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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 3/31/2026 and 7/29/2026 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Response to Amendment
Applicant’s remarks and amendments filed 6/2/2026, in response to the non-final rejection mailed 3/4/2026, are acknowledged and have been fully considered. Applicant’s amendment to the claims is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Any previous rejection or objection not mentioned herein have been withdrawn based upon Applicant’s amendments to the claims.
Claims 21 and 24-38 are pending and have been examined on the merits.
Claim Rejections - 35 USC § 103
Modified as necessitated by Applicant’s amendments
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 factual inquiries 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 21, 24, 27-30, and 32-38 are rejected under 35 U.S.C. 103 as being unpatentable over Beier et al. (US PGPub 20190256831, published 8/22/2019).
Beier et al. (US 20190256831) teaches a variant of a DNase parent, derived from Bacillus Cibi, wherein the variant has at least 80% sequence identity to the polypeptide shown in SEQ ID NO: 1 and the variant has DNase activity, wherein the variant comprises one or both motifs [D/M/L][S/T]GYSR[D/N] (SEQ ID NO: 25) or ASXNRSKG (SEQ ID NO: 26) (as also disclosed in page 21, lines 23-33 of the instant application), wherein the variant comprises one or more substitutions compared to SEQ ID NO: 1, and wherein the substitutions comprise, inter alia, T65I, N61D, S82R, K107Q, and/or T127S (claim 1, Abstract, and [0092]-[0094]; [0100]).
Beier teaches that “Each of these mutations provides at least one improved property, such as improved stability, when introduced in SEQ ID NO: 1 or polypeptides having at least 60% sequence identity hereto. It will be clear to the skilled artisan that each of these mutations provides an improved effect thus 2, 3, 4 etc. of the above substitutions may increase this effect. Thus some aspects of the invention relate to DNase variants comprising at least two, three, four, five, six, seven, eight of the substitutions” ([0125]). The substitutions to be selected from comprise N61D, T65I, T65V, S82R, K107Q, T127S and T127V ([0125], claim 12), as recited in the instant claims. In Table 1 (see pages 42-45 therein), Beier teaches that these mutations impart improvements to the stability, indicated by a “half-life improvement factor”. Of note, Beier teaches that T65I = a HIF of 1.14; N61D = 1.09; S82R= 1.10; K107Q = 1.14; and T127S = 1.20.
SEQ ID NO:1 of Beier is about 87.4 percent identical to the variant SEQ ID NO:1 of the instant invention. It is noted that SEQ ID NO:27 of the instant application, reciting the parent DNase, from Bacillus cibi, is identical to SEQ ID NO:1 of Beier. The aligned sequences are of the same length and the substitutions made thereto are of the same comparative positions as in the instant invention.
Further, regarding the additional substitutions recited in dependent claims 27-29, Beier teaches the substitutions may include, inter alia, Q14R, the variant S25P (note that the instant claim requires a serine at position 25 in “P25S”, Beier teaches a sequence that has serine and may be mutated to proline), D56I, D56L, S68L, T77Y (e.g. Y77), Q109R (e.g. Q109), S116D (e.g. S116), and S181W (thus a variant with W181) ([0125]).
Regarding claim 30, it is noted that many of the possible specified residues pertain to the original sequence of the instant SEQ ID NO:1, in other words the limitations are reciting that these positions are the original and are not mutated. Beier teaches at least the following mutations, made to the original parental sequence (the same as SEQ ID NO:27 herein): T1I, S13Y, T22P, S25P, S27L, S39P, S42G, S57W, S59V, V76L, T77Y, Q109R, S116D, S144P, A147H, S167L, G175D ([0125]), thus teaching at least 5 (Beier teaches “variants comprising at least two, three, four, five, six, seven, eight of the substitutions”, [0125]).
Therefore, prior to the effective filing date of the instant invention, to one of ordinary skill in the art, the instantly claimed DNase variant would have been prima facie obvious over the teachings of Beier, which teaches a variant having 87.4 identity to the claimed SEQ ID NO:1 and having at least two, three, four, five, six, seven, eight of the substitutions taught therein, including T65I, N61D, S82R, K107Q, and/or T127S as the instant claim 21.
