DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group II in the reply filed on September 24 2025 is acknowledged. Claims 1-5, 7, 11-14, 18-22, 25-26, 30 and 32-33 are pending in the application. Claims 1-5, 7, 11-14 and 18-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 24 2025. Accordingly, claims 25-26, 30 and 32-33 are being examined on the merits herein.
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
This application is a 371 of PCT/EP2021/0691 62 07/09/2021 which claims priority to EUROPEAN PATENT OFFICE (EPO) 21305795.3 (06/10/2021), EUROPEAN PATENT OFFICE (EPO) 20185871.9 (07/15/2020) and EUROPEAN PATENT OFFICE (EPO) 20306378.9 (11/13/2020) as reflected in the filing receipt issued on August 8 2024.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on June 29 2023 and September 24 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See for example paragraph 0002 and 00147 of the specification as originally filed.
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.
Claim 32 is 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 32 as currently written is vague and indefinite. The claim recites the viscosity is equivalent to a viscosity produced by glycerol at a concentration of 5 wt.% to 40 wt.% but fails to indicate the temperature at which the viscosity of the glycerol is measured. As evidenced by Glycerine Producers’ Association, the viscosity of glycerol (aka glycerin)/water solutions changes based on the temperature at which it is measured (see page 10, Table 17). Thus the metes and bounds of the claim are unclear.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
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.
Claims 25-26 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Omenetto et al. (WO2014085725) in view of Efcavitch et al. (USPGPUB No. 20140363852) as evidenced by Glycerine Producers’ Association (1963).
Applicant Claims
The instant application claims a printable template-free polymerase ink, comprising: an aqueous solution comprising a template-free polymerase having a concentration of 1.0 µM to 30 µM; wherein whenever the ink is printed to a substrate, printed droplets each have a volume of 0.1 pL to 5 nL of the aqueous solution and wherein the ink is characterized by a viscosity of about 1 centipoise to about 20 centipoise when viscosity is measured at room temperature; and a surface tension of about 15 dynes/cm to about 50 dynes/cm when measured at room temperature.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Omenetto et al. is directed to biopolymer-based inks and use thereof. Claimed is an aqueous unit composition comprising a structural protein present at a concentration of between about 0.1-10 (wt/vol)% wherein the liquid unit composition is a liquid droplet having a viscosity of between about 1-20 centipoise at room temperature and a volume between 0.1-100 pL (claim 1). The composition has a surface tension of between about 15-50 dynes/cm at room temperature (claim 4). Proteins include enzymes (page 9, lines 7). The formulations typically contain at least one viscosity-modifying agent, i.e. viscosity modifiers or adjusters. The optimal range of viscosity is important for ensuring high quality, reproducible inkjet printing (page 17). Additives such as enzymes can be added (pages 20-21). Proteins formulated as bio-inks are inkjet-printed in aqueous solutions. The composition of the solution influences its surface tension. For high values of surface tension, the applied force that stretches and eventually causes the ejection of the drop is lower than the cohesive counter-force. Indeed, the droplet resists to the external force, resulting in lack of injection (page 8). Proteins are by nature macromolecules and consequently the viscosity of their solutions is often dramatically affected by changes in concentration. At higher concentrations, the capillary force is insufficient to break the filament of the droplet during the ejection and the droplet retracts back into the nozzle (page 8).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Omenetto et al. teach printable inks with the same viscosity and surface tension, Omenetto et al. does not expressly teach a template-free polymerase. However, this deficiency is cured by Efcavitch et al.
Efcavitch et al. is directed to methods and apparatus for synthesizing nucleic acids. Taught is a nucleotidyl transferase, e.g. a terminal deoxynucleotidyl transferase (TdT) or any other enzyme which elongates DNA or RNA strands without template direction (paragraph 0006). Reagents such as TdT may be deposited into a reaction chamber using inkjet printing technology or piezoelectric drop-on-demand (DOD) inkjet. Inkjet printing can be used to form droplets which can be deposed into a reaction chamber (paragraph 0074). Taught is using inkjet printing technology which includes an appropriate amount of TdT or any other enzyme which elongates DNA or RNA strand without template direction (paragraph 0071).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Omenetto et al. and Efcavitch et al. and utilize TdT in the bioink of Omenetto et al. One skilled in the art would have been motivated to utilize TdT as it is a particular protein (aka enzyme) which can be used in inkjet printing as taught by Efcavitch et al. Therefore, one skilled in the art would have been motivated to utilize an aqueous ink composition in order to deliver the polymerase.
Regarding the claimed concentration, viscosity and surface tension, Omenetto et al. teaches the same viscosity and surface tension. Omenetto et al. teaches protein in concentrations of .1-10 (wt/vol)%. Efcavitch et al. teaches using the TdT in an appropriate amount. Since the viscosity and surface tension are important factors as taught by Omenetto et al., one skilled in the art would have been motivated to manipulate the amount of TdT in order to ensure it is an appropriate amount but also not negatively affecting the viscosity and surface tension which are important factors for delivery from an inkjet as taught by Omenetto et al.
