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 communications entered 23JUN2026
Claims Cancelled 15-16
Claims Pending 1-14,17-23
Claims Under Consideration 1-14,17-23
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.
Withdrawn Objection(s) and/or Rejection(s)
All rejections from the previous action are hereby withdrawn in view of Applicant’s amendments.
New Claim Rejection(s) – 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.
Claims 1-4,6-14,17,18,20-23 are rejected under 35 U.S.C. 103 as being unpatentable over Molecular Dimensions CryoProX™ & CryoSol™ brochure (public availability date 31DEC2025 per cite no. 3 on 7MAR2023 IDS) in view of Hennesey et al (2009 Acta Crystallographica Section D vol D65 pp 1001-3 cite no. 5 on 7MAR2023 IDS)
As in claims 1,2,3,7,8,9,13,14,18,20,21,22 and 23, Molecular Dimensions discloses throughout the document and especially at pp 2-3 of the CryoSol™ (MD1-90) section and p 3 of the first CryoProtX™ section, methods for selecting a soaking solution suitable for a biological macromolecule (e.g. protein) wherein the solution contains an organic solvent (os) and a compatible solute (cs) including steps of: first preparing a non-aqueous soaking solution (e.g. SM2-6) by mixing organic solvents such as the alkylated sulfoxide DMSO and/or dioxane and compatible solutes such as polyols including ethylene glycol and/or glycerol and/or the polyhydric alcohol MPD; transferring at least one crystal of the biological macromolecular crystal into the solution prepared in the first step into a cryo-tray while controlling the crystal(s) such as to prevent over-dehydration; and selecting a non-aqueous soaking solution which is suitable for soaking the crystal (e.g. that dissolves a hydrophobic protein ligand such as a small molecule fragment or probe that diffuses into said crystal(s) specifically binding to the protein). Said DMSO or dioxane are aprotic solvents with low reactivity and can dissolve small molecules. Moreover, at p 2 of the first CryoProtX™ section, Molecular Dimensions suggests additives including sugars and PEG400 like claims 4 and 6.
Molecular Dimensions does not explicitly teach an array with multiple series of concentration gradients such as set forth in claims 10-12 and 17.
Hennesey et al disclose throughout the document and especially the first page, the four corners method toward designing crystal screens in N-dimensional grids. More particularly and like claims 10,11,12 and 17, in the abstract, section 2 and figures 1 and 2, Hennesey et al suggest a step gradient of key reagents, wherein, for instance when N is 3, trays for screening three reagent concentrations, each tray having rows (X) of increasing proportions of a first reagent (and decreasing concentrations of a second reagent); a similar gradients for a third and fourth reagent in the tray columns (Y); and additional trays for further reagents (Z, etc).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have used Hennesey’s four corners technique for refining the non-aqueous soaking solutions sparse-matrix approach of Molecular Dimensions.
One of ordinary skill in the art would have been motivated to have used Hennesey’s four corners technique for refining the non-aqueous soaking solutions sold by Molecular Dimensions with a reasonable expectation of success since the former is less tedious, more systematic than such sparse-matrix technique and, in fact, reduces pipetting errors, as noted by Hennessey in section 1.
New Claim Rejection(s) – 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 1-14,17-23 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-10,12,13,16-20,22,25,27 of copending Application No. 18/025107 in view of the Molecular Dimensions CryoProX™ & CryoSol™ brochure (public availability date 31DEC2025 per cite no. 3 on 7MAR2023 IDS)
Although the conflicting claims are not identical, they are not patently distinct from each other because, for example, said present claims represent obvious variants of the subject matter recited in the ‘107 claims or alternatively overlap in scope to a large extent and, as a result, the overlapping claims are similarly rendered obvious.
The following is illustrative.
For claim(s) 2,6 ‘107 claims the same cs polyol and PEG (e.g. see claim(s) 2,6)
For claim(s) 4, ‘107 claims the same sugars (e.g. see claim(s) 4).
For claim(s) 5,20 ‘107 claims the same methylamines and amino acids (e.g. see claim(s) 5,27).
For claim(s) 21,22,23 ‘107 claims the same organic solvents (e.g. see claim(s) 22.20,25).
In so far as the ‘107 claims do not explicitly recite the non-aqueous soaking solution recited in the present claims, as mentioned supra, Molecular Dimensions discloses crystal soaking solutions comprising ethylene glycol and/or glycerol and/or the polyhydric alcohol MPD in DMSO or dioxane (cf pp 2-3 of the CryoSol™ (MD1-90) section).