One would have been motivated by Beier to produce a DNase variant from the same starting parental DNase as the instantly claimed mutant by combining the substitutions taught therein. The substitutions taught in Beier are beneficial because of the improved stability on the DNase polypeptide. These substitutions would predictably convey the same properties to the instantly claimed sequence. Thus, one having ordinary skill in the art would have arrived at the instantly claimed variant, of Claim 21, having either at least the T65I substitution and two of the other recited mutations. Further, Beier suggests explicitly that it is clear to the skilled artisan that because each of these mutations provides an improved effect thus 2, 3, 4 etc. of the above substitutions may increase the effect.
MPEP§ 2143.I.(E) describes that in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007), one of the exemplary rationales which support a conclusion of obviousness is "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success: “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103."KSR, 550 U.S. at 421, 82 USPQ2d at 1397.”. In the instant case, the specific substitutions N61D, T65I, T65V, S82R, K107Q, T127S, and T127V as recited in claim 21 are taught in Beier to each provide improved stability to the same DNase parental polypeptide. Additional mutations, such as Q14R, D56I, D56L, and S68L, recited in the dependent claims, are also explicitly taught in Beier to provide improve stability.
Thus, variants of the DNase having these substitutions as claimed, which singularly provide stability as taught in Beier, are known to the art. It would have been a matter of routine optimization comprising selecting and combining these mutations, and testing the resulting mutants, to arrive at one or more of the instantly claimed combinations.
Regarding claim 24, the starting sequence of the DNase in Beier is 87.4% identical to that of the instantly claimed SEQ ID NO:1 (Appendix A below). With the substitutions applied, changing 3-8 positions, the variant remains within 87% identity to the instantly recited variant.
Regarding claim 27, because one or more of these specific mutations are taught in Beier, and taught to provide improved stability, inclusion of one or more of these, including for example one or more of Q14R, D56I, D56L, and S68L, would have been obvious for the same reasons described above.
In regards to claims 28 and 29, the combinations taught in Beier would have led one of ordinary skill to produce at least a variant with one of these combinations of mutations: Q14R+N61D+T65I+S82R+K107Q; Q14R+T65I+K107Q+T127S; N61D+T65I+S82R+T127S; or N61D+T65I+S82R+K107Q (as in claim 29).
In regards to claim 30, Beier teaches mutations made to the original parental sequence (SEQ ID NO:27 herein) that include T1I, S13Y, T22P, S25P, S27L, S39P, S42G, S57W, S59V, V76L, T77Y, Q109R, S116D, S144P, A147H, S167L, G175D ([0125]), thus teaching at least 5 of these positions may be present. Combining these mutations with those taught elsewhere would have been logical continuations of the suggestions in Beier.
Regarding claim 32, these are mutations which revert the sequence of the instant SEQ ID NO:1 to that of SEQ ID NO:1 in Beier, which teaches a DNase with one or more of these positions (i.e. a T in position 1, a S in position 13 and so on). Regardless of how the mutation or residue is specified, the resulting polypeptide of the instant invention would be indistinguishable from one having the original residue (i.e. that of SEQ ID NO:1 in Beier). See pg 9, line 19 - pg 10, line 3 of the instant disclosure regarding naming conventions for these substitutions.
Regarding claims 33-38, the recited mutations N61D, T65I, S82R, K107Q, and T127S are taught in Beier. It is noted that a variant having all five of these mutations (e.g. N61D, T65I, S82R, K107Q, and T127S) would read on each of claims 33-38, as these are “comprising”-type claims. Thus, it is evident, for the reasons discussed above, that the combinations of substitution in the variants of claims 33-38 would have been prima facie obvious over the teachings of Beier, as described for claim 21 above.
From the teachings of Beier, it is apparent that there would have been a reasonable expectation of success in making the claimed polypeptide variants because the claimed parent DNase sequence is known to the art, the substitutions are taught to provide improved stability, and combinations of these are explicitly suggested in the reference.
