscarmellose sodium. See Dokou et al at Tables 7 and11. Similarly, Collett et al. teach an example in which the disintegrant is croscarmellose sodium. See Collett et al. at Table 9 and at paragraph [0047].
Relevant to claims 22 and 23, Dokou et al. teach an example in which the lubricant is sodium stearyl fumarate. See Dokou et al. at Tables 7 and11. Similarly, Collett et al. that the teach that lubricant may comprise sodium stearyl fumarate. See Collett et al. at paragraph [0050].
Relevant to claims 27, Dokou et al. teach an example in which the glidant (flow aid) is colloidal silicon dioxide, the lubricant is sodium stearyl fumarate, and disintegrant is croscarmellose sodium. See Dokou et al. at Tables 7 and11.
Relevant to claim 28, Dokou et al. teach compositions comprising colloidal silicon dioxide. See Dokou et al. at Tables 7 and11. Similarly, Collett et al. teach a composition comprising colloidal silicon dioxide. See Collett et al. at paragraph [0053]. In addition to functioning as a glidant (flow aid), colloidal silicon dioxide also functions as an anticaking (anti-adherent) agent. See KP Hapgood at page 185, second column.
Regarding claims 6, 9, 14, 16, 19, 21, 24, 26, each claim recites an amount, either by range or specific amount, of a component in the composition for oral delivery. A claimed numerical range that overlaps with, or is close to, a range disclosed in the prior art is presumed to be prima facie obvious through routine experimentation. MPEP § 2144.05. In the instant case, recited amounts either overlap with, or are close to, ranges disclosed in the prior art.
Claims 6 recites that the amount of Compound 1 in said pharmaceutical composition comprises 20% to 70% by weight. Dokou et al. teach example tablets comprising 51.05% API by weight (Table 6) and 59.56% API by weight (Table 7), both of which fall within the recited range. Collett et al. teach an example tablet comprising 33.33% API by weight (Table 9), which also falls within the recited range. Furthermore, Collett et al. teach that the solid form of the API may be present in an amount of between about 1 wt % and about 70 wt %, optionally between about 5 wt % and about 60 wt %, or between about 5 wt % and about 50 wt % based on the total weight of the oral solid dosage form. See Collett et al. at paragraph [0040]. Likewise, Dokou et al. teach that the active ingredient in the formulation can constitute from greater than 0% to about 80% by weight based on the total weight of the formulation. See Dokou et al. at paragraph [0091].
Claim 9 recites that the amount of Compound 1 in said pharmaceutical composition comprises about 50%, 33.3%, or 34.8% by weight. Dokou et al. teach examples tablets comprising 51.05% API by weight (Table 6) and 59.56% API by weight (Table 7), which is close to one of the recited % weight values. Collett et al. teach an example tablet comprising 33.33% API by weight (Table 9), which close to one of the recited % weight values.
Claim 14 recites that the pharmaceutical composition comprises about 0.25% to about 5% of the glidant (flow aid) by weight. Dokou et al. teach example tablets comprising 0.85% glidant by weight (Table 7 and Table 11), which falls within the recited range. Collett et al. teach that the glidant may be present in an amount of between about 0.1 wt % and about 10 wt %. See Collett et al. at paragraph [0055]. Dokou et al. teach that, in one embodiment, the one or more glidants comprises about up to 3% by weight of the pharmaceutical formulation. See Dokou et al. at paragraph [0127].
Claim 16 recites that the pharmaceutical composition comprises about 1.5% of the glidant (flow aid) by weight. Dokou et al. teach example tablets comprising 0.85% glidant by weight (Table 7 and Table 11), which is close to one of the recited % weight values. Collett et al. teach that the glidant may be present in an amount of between about 0.1 wt % and about 10 wt %. See Collett et al. at paragraph [0055]. Dokou et al. teach that, in one embodiment, the one or more glidants comprises about up to 3% by weight of the pharmaceutical formulation. See Dokou et al. at paragraph [0127].
Claim 19 recites that the pharmaceutical composition comprises about 3% to about 15% of the disintegrant by weight. Dokou et al. teach example tablets comprising 4.25% disintegrant by weight (Table 7 and Table 11), which falls within the recite range. Collett et al. teach an example tablet comprising 4.00% disintegrant by weight (Table 9), which falls within the recite range. Collett et al. teach that the disintegrant may be present in an amount of between about 0.1 wt % or about 50 wt %. See Collett et al. at paragraph [0049]. Dokou et al. teach that, in some embodiments, the disintegrant component comprises from about 0.5% to about 15% by weight of the pharmaceutical formulation. See Dokou et al. at paragraph [0126].
