Prosecution Insights
Last updated: April 19, 2026
Application No. 18/025,103

ARRAY, SOAKING SOLUTIONS AND METHOD OF SELECTING SOAKING CONDITIONS FOR SMALL MOLECULES IN BIOLOGICAL MACROMOLECULAR CRYSTALS

Non-Final OA §102§112§DP
Filed
Mar 07, 2023
Examiner
GROSS, CHRISTOPHER M
Art Unit
1684
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Crystalsfirst GmbH
OA Round
1 (Non-Final)
63%
Grant Probability
Moderate
1-2
OA Rounds
4y 1m
To Grant
99%
With Interview

Examiner Intelligence

Grants 63% of resolved cases
63%
Career Allow Rate
410 granted / 651 resolved
+3.0% vs TC avg
Strong +41% interview lift
Without
With
+41.2%
Interview Lift
resolved cases with interview
Typical timeline
4y 1m
Avg Prosecution
37 currently pending
Career history
688
Total Applications
across all art units

Statute-Specific Performance

§101
3.2%
-36.8% vs TC avg
§103
31.9%
-8.1% vs TC avg
§102
27.6%
-12.4% vs TC avg
§112
23.1%
-16.9% vs TC avg
Black line = Tech Center average estimate • Based on career data from 651 resolved cases

Office Action

§102 §112 §DP
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 . DETAILED ACTION Responsive to claim set of 7MAR2023 Claims pending 1-18 Claims currently under consideration 1-18 Priority This application has a filing date of 03/07/2023 and is a 371 of PCT/EP2021/074734 09/08/2021. Acknowledgment is made of applicant's claim for foreign priority based on an application EP 20195132.4 filed in Europe on 09/08/2020. It is noted, however, that applicant has not filed a certified copy of the EP 20195132.4 application as required by 37 CFR 1.55. 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. Claims 1-4,6-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by the Molecular Dimensions CryoProX™ & CryoSol™ brochure (public availability date 31DEC2025 per cite no. 3 on 7MAR2023 IDS). Molecular Dimensions discloses throughout, especially pp 2-4 of the first CryoProX™ section and p 4 of the second CryoProX™ section and figure 3, a method including steps of: 1) preparing a soaking solution by mixing and organic solvent (os) and compatible solute (cs); 2) transferring at least one crystal of a biological macromolecular crystal into the solution prepared in step 1); 3) controlling the crystal such as from evaporation; 4) selecting the soaking solution which is suitable for soaking the crystal by screening for ligand solubility, such that: the cs is, for example, a polyol such as PEG-400, ethylene glycol, glycerol or 2-methyl-2,4-pentanediol (MPD); and the os is, for instance, DMSO, an aprotic solvent of low reactivity, optionally including small molecule fragments such as low affinity inhibitors or drugs that inherently diffuse into the biological macromolecular crystal. The foregoing appears to read on: claims 1,2,3,4,6,7,8,9,13,14 & 15; and claims 10,11 & 12 when n=0. See also indefiniteness rejection below. Claims 17-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by the Teplitsky et al (2015 J. Structural Biology 191:49-58 - cite no. 9 on 7MAR2023 IDS) Teplisky et al teach throughout the document and especially the abstract and last paragraph at p 50 and figures 1 and 2 including legend, a 96 well MiTeGen in situ-1 crystallization plate™ array that comprises a first dimension of at least 12 individual non-aqueous soaking solutions and a second dimension of at least 8 individual non-aqueous soaking solutions wherein each of said soaking solutions is located in a separated compartment of said array, and wherein each of said soaking solution comprises DMSO and a compatible solute. Said array is fully capable of performing the method set forth in claim 1 and the soaking solution may be obtained therefrom the array by means such as acoustic droplet ejection if so desired. The foregoing reads on claims 17 and 18 when, for instance, n=m=1; x=12; and y=8. 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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b). Claims 1-14 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-10,12,13,17 of copending Application No. 18/025107 Although the claims at issue are not identical, they are not patentably distinct from each other because the steps set forth in said present claims comprising mixing an organic solvent and compatible solute to provide soaking solution(s), followed by transferring a biological macromolecule crystal thereto, then controlling the crystal and finally selecting a suitable soaking solution(s), wherein: the organic solvent may be DMSO or an aprotic liquid carbohydrate; and the compatible solute may be a polyol like PEG-400, ethylene glycol, glycerol or 2-methyl-2,4-pentanediol (MPD) or else a methylamine represent a genus of the same steps plus a crystallization solution and/or water (species) set forth in such conflicting claims of ‘107. This is a provisional obviousness-type double patenting rejection. 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 1-18 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 pre-AIA the applicant regards as the invention. Claims 1 and 10 each recite the limitation " the composition of a nonaqueous soaking solution" each in line 1. Claims 1 and 10 each recite the limitation " the crystal form of a biological macromolecule" each in line 2. There is insufficient antecedent basis for these limitation in the claim, rendering the metes and bounds uncertain. Claims 1,10,11,12,16 and 17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections or alternatively, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted structural cooperative relationships or omitted steps which render the metes and bounds uncertain are as follows. The final wherein clause of claim 1 drawn to “wherein the organic solvent is selected from ... protic or aprotic, of low reactivity, that can serve to solve small molecules...” is grammatically incongruent. In particular, it is not clear if the quoted organic solvent has a property of being protic or aprotic, has what of low reactivity nor has what that can solvate small molecules” Claim 16 is drawn to “for a method of small molecule screening for a biological macromolecular crystal, comprising performing the screening in a soaking solution according to claim 15.” which is a lone preposition, that lacks a noun and verb. Claims 10,11,12 and 17 each recite the term n, however no range is indicated. Claims 10 and 17 recite the term y, however no range is indicated. Consequently, it is ambiguous what claims 1,10,11,12,16,17 are intending to encompass. Each of claims 2-5, each recite phrase "more preferably” and “most preferably” that both render the claims indefinite because it is unclear whether the limitations following the phrase/term constitute the metes and bounds of the claim or not are part of the claimed invention. See MPEP § 2173.05(d). Moreover, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation of any (protic or aprotic) solvent, and the claim also recites liquid carbohydrates which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. In accordance with MPEP 2173.02: If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112, second paragraph, would be appropriate. See Morton Int ’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470, 28 USPQ2d 1190, 1195 (Fed. Cir. 1993). In so far as the metes and bounds of the offending claim(s) may not be interpreted properly for the reasons above, all dependent claims therefrom claim 1 and 10 are rejected as being indefinite as well. 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 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. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTOPHER M GROSS whose telephone number is (571)272-4446. The examiner can normally be reached M-F 10-6. 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, Heather Calamita can be reached on (571)272-2876. 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. /CHRISTOPHER M GROSS/Primary Examiner, Art Unit 1684
Read full office action

Prosecution Timeline

Mar 07, 2023
Application Filed
Jan 06, 2026
Non-Final Rejection — §102, §112, §DP (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
63%
Grant Probability
99%
With Interview (+41.2%)
4y 1m
Median Time to Grant
Low
PTA Risk
Based on 651 resolved cases by this examiner. Grant probability derived from career allow rate.

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