Therefore, the invention of claims 21, 24, 27-30, and 32-38, as a whole, would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date, as evidenced by the cited references, especially in the absence of evidence to the contrary.
Claims 21 and 24-38 are rejected under 35 U.S.C. 103 as being unpatentable over Beier et al. (US PGPub 20190256831) as applied to claim 21, 24, 27-30, and 32-38 above, and further in view of Oestergaard et al. (US PGPub 20190127664, published 5/2/2019), to include the rejections of claims 25-26 and 31.
Beier et al. makes obvious the DNase variant of claim 21 as described above.
Beier teaches a DNase variant having 87.4 identity to the claimed SEQ ID NO:1 and having at least two, three, four, five, six, seven, eight of the substitutions taught therein, including T65I or T65V, N61D, S82R, K107Q, and/or T127V ([0125]).
However, Beier does not teach a DNase variant having at least 90 or 95% sequence identity to SEQ ID NO:1 and the recited mutations (as in claims 25 and 26), nor does it teach a variant comprising 15-18 of the indicated residues in claim 31.
Oestergaard (US 20190127664) pertains to detergent compositions comprising polypeptide variants and teaches DNase variants exhibiting alterations relative to the parent DNase in one or more properties including: wash performance, detergent stability and/or storage stability (Abstract, [0002]). Oestergaard teaches sets of mutations that comprise, inter alia, T65V, T127V, N61D, and/or S82R (see [0169], [0174] and claims 1, 6, and 11). SEQ ID NO:28, comprising a DNase variant taught in Oestergaard et al. that is 96.5% identical to the instantly recited variant sequence of SEQ ID NO:1, according to the alignment of the two sequences accompanying this action (see Appendix B below). Oestergaard also teaches additional mutations, such as Q14R ([0170]), L33K ([0172]), Q48D ([0172]), D56I and D56L ([0172]), S66Y ([0172]), S68L ([0170]), as recited in the instant claim 27.
Regarding claims 30-32, the mutations taught in Oestergaard also include T1I, S13Y, T22P, S25P, S27L, S39P, S42G, S57W, S59V, V76L, T77Y, Q109R, S116D, T127L, S144P, A147H, S167L and G175D among others ([0169]-[0172])). When examining the sequence of SEQ ID NO:28 in Oestergaard, it is noted that the following are present: I at position 1, Y at position 13, P at position 22, L at position 27, G at position 42, W at position 57, V at position 59, L at position 76, Y at position 77, R at position 109, D at position 116, P at position 144, H at position 147, L at position 167, D at position 175. Further, according to the substitutions taught therein, the variant of Oestergaard can also include P in position 25, P in position 39, and L at position 181 (see [0169], at least).
Oestergaard teaches producing a mutant protease according to SEQ ID NO:28 therein (analogous to SEQ ID NO:1 of the instant disclosure) and those having additional substitutions, then testing these substituted combinations for stability under stressed conditions and in the presence of various detergents and proteases (see e.g. Tables 2, 3, and 6). Oestergaard teaches that combinations of mutations, from among those discussed above results in variants with DNase activity and improved half-life stability. As one specific example, Oestergaard teaches a sequence having T1I, S13Y, T22P, S25P, S27L, L33K, S39P, S42G, D56L, S57W, S59V, T65V, S66Y, V76L, T77Y, Q109R, S116D, T127V, S144P, A147H, G162E, S167L, and G175D, which by lack of any specific mutation also includes an S at position 181 (e.g. akin to providing the L181S variant of the instant claims - see the last row of Tables 2, 3, and 4 and compare to SEQ ID NO:1 and 28 of Oestergaard), which has higher residual activity after the stress treatments (i.e. RAR after protease, sulfite, and detergent assay).
Thus, before the effective filing date of the claimed invention, it would have been prima facie obvious in view of the combined teachings of Beier and Oestergaard to produce a variant having at least three of the mutations as taught in Beier et al. above and maintains at least 95% sequence identity to the sequence of SEQ ID NO:1 in the instant application - as in claims 25 and 26 - and also has 15-18 of the residue mutations as recited in claims 31.