Regarding claim 26, Omenetto et al. expressly teaches the inclusion of a viscosity-modifying agent.
Regarding claim 32, as set forth above Omenetto et al. teaches a viscosity of 1 to 20 centipoise. As evidenced by Glycerine Producers’ Association the viscosity of glycerol (at 20-30 ³C) from 10-40 wt% has a viscosity in centipoises from 1.03-3.72. Therefore, viscosity taught in Omenetto et al. overlaps this range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Claims 25-26, 30 and 32 rejected under 35 U.S.C. 103 as being unpatentable over Omenetto et al. in view of Efcavitch et al. as evidenced by Glycerine Producers’ Association as applied to claims 25-26 and 32 above and in further view of Cong (US Patent No. 8889232) as evidenced by Su et al. (USPGPUB No. 20180171064).
Applicant Claims
The instant application claims the printable template-free polymerase ink for catalyzing a reaction between a 3'-O-amino-nucleoside triphosphate and a free 3'-hydroxyl of an initiator or an elongated fragment thereof, the printable template-free polymerase ink further comprising an aldehyde scavenger.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Omenetto et al. and Efcavitch et al. are set forth above. Omenetto et al. teaches additives can be added to the ink.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
The inclusion of a aldehyde scavenger is not taught. However, this deficiency is cured by Cong as evidenced by Su et al.
Cong is directed to a radiation curable ink. The ink is for ink-jet printing (column 1, lines 65-66). Additives can be included. These include stabilizers. Stabilizers are used to improve the shelf-life and photolytic stability of ink compositions as well as improve the stability of the ink against heat. Free radical scavengers include 4-methoxyphenol (column 5, lines 39-60).
As evidenced by Su et al. 4-methoxyphenol is an aldehyde scavenger (paragraph 0043; claim 3).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Omenetto et al., Efcavitch et al. and Cong and utilize 4-methoxyphenol in the ink composition. One skilled in the art would have been motivated to add 4-methoxyphenol in order to improve the shelf-life as well as the stability of the ink against heat as taught by Cong. Since Omenetto et al. suggests additives can be included and Cong teaches the addition of a stabilizer to an ink for inkjet printing there is a reasonable expectation of success.
Regarding the claimed for catalyzing a reaction between a 3'-O-amino-nucleoside triphosphate and a free 3'-hydroxyl of an initiator or an elongated fragment thereof, this is an intended use. A recitation of the intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Note: MPEP 2111.02 and MPEP 2145. Here the prior art teaches the same polymerase and therefore would clearly be capable of the intended use.
Claims 25-26 and 32 -33 are rejected under 35 U.S.C. 103 as being unpatentable over Omenetto et al. in view of Efcavitch et al. as evidenced by Glycerine Producers’ Association as applied to claims 25-26 and 32 above and in further view of Champion et al. (USPGPUB No. 20190211315, cited on PTO Form 1449).
Applicant Claims
The instant application claims said template-free polymerase is a terminal deoxynucleotidyltransferase (TdT) variant.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Omenetto et al. and Efcavitch et al. are set forth above.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
TdT variants are not expressly taught. However, this deficiency is cured by Champion et al.
Champion et al. is directed to variants of terminal deoxynucleotidyl transferase and uses thereof. Claimed are variants of TdT which are capable of synthesizing a nucleic acid fragment without template (claim 17). Taught are variants, specifically modifying amino acids, to improve the ability of the TdT for synthesizing polynucleotides (paragraph 0008).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Omenetto et al., Efcavitch et al. and Champion et al. and utilize a TdT variant. One skilled in the art would have been motivated to use the variants of Champion et al. as they are specifically taught as improving the ability for synthesizing polynucleotides. There is a reasonable expectation of success as Efcavitch et al. teaches the use of TdT with inkjet printing.
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 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 25-26 and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-20 of copending Application No. 19143773 in view of Omenetto et al. as evidenced by Glycerine Producers’ Association.
Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant application claims a printable template-free polymerase ink, comprising: an aqueous solution comprising a template-free polymerase having a concentration of 1.0 µM to 30 µM; wherein whenever the ink is printed to a substrate, printed droplets each have a volume of 0.1 pL to 5 nL of the aqueous solution and wherein the ink is characterized by a viscosity of about 1 centipoise to about 20 centipoise when viscosity is measured at room temperature; and a surface tension of about 15 dynes/cm to about 50 dynes/cm when measured at room temperature.
Copending ‘773 claims a template-free polymerase ink for inkjet printings comprising: an aqueous solution comprising a template-free polymerase having a concentration of in a range of from 1.0 µM to 30 µM; wherein whenever the ink is printed as droplets to a substrate, printed droplets each have a volume in the range of 0.1 pL to 5 nL of the aqueous solution and wherein the ink comprises a variable viscosity modifier having a first viscosity in the range of from 2-20 mPa.s (which is the same as centipoise) whenever the temperature is in the range of from 5-30°C and a second viscosity in the range of from 2 to 3 mPa.s whenever the temperature is in the range of from 35-60°C;wherein the first viscosity and the second viscosity are not the same.