As such, it would have been prima facie obvious for one of ordinary skill in the art to have used Molecular Dimension’s soaking solutions with methods and equipment of ‘107 to arrive at the subject matter presently claimed.
One of ordinary skill in the art would have been motivated to have used Molecular Dimension’s soaking solutions with methods and equipment claimed in ‘107 and arrive at the subject matter presently claimed with a reasonable expectation of success in light of commercial availability thereof and for the benefit of dissolving hydrophobic ligands for co-crystallography.
Moreover, it would have been obvious to one having ordinary skill in the art at the time the invention was made to modify embodiments of ‘107 that fall outside the scope of the present application to select a specifically disclosed embodiment that falls within the scope of the present application because each set of claims concern solvents and cryoprotection additives with similar physiochemical properties for the same purpose of enhancing macromolecular co-crystal stability. Furthermore, one of ordinary skill in the art would have been motivated to make such a modification because such modifications are disclosed as “preferred” since the dependent claims of ‘107 “teach toward” Applicant’s presently claimed method.
In so far as the ‘107 methods include water it is noted the presently claimed method only requires a non-aqueous solution in the first step of independent claims 1 and 10, that is the claims are open to additional elements by using the preamble transition term “comprising” (see MPEP 2111.03 sections I-II)
This is a provisional obviousness-type double patenting rejection.
Claims 1-14,17-23 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-10,12,13,16-20,22,25,27 of copending Application No. 18/025100 in view of the Molecular Dimensions CryoProX™ & CryoSol™ brochure (public availability date 31DEC2025 per cite no. 3 on 7MAR2023 IDS)
Although the conflicting claims are not identical, they are not patently distinct from each other because, for example, said present claims represent obvious variants of the subject matter recited in the ‘100 claims or alternatively overlap in scope to a large extent and, as a result, the overlapping claims are similarly rendered obvious.
The following is illustrative.
For claim(s) 2,6 ‘100 claims the same polyol including PEG400 (e.g. see claim(s) 2,6)
For claim(s) 5,20 ‘100 claims the same methylamines and amino acids (e.g. see claim(s) 5,25).
For claim(s) 21,22,23 ‘100 claims the same organic solvents (e.g. see claim(s) 3,22,23).
In so far as the ‘100 claims do not explicitly recite the non-aqueous soaking solution recited in the present claims, Molecular Dimensions discloses crystal soaking solutions comprising ethylene glycol and/or glycerol and/or the polyhydric alcohol MPD in DMSO or dioxane (cf pp 2-3 of the CryoSol™ (MD1-90) section) as well as sugar additives.
It would have been prima facie obvious for one of ordinary skill in the art to have used Molecular Dimension’s soaking solutions with methods and equipment of ‘100 to arrive at the subject matter presently claimed.
One of ordinary skill in the art would have been motivated to have used Molecular Dimension’s soaking solutions with methods and equipment claimed in ‘100 and arrive at the subject matter presently claimed with a reasonable expectation of success in light of commercial availability thereof and for the benefit of dissolving hydrophobic ligands for co-crystallography.
Moreover, it would have been obvious to one having ordinary skill in the art at the time the invention was made to modify embodiments of ‘100 that fall outside the scope of the present application to select a specifically disclosed embodiment that falls within the scope of the present application because each set of claims concern solvents and cryoprotection additives with similar physiochemical properties for the same purpose of enhancing macromolecular co-crystal stability Furthermore, one of ordinary skill in the art would have been motivated to make such a modification because such modifications are disclosed as “preferred” since the dependent claims of ‘100 “teach toward” Applicant’s presently claimed method.
In so far as the ‘100 methods include water it is noted the presently claimed method only requires a non-aqueous solution in the first step of independent claims 1 and 10, that is the claims are open to additional elements by using the preamble transition term “comprising” (see MPEP 2111.03 sections I-II)
This is a provisional obviousness-type double patenting rejection.
New 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 1-14,17-23 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.
Claim 19 recites the limitation "x" in line 1. There is insufficient antecedent basis for this term in the claim, rendering the metes and bounds uncertain.
Claim 1 is 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. See MPEP § 2172.01. The omitted structural cooperative relationships which render the metes and bounds uncertain are as follows.
Claim 1 line 15 is drawn to a mixture of “such” solvents, whereas it is not clear which solvents such is referring to, in so far as polyols such as PEG400 is a solvent, polyhydric alcohols including ethylene glycol and glycerol are organic solvents and even methylamine is a solvent.
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 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.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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.
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/CHRISTOPHER M GROSS/
Primary Examiner, Art Unit 1684