One would have been motivated by the teachings of Oestergaard, which teaches that DNase variants comprising substitutions of SEQ ID NO:28, comprising multiple mutations compared to SEQ ID NO:1 of Oestergaard (the parental DNase of B. cibi, the same as taught in Beier), and comprising ~97% sequence identity to SEQ ID NO:1 of the instant application, have increase stability and are resistant to protease, sulfite, and detergent exposure. There would have been a predictable benefit of obtaining a DNase with increased stability as taught in both Beier and Oestergaard when producing a DNase variant having T65I (as explicitly disclosed in Beier) and at least two other mutations, especially one of T127S, N61D, and/or S82R because these are among the finite number of mutations taught in the prior art that increase the enzyme’s stability.
When producing a mutant protein variant, according to all of the teachings and motivation provided by Beier, selecting from among those mutations known in the art would have been a matter of judicious selection and routine optimization to one having ordinary skill in the art. Further, means for testing, assaying, and determining the suitability of such mutations are clearly taught in Oestergaard.
From the teachings of Oestergaard and Beier, it is apparent that there would have been a reasonable expectation of success in making the claimed DNase variants because the claimed DNase sequences are known to the art, the individual substitutions are taught to provide improved stability, and the benefits of combining such substitutions are taught in the references.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date, as evidenced by the cited references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments regarding the rejections of the claims under 35 U.S.C. § 103, on pages 12-13 of the remarks filed 6/2/2026 have been fully considered but they are not persuasive.
Applicant argues that “Beier et al. do not teach or suggest DNase variants comprising a specific combination of substitutions. In particular, Beier et al. do not teach or suggest DNase variants comprising T651 and at least two substitutions selected from the group consisting of N61D, S82R, K107Q, and T127S. Moreover, the Examples of the present application demonstrate that the claimed variants have a substantially improved stability (measured as half-life improvement factor) compared to the DNase of SEQ ID NO: 1. See, e.g., the results in Table 2 which show a significant improvement in concentrated liquid detergent (Tide Pods® 3-in-1). These results are not suggested by Beier et al. and therefore are surprising and unexpected.”
Further, Applicant argues that “Oestergaard et al. also do not teach or suggest DNase variants comprising T651 and at least two substitutions selected from the group consisting of N61D, S82R, K107Q, and T127S. Moreover, the Examples of the present application demonstrate that the claimed variants have a substantially improved stability (measured as half-life improvement factor) compared to the DNase of SEQ ID NO: 1. See, e.g., the results in Table 2 show a significant improvement in concentrated liquid detergent (Tide Pods® 3-in-1). These results are not suggested by Beier et al. or Oestergaard et al. and therefore are surprising and unexpected.” These arguments have been fully considered but are not persuasive.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the improved stability, measured as half-life improvement factor) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Further, compositions comprising enzymes having the same sequence and same mutations will predictably have the same properties, as the structure of the enzyme determined the functional properties. Thus, because the instant claims are drawn to compositions, the teachings of Beier and/or Oestergaard are deemed to teach all of the required structure.
It is important to note that the instant claims are comprising-type claims and thus are not limited to only the specific mutations as Applicant appears to argue. The claims also recite “at least two substitutions” but this does not exclude additional mutations.
As set forth above, Beier et al. teaches that “Each of these mutations provides at least one improved property, such as improved stability, when introduced in SEQ ID NO: 1 or polypeptides having at least 60% sequence identity hereto. It will be clear to the skilled artisan that each of these mutations provides an improved effect thus 2, 3, 4 etc. of the above substitutions may increase this effect. Thus some aspects of the invention relate to DNase variants comprising at least two, three, four, five, six, seven, eight of the substitutions” ([0125]).
