Prosecution Insights
Last updated: April 19, 2026
Application No. 18/646,220

CRYSTALLINE FORMS OF (S)-5-BENZYL-N-(5-METHYL-4-OXO-2,3,4,5-TETRAHYDROPYRIDO [3,2-B][1,4]OXAZEPIN-3-YL)-4H-1,2,4-TRIAZOLE-3-CARBOXAMIDE

Non-Final OA §102§103
Filed
Apr 25, 2024
Examiner
COLEMAN, BRENDA LIBBY
Art Unit
1624
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Denali Therapeutics Inc.
OA Round
1 (Non-Final)
75%
Grant Probability
Favorable
1-2
OA Rounds
2y 7m
To Grant
90%
With Interview

Examiner Intelligence

Grants 75% — above average
75%
Career Allow Rate
1201 granted / 1604 resolved
+14.9% vs TC avg
Strong +15% interview lift
Without
With
+15.4%
Interview Lift
resolved cases with interview
Typical timeline
2y 7m
Avg Prosecution
46 currently pending
Career history
1650
Total Applications
across all art units

Statute-Specific Performance

§101
1.5%
-38.5% vs TC avg
§103
5.8%
-34.2% vs TC avg
§102
16.9%
-23.1% vs TC avg
§112
52.3%
+12.3% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1604 resolved cases