While copending ‘773 claims the same template-free polymerase with an overlapping viscosity and the same concentration, copending ‘773 does not claim the surface tension. However, this deficiency is cured by Omenetto et al.
Omenetto et al. is directed to biopolymer-based inks and use thereof. The composition has a surface tension of between about 15-50 dynes/cm at room temperature (claim 4). Proteins formulated as bio-inks are inkjet-printed in aqueous solutions. The composition of the solution influences its surface tension. For high values of surface tension, the applied force that stretches and eventually causes the ejection of the drop is lower than the cohesive counter-force. Indeed, the droplet resists to the external force, resulting in lack of injection (page 8).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘773 and Omenetto et al. and utilize a surface tension of 15-50 dynes/cm. One skilled in the art would have been motivated to utilize this surface tension as this is a surface tension known to be useful for ink which are used in inkjet printing as taught by Omenetto et al.
Regarding claim 26, copending ‘773 expressly claims the inclusion of a viscosity-modifying agent.
Regarding claim 32, as set forth above Copending ‘773 teaches a viscosity of 2-20 mPa.s (which is the same as centipoise) whenever the temperature is in the range of from 5-30°C. As evidenced by Glycerine Producers’ Association the viscosity of glycerol (at 20-30 ³C) from 10-40 wt% has a viscosity in centipoises from 1.03-3.72. Therefore, viscosity taught in copending ‘773 overlaps this range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Claims 25-26, 30 and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-20 of copending Application No. 19143773 in view of Omenetto et al. as evidenced by Glycerine Producers’ Association as applied to claims 25-26 and 32 as set forth above in further view of Cong as evidenced by Su et al.
Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims the printable template-free polymerase ink for catalyzing a reaction between a 3'-O-amino-nucleoside triphosphate and a free 3'-hydroxyl of an initiator or an elongated fragment thereof, the printable template-free polymerase ink further comprising an aldehyde scavenger.
The teachings of copending ‘773 and Omenetto et al. are set forth above. Omenetto et al. teaches additives can be added to the ink.
Copending ‘773 does not claim the inclusion of a aldehyde scavenger. However, this deficiency is cured by Cong as evidenced by Su et al.
Cong is directed to a radiation curable ink. The ink is for ink-jet printing (column 1, lines 65-66). Additives can be included. These include stabilizers. Stabilizers are used to improve the shelf-life and photolytic stability of ink compositions as well as improve the stability of the ink against heat. Free radical scavengers include 4-methoxyphenol (column 5, lines 39-60).
As evidenced by Su et al. 4-methoxyphenol is an aldehyde scavenger (paragraph 0043; claim 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Copending ‘773, Omenetto et al., and Cong and utilize 4-methoxyphenol in the ink composition. One skilled in the art would have been motivated to add 4-methoxyphenol in order to improve the shelf-life as well as the stability of the ink against heat as taught by Cong. Since Omenetto et al. suggests additives can be included and Cong teaches the addition of a stabilizer to an ink for inkjet printing there is a reasonable expectation of success.
Regarding the claimed for catalyzing a reaction between a 3'-O-amino-nucleoside triphosphate and a free 3'-hydroxyl of an initiator or an elongated fragment thereof, this is an intended use. A recitation of the intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Note: MPEP 2111.02 and MPEP 2145. Here the prior art copending ‘773 teaches the same polymerase and therefore would clearly be capable of the intended use.
Claims 25-26 and 32-33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-20 of copending Application No. 19143773 in view of Omenetto et al. as evidenced by Glycerine Producers’ Association as applied to claims 25-26 and 32 above and in further view of Champion et al.
Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims said template-free polymerase is a terminal deoxynucleotidyltransferase (TdT) variant.
The teachings of copending ‘773 and Omenetto et al. are set forth above.
TdT variants are not expressly claimed. However, this deficiency is cured by Champion et al.
Champion et al. is directed to variants of terminal deoxynucleotidyl transferase and uses thereof. Claimed are variants of TdT which are capable of synthesizing a nucleic acid fragment without template (claim 17). Taught are variants, specifically modifying amino acids, to improve the ability of the TdT for synthesizing polynucleotides (paragraph 0008).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘773, Omenetto et al., and Champion et al. and utilize a TdT variant. One skilled in the art would have been motivated to utilize the variants of Champion et al. as they are specifically taught as improving the ability for synthesizing polynucleotides. Since copending ‘773 claims a template-free polymerase and TdT is a template-free polymerase (aka without template), there is a reasonable expectation of success.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ABIGAIL VANHORN whose telephone number is (571)270-3502. The examiner can normally be reached M-Th 6 am-4 pm EST.
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/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636