It is without question that the list of possible substitutions taught in the cited art includes N61D, T65I, S82R, K107Q, and T127S, as recited in the instant claims. Beier demonstrates, in Table 1 (see pages 42-45), that these mutations impart improvements to the stability, indicated by a “half-life improvement factor”. Beier teaches that T65I = a HIF of 1.14; N61D = 1.09; S82R= 1.10; K107Q = 1.14; and T127S = 1.20. Thus, the cited art provides teachings of each of the possible substitutions, and provides objective evidence that each has some contribution to increased stability. Further, Beier also teaches that one of ordinary skill would be motivated to make combinations of 2, 3, 4, et cetera, of the mutations, with the predictable result of improving the effect (see the section of [0125] cited above).
MPEP 2141.II.C establishes that "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton."KSR, 550 U.S. at 421, 82 USPQ2d at 1397. "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle."Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ."Id. at 418, 82 USPQ2d at 1396.
MPEP§ 2143.I.(E), cited previously, describes that in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007), one of the exemplary rationales which support a conclusion of obviousness is "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success: “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103."KSR, 550 U.S. at 421, 82 USPQ2d at 1397.”. In the instant case, the specific substitutions N61D, T65I, S82R, K107Q, and T127S, as recited in amended claim 21 are each taught in Beier to each provide improved stability to the same DNase parental polypeptide, having substantial sequence identity to that which is instantly claimed. It would have been a matter of routine optimization comprising selecting and combining these mutations, and testing the resulting mutants, to arrive at one or more of the instantly claimed combinations.
Applicant’s argument that the instantly claimed combinations of mutations amount to surprising and unexpected has been considered, however these arguments are not persuasive, because Applicant has not provided or cited to convincing evidence of the criticality of these substitutions. When considering the results of Table 2, it is noted that multiple combinations of substitutions, including many substitutions that are taught in Beier and Oestergaard, result in improved stability. There is no rationale underpinning the unexpected results of the instantly claimed combinations, compared to unclaimed combinations, such as the T65V, T127V, and G149N combination having a half-life improvement factor of 5.43 (see row 8 of Table 2). Further, these are only one of the conditions in which the combinations of mutations are tested, and such conditions are not required of the instant claims (drawn broadly to the enzyme variant).
Table 3 describes the half-life improvement factor of DNase variants in a “heavy-duty liquid detergent” and again, there is no evidence of criticality for the instantly claimed mutations, compared to the other combinations (e.g. the unclaimed substitutions of T65I+L181S, only having two mutations, in row 16; or the combination of T65V+ G149N+ L181E, in row 10).
Thus, the rejections of claims 21 and 24-38 as being obvious over Beier et al. (US 20190256831) and/or further in view of Oestergaard et al. (US 20190127664) are maintained.
Nonstatutory 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 21, 24-27 and 30-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 10,774,293. Although the conflicting claims are not identical, they are not patentably distinct from each other because the scope of the '293 claims anticipates or renders obvious that of the instant claims.
Claim 1 of the reference patent recites a DNase variant polypeptide comprising one or more substitutions selected from an extensive list compared to SEQ ID NO: 1, wherein the variant has an amino acid sequence identity to the parent polypeptide of at least 90%, and the variant has DNase activity. Claim 2 of the reference patent recites additional substitutions including N61D, T65I, T65V, and S82R. SEQ ID NO:1 of the reference patent claims is approximately 87% identical to the instantly claimed sequence, and the substitutions are the same, thus the mutated variant sequence would predictably fall within the sequence identity claimed in the instant claims (i.e. at least 80% in claim 21).
The difference in the instant claim and the reference claims is that the instant claims require T65I and two additional mutations and the recited Markush groups of substitutions are different. Regardless, each of these features is encompassed by or is obvious over the instant claims, as the T65I mutation is recited in reference claim 2 along with two or more of the instantly claimed substitutions (e.g. N61D and S82R). The Markush group of alternative substitutions recited in the '293 claims overlaps that of the instant claims.
Further, the reference claims are comprising-type claims and have at least one or more substitutions, and claim 9 of the reference patent recites that the total number of amino acid substitutions compared to SEQ ID NO: 1 is 1-20. Therefore, the instantly claimed variants and the claimed features are obvious over the reference patent claims.