Claim 21 recites that the pharmaceutical composition comprises about 7.3% of the disintegrant by weight. Dokou et al. teach example tablets comprising 4.25% disintegrant by weight (Table 7 and Table 11), which is close to the recited % weight value. Collett et al. teach that the disintegrant may be present in an amount of between about 0.1 wt % or about 50 wt %. See Collett et al. at paragraph [0049]. Dokou et al. teach that, in some embodiments, the disintegrant component comprises from about 0.5% to about 15% by weight of the pharmaceutical formulation. See Dokou et al. at paragraph [0126].
Claim 24 recites that the pharmaceutical composition comprises about 0.25% to 5% of the lubricant by weight. Dokou et al. teach example tablets comprising 3.00% lubricant by weight (Table 7 and Table 11), which falls within the recited range. Collett et al. teach an example tablet comprising 4.00% lubricant by weight (Table 9), which falls within the recited range. Collett et al. teach that the lubricant may be present in an amount of between about 0.1 wt % and about 10 wt %. See Collett et al. at paragraph [0052].
Claim 26 recites that the pharmaceutical composition comprises about 2.5% of the lubricant by weight. Dokou et al. teach example tablets comprising 3.00% lubricant by weight (Table 9). Collett et al. teach the lubricant may be present in an amount of between about 0.1 wt % and about 10 wt %. See Collett et al. at paragraph [0052]. Dokou et al. teach that, in some embodiments, the one or more lubricant comprises from about 0.5% to about 4% by weight of the pharmaceutical formulation. See Dokou et al. at paragraph [0129].
Regarding claim 89, the neither Collett et al. nor Dokou et al. teach the particular dissolution profile as claimed by Applicant. However, Collett et al. teach a dissolution test run at 37° C. with paddle speed of 50 rpm. The tested capsules were enterically coated, and thus showed slow dissolution at pH 3. However, at pH 6, disintegration was complete within 19 minutes for one enteric coating, and disintegration was complete within 31-40 minutes for another enteric coating. The dissolution profile in a drug composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the dissolution profile in order to best achieve the desired results, such as the dissolution profile required by the Food and Drug Administration. Thus, absent some demonstration of unexpected results from the claimed parameters, this optimization of ingredient amount would have been obvious at the time of Applicant's invention.
Differences Between the Claimed Invention and the Prior Art
Sinha et al. do not teach an oral solid dosage form as a unitary example. Neither Collett et al. nor Dokou et al. teach an oral solid dosage form comprising the particular crystallized kallikrein inhibitor recited for the current invention.
Conclusion of Obviousness
At the time of filing, it would have been obvious to create compositions for oral delivery as encompassed by claims 1, 3-6, 9, 12-14, 16-19, 21-24, 26-28, 44 and 89.
Sinha et al. teach, among other aspects of the claimed invention, a crystalline acetic acid form of Compound I and the desirability to create dosage forms suitable for oral use comprising the crystalline acetic acid form of Compound I. Collett et al. teach, among other aspects of the claimed invention, an example of an oral solid dosage form comprising a kallikrein inhibitor, croscarmellose sodium as the disintegrant and magnesium stearate as the lubricant. Moreover, Collett et al. teach that sodium stearyl fumarate as an alternative lubricant and teach colloidal silicon dioxide as an optional glidant (flow aid). Dokou et al. teach, among other aspects of the claimed invention, an example of an oral solid dosage form comprising an active pharmaceutical ingredient (API), colloidal silicon dioxide as the glidant (flow aid), croscarmellose sodium as the disintegrant, and sodium stearyl fumarate as the lubricant.
Sinha et al., Collett et al., and Dokou et al. each teach a finite number of identified components for use in creating the claimed compositions.
At the time of filing, it would have been obvious to substitute the crystalline acetic acid form of Compound I taught by Sinha et al. in place of the API taught by Dokou et al., thereby arriving at the claimed invention. Motivation to do is provided by Sinha et al., who teach the desirability to create dosage forms suitable for oral use comprising the crystalline acetic acid form of Compound I. A reasonable expectation of success is provided by Collett et al., who teach creating an oral dosage form using (i) a crystalline kallikrein inhibitor that is structurally similar to the crystalline acetic acid form of Compound I taught by Sinha et al., and (ii) a formulation that is compositionally similar to the formulation taught by Dokou et al.
Conclusion
No claim is currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRADLEY S MAYHEW whose telephone number is
571-272-8428. The examiner can normally be reached Mon-Fri, 11:00 AM-7:00 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, CLINTON A BROOKS can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/BSM/ Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
Prosecution Insights