Office Action

§102 §103
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 . Claims 21-34 are pending in this application. 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. Claim(s) 21-34 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Estrada et al., WO 2017/136727 (U.S. equivalent) U.S. Patent No. 9,896,458. Estrada teaches the pharmaceutical composition and the process of preparing the pharmaceutical composition where the compound is (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido[3,2-b][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide. As noted in the parent application the compound (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido[3,2-b][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide but are silent on the particular crystallographic form. MPEP 2112 states: “SOMETHING WHICH IS OLD DOES NOT BECOME PATENTABLE UPON THE DISCOVERY OF A NEW PROPERTY The claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).” In this case, the “unknown property” is the particular crystalline form. This is unknown because the reference is silent on this property. MPEP 2112 goes on to state: “A REJECTION UNDER 35 U.S.C. 102/103 CAN BE MADE WHEN THE PRIOR ART PRODUCT SEEMS TO BE IDENTICAL EXCEPT THAT THE PRIOR ART IS SILENT AS TO AN INHERENT CHARACTERISTIC 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, expressed as a 102/103 rejection.” Again, the “CHARACTERISTIC” which the prior art is silent on is the crystalline form (crystalline form is considered to be in the category of chemical properties; see Zenith Laboratories Inc. v. Bristol-Myers Squibb Co. 30 USPQ2d 1285, 1288). This is not an ordinary inherency situation where it is not explicitly stated what the product actually is. In every reference applied, the reference explicitly teaches exactly what the compound is. In fact, it is the opposite. In a normal inherency situation, the claim is of known structure, and the reference is of unknown structure. Here, the latter is not true, and hence the legal circumstances of inherency in the prior art do not apply. The only difference is the property about which the reference happens to be silent. Recitation of a property, inherently possessed by the prior art thing, does not distinguish a claim drawn to those things from the prior art, In re Swinehart, 169 USPQ 226, 229. See for example Ex parte Anderson, 21 USPQ 2d 1241 at 1251, discussion of Rejection E. The claims had “numerical or functional values for certain properties which [the authors of the references] did not measure”. The PTO presented no reasoning as to why the prior art material would have been expected to have those properties. Instead, the decision states, “There is ample precedent for shifting the burden to an applicant to reproduce a prior art product whose final structure or properties are, at least, in part determined by the precise process used in its manufacture.” (page 1253). In another example, certain claims of Ex parte Raychem Corp. 25 USPQ2d 1265 required a linearity ratio of less than 1.2. The decision notes that neither reference discloses any values of the linearity ratio. The PTO presented no reasoning as to what the ratio would be expected to be in the references. The Decision states: “However, this does not end the inquiry since, where the Patent and Trademark Office is not equipped to perform the needed testing, it is reasonable to shift the burden of proof to Raychem to establish that (1) the argued difference exists….” And indeed, there have been a number of cases in which applicants have pointed to silence of the prior art with regard to this or that property: In re Pearson, 181 USPQ 641; In re Zierden 162 USPQ 102; In re Lemin, 140 USPQ 273; Titanium Metals Corporation of America v. Banner, 227 USPQ 773; In re Benner, 82 USPQ 49; In re Wilder, 166 USPQ 545; Ex parte Kucera, 165 USPQ 332; General Electric Co. v. Jewel Incandescent Lamp Co., 67 USPQ 155; In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607; In re Parker, 43 USPQ 457. Such efforts to avoid anticipation on that basis invariably failed. Going further, if silence about properties of prior art compounds could be relied on, then one could not reject over references with no utility (see In re Schoenwald, 22 USPQ2d 1671), since applicants could always insert the utility into the claim as a property. It is well settled that the PTO can require an applicant to establish that a prior art product does not necessarily possess the characteristics of the claimed product when the prior art and claimed products are identical or substantially identical. An applicant's burden under these circumstances was described in In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-434 (CCPA 1977) as follows: Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. . . . Whether the rejection is based on ‘inherency' under 35 U.S.C. § 102, or ‘prima facie obviousness’ under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products (footnote omitted). Overcoming the rejection is very straightforward. One simply replicates the prior art procedure. If the claimed characteristic does not appear at all in the product, or if on repetition, it sometimes does not appear in the product, then the rejection is overcome. If applicants reasoning were accepted, an old compound could always be re-patented, by the simple expedient of isolating the compound in a different manner. All such would be patentee would need to do is attach some parameter which the original patent had been silent about, and there will almost always be such a parameter. For example, suppose a person were to use some solvent anti-solvent pair which applicants didn’t happen to use, and obtained one of applicants’ forms. The person would then write the claim for the compound, using some parameter which applicants didn’t happen to mention, such as density. According to applicants reasoning, the different method of crystallization, along with the instant specification’s silence on density, should prevent any anticipation rejection. The next person could come around with yet another solvent/anti-solvent pair (or some other method) which happened to produce the same form, and this time label it with the gross crystalline habit (e.g. flakes, needles, dendritic, cubic, etc.), which neither of the previous two patentees had mentioned. The fourth inventor could again re-patent the same material, this time tacking on a melting point limitation, pointing to the different method and silence on this characteristic, and the fifth inventor could label the form by refractive index (or dielectric constant), and the sixth could use the enthalpy of melting (i.e. latent heat of melting or “heat of fusion”). Yet another person could specify the maximum level of water or some other solvent, unreacted starting material, or indeed any impurity, previously known or unknown, which the reference happened to be silent about. Additionally, it has been explained that the pharmaceutical composition of a crystalline forms A and B of (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido[3,2-b][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide would lose its crystalline form upon being combined with a pharmaceutically acceptable carrier. The Applicant’s specification defines a pharmaceutically composition where the active ingredient is present as a powder, granules, a solution, a suspension, an oil-in-water liquid emulsion, a water-in-oil liquid emulsion or even as a bolus, electuary or paste. The definition of polymorph is such that a polymorph is a specific crystalline form of a compound that can crystallize in different forms. However, a pharmaceutical composition of a polymorphic form of (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido[3,2- b][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide in a non-solid pharmaceutical composition no longer possesses its crystalline characteristics and therefore the x-ray diffraction patterns or infrared spectra. Furthermore, claims 21-34 are not limited to solids, but any pharmaceutical composition including solutions or process of preparing the pharmaceutical compositions. Polymorphs are distinguishable by various analytical techniques, especially X-ray powder diffraction patterns. With regards to the compositions the Carnegie Mellon Department of Physics teaches that the common industry practice when formulating a new drug to manufacture in dosage form is to rely on formulations (composition of inert additives) that worked with other drugs in the past. When this procedure fails (as is often the case) the formulation is changed by trial-and-error. The challenge is exacerbated by the fact that the formulation must achieve numerous, possibly competing objectives, such as control of chemical stability, disintegration and dissolution rates, polymorphism, crystal habit, and dosage uniformity. Because these systems have such complex compositions, and interactions between two or more formulation components often lead to unexpected consequences for one or more of the design objectives; there are few reliable, rational formulation design rules. Some formulations preserve the correct polymorph, others do not, and the reasons are usually not understood. This is a severe barrier in the pharmaceutical industry. Our aim is to develop new tools to give fundamental insight into identifying and controlling polymorphism in industrial processes through a molecular-level understanding. The applicants are not specifically claiming solid pharmaceutical compositions, but a composition comprising the compound (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido[3,2- b][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide. The following is a list of pharmaceutically acceptable excipients approved by the Food and Drug Administration anhydrous citric acid, cyclomethicone, dimethiconol/trimethylsiloxysilicate crosspolymer, dL-lactide and glycolide copolymer 12000 acid, ethylcellulose, flavor mixed fruit PFC-9970, Flavor raspberry 998, isopropyl alcohol, L-lactic acid, maltitol, medium chain tryglycerides, mineral oil, polysorbate 20, anhydrous sodium phosphate dibasic, dihydrate sodium phosphate dibasic and sodium stearyl fumarate where many result is a liquid, solution, etc. Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDA L COLEMAN whose telephone number is (571)272-0665. The examiner can normally be reached Mon-Fri 10-6 (flex). 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, Jeffrey H. Murray can be reached at 571-272-9023. 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. /BRENDA L COLEMAN/Primary Examiner, Art Unit 1624ab
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Prosecution Timeline

Apr 25, 2024
Application Filed
Jan 28, 2026
Non-Final Rejection — §102, §103 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
75%
Grant Probability
90%
With Interview (+15.4%)
2y 7m
Median Time to Grant
Low
PTA Risk
Based on 1604 resolved cases by this examiner. Grant probability derived from career allow rate.

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