The instant claims 24-26 further limit the sequence identity to the instant variant sequence of SEQ ID NO:1, but it is evident that these variants are encompassed by the reference claims, encompassing variants having multiple substitutions compared to the wild-type parental sequence referenced therein and up to 20 different mutations. Thus, from a comparison of SEQ ID NO:1 in the instant application to that of the reference sequence, it is evident that a sequence encompassed by the reference claims having multiple mutations (up to 20) would fall under the claimed variants of at least 95% sequence identity to the instantly recited SEQ ID NO:1.
Instant claim 27 recites additional mutations, and combinations of mutations, that fall within or would have been obvious in view of the claimed subject matter of the ‘293 patent. See e.g. the mutations of “Q14R”, “D56I”, “D56L”, “S68L”.
The instant claims 30-31 recite that the variants have 5 or more, or 15-18 of the amino acid residues in the recited positions. These positions correspond to specific substituted residues recited in reference claims 1 and 2 (e.g. those of T1I, S13Y, T22P, et cetera), and the reference subject matter includes variants having up to 20 mutations (see reference claim 9). Thus, the reference claims encompass variants according to the recitations of claims 30 and 31.
The specific positions recited in claim 32 correspond to many of the unmutated positions of the sequence in the reference claims (see e.g. T1I, S13Y, T22P, et cetera), thus variants comprising the same residues at the indicated positions are encompassed by the reference claims.
Regarding newly added claim 33, each of the recited mutations - N61D, T65I, and S82R- are encompassed by the recited subject matter of the reference patent as described above. Thus, these would all have been encompassed by the DNA variants disclosed therein.
Claims 21, 24-27, and 30-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 10,781,408. Although the conflicting claims are not identical, they are not patentably distinct from each other because the scope of the '408 claims anticipates or renders obvious that of the instant claims.
Claim 1 of the reference patent recites a variant of a DNase parent, which compared to a DNase with SEQ ID NO: 1, comprises two or more substitutions selected from an extensive list, wherein the variant has a sequence identity to the polypeptide shown in SEQ ID NO: 1 or SEQ ID NO: 28 of at least 90% and wherein the variant has DNase activity. Claim 11 of the reference patent recites additional substitutions including T65I, T65V, S82R, and N61D.
SEQ ID NO:1 of the reference patent is approximately 87% identical to the instantly claimed sequence (Appendix A below), and the substitutions are the same, thus the mutated variant sequence would predictably fall within the sequence identity claimed in the instant claims (i.e. at least 60% in claim 21). Further, SEQ ID NO:28 of the reference patent is 96.5% identical to that of the instantly recited SEQ ID NO:1 (Appendix B below). The instant claims are comprising-type claims and may include additional substitutions.
The difference in the instant claim and the reference claims is that the instant claims require T65V/I and two additional mutations (three total) and the recited Markush groups of substitutions are different. Regardless, each of these features is encompassed by or is obvious over the instant claims, as the T65I mutation is recited in reference claim 11 along with two or more of the instantly claimed substitutions (e.g. also including both N61D and S82R). The Markush group of alternative substitutions recited in the reference claims 1 and 11 overlap with those of the instant claims. Therefore, the instantly claimed variants and the claimed features are obvious over the reference patent claims.
The instant claims 24-26 further limit the sequence identity to the instant variant sequence of SEQ ID NO:1, but it is evident that these variants are encompassed by the reference claims, encompassing variants having multiple substitutions. From the comparisons of SEQ ID NO:1 in the instant application to that of SEQ ID NO:1 and SEQ ID NO:28 in the reference sequence, it is evident that a sequence encompassed by the reference claims having multiple mutations falls under the claimed variants of at least 95% sequence identity to the instantly recited SEQ ID NO:1.
Instant claims 27-29 and 32 recite additional mutations, and combinations of mutations, that fall within or would have been obvious in view of the claimed subject matter of the ‘408 patent. See e.g. the mutations of “Q14R”, “D56I”, “D56L”, “S68L”. The reference claims also recite substitutions such as “Y77T”, “Q109R”, and “S116D”, which are opposite of the instant claims, but thus encompass those variants having Y77, Q109 and S116 residues, which are structurally identical to the substitutions of the claimed variants.
The instant claims 30-31 recite that the variants have 5 or more, or 15-18 of the amino acid residues in the recited positions. These positions correspond to specific substituted residues recited in reference claims 1 and 2 (e.g. those of T1I, S13Y, T22P, S25P, et cetera). SEQ ID NO:28 of the reference claims includes 14 of these specified residues, and claims 1 and 11 recite the other 4 substitutions which are missing (i.e. S25P, S39P, T77Y, S181L). Thus, the reference claims encompass variants according to the recitations of claims 30 and 31.
The specific positions recited in claim 32 correspond to many of the unmutated positions of the sequence in the reference claims (see e.g. T1I, S13Y, T22P, et cetera), thus variants comprising the same residues at the indicated positions are encompassed by the reference claims.
Regarding newly added claim 33, each of the recited mutations - N61D, T65I, and S82R- are encompassed by the recited subject matter of the reference patent. Thus, these would all have been encompassed by the DNA variants disclosed therein.
Claims 21, 24-27, and 30-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 11 of U.S. Patent No. 11,447,723. Although the conflicting claims are not identical, they are not patentably distinct from each other because the scope of the '723 claims anticipates or renders obvious that of the instant claims.
Claim 1 of the reference patent recites a variant of a DNase parent, which compared to a DNase with SEQ ID NO: 1, comprises one or more substitutions selected from an extensive list, which includes N61D, T65I, T65V, S82R, and K107Q, wherein the variant has a sequence identity to the polypeptide shown in SEQ ID NO: 1 of at least 80% and the variant has DNase activity. Claim 4 of the reference patent recites that total number of alterations compared to SEQ ID NO: 1 is 1-20. SEQ ID NO:1 of the reference patent is approximately 87% identical to the instantly claimed sequence (Appendix A below), and the substitutions are the same, thus the mutated variant sequence would predictably fall within the sequence identity claimed in the instant claims (i.e. at least 60% in claim 21). Further, Claim 11 of the reference patent recites the mutations K107Q and T127S, among others.
The difference in the instant claim and the reference claims is that the instant claims require T65I and two additional mutations (three total) and the recited Markush groups of substitutions are different. Regardless, each of these features is encompassed by or is obvious over the instant claims, as the T65I mutation is recited in reference claims 1 and/or 11 along with two or more of the instantly claimed substitutions (e.g. N61D, S82R, and/or K107Q). The Markush group of alternative substitutions recited in the reference claim 1 overlaps with that of the instant claims. Therefore, the instantly claimed variants are obvious over the subject matter of the reference patent claims.
The instant claims 24-26 further limit the sequence identity to the instant variant sequence of SEQ ID NO:1, but it is evident that these variants are encompassed by the reference claims encompassing variants having multiple substitutions. A DNase variant according to the reference claims having multiple mutations, including those specified, encompasses the claimed variants having at least 95% sequence identity to the instantly recited SEQ ID NO:1 (when the specific mutations are applied to the reference SEQ ID NO:1).
Instant claim 27 recite additional mutations, and combinations of mutations, that fall within or would have been obvious in view of the claimed subject matter of the ‘723 patent. See e.g. the mutations of “Q14R”, “D56I”, “D56L”, “S68L” in claim 1. The reference claim 1 also recites substitutions such as “Y77T”, “Q109R”, “S116D” and “S181L”, which are opposite of the instant claims, but thus encompass those variants having Y77, Q109, S116, and S181 residues, which are structurally identical to the substitutions of the claimed variants.
The specific positions recited in claim 32 correspond to many of the unmutated positions of the sequence in the reference claims (see e.g. T1I, S13Y, T22P, et cetera), thus variants comprising the same residues at the indicated positions are encompassed by the reference claims.
The instant claims 30-31 recite that the variants have 5 or more, or 15-18 of the amino acid residues in the recited positions. These positions correspond to specific substituted residues recited in reference claims 1 and 2 (e.g. those of T1I, S13Y, T22P, S25P, et cetera). Claim 1 of the reference patent recites additional substitutions including S25P, S39P, T77Y, S181L. Thus, the reference claims encompass variants according to the recitations of claims 30 and 31. Further, claim 4 indicates that the total number of mutations compared to SEQ ID NO:1 is up to 20 alterations, which would thus encompass the claimed variants, having the three substitutions required of the instant claim 21 and at least 15 more of the mutations (for a total of 18).
Regarding newly added claims 33-38, each of the recited mutations - N61D, T65I, S82R, K107Q, and T127S- are encompassed by the recited subject matter of the reference patent, when considering all of the mutations taught in claims 1 and 11. Thus, these would all have been encompassed by the DNA variants disclosed therein.
Claims 21, 24-27, and 30-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,441,136. Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of the '136 claims anticipates or renders obvious that of the instant claims.
Claim 1 of the reference patent recites a variant of a DNase parent, which compared to a DNase with SEQ ID NO: 1, comprises two or more substitutions selected from an extensive list, which includes T127V, wherein the variant has a sequence identity to the polypeptide shown in SEQ ID NO: 1 or SEQ ID NO: 28 of at least 90% and wherein the variant has DNase activity. Claim 8 of the reference patent recites additional substitutions including N61D, T65I, S82R, and S181L. SEQ ID NO:1 of the reference patent is approximately 87% identical to the instantly claimed sequence (Appendix A below), and the substitutions are the same, thus the mutated variant sequence would predictably fall within the sequence identity claimed in the instant claims (i.e. at least 60% in claim 21). Further, SEQ ID NO:28 of the reference patent is 96.5% identical to that of the instantly recited SEQ ID NO:1 (Appendix B below).
The difference in the instant claim and the reference claims is that the instant claims require T65I and two additional mutations (three total) and the recited Markush groups of substitutions are different. Regardless, each of these features is encompassed by or is obvious over the instant claims, as the T65I mutation is recited in reference claim 8 along with two or more of the instantly claimed substitutions (e.g. at least N61D and S82R). The Markush group of alternative substitutions recited in the reference claims 1 and 8 overlap with those of the instant claims. Therefore, the instantly claimed variants and the claimed features are obvious over the reference patent claims.
The instant claims 24-26 further limit the sequence identity to the instant variant sequence of SEQ ID NO:1, but it is evident that these variants are encompassed by the reference claims, encompassing variants having multiple substitutions. From the comparisons of SEQ ID NO:1 in the instant application to that of SEQ ID NO:1 and SEQ ID NO:28 in the reference sequence, it is evident that a sequence encompassed by the reference claims having multiple mutations falls under the claimed variants of at least 95% sequence identity to the instantly recited SEQ ID NO:1. Claim 7 recites that the DNase variant comprises 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or all of the mutations selected from the group consisting of: T1I, S13Y, T22P, S25P, S27L, S39P, S42G, S57W, S59V, V76L, Q109R, S116D, T127V, S144P, A147H, S167L and G175D, of which all of these mutations appears to result in a variant having at least 95% identity to that of the instantly recited SEQ ID NO:1.
Instant claims 27 and 32 recite additional mutations, and combinations of mutations, that fall within or would have been obvious in view of the claimed subject matter of the ‘136 patent. See e.g. the mutations of “Q14R”, “D56I”, “D56L”, “S68L”. The reference claims also recite substitutions such as “Y77T”, “Q109R”, and “S116D”, which are opposite of the instant claims, but thus encompass those variants having Y77, Q109 and S116 residues, which are structurally identical to the substitutions of the claimed variants.
The instant claims 30-31 recite that the variants have 5 or more, or 15-18 of the amino acid residues in the recited positions. These positions correspond to specific substituted residues recited in reference claims 1 and 2 (e.g. those of T1I, S13Y, T22P, S25P, et cetera). SEQ ID NO:28 of the reference claims includes 14 of these specified residues, and claims 1 and 11 recite the other 4 substitutions which are missing (i.e. S25P, S39P, T77Y, S181L). Thus, the reference claims encompass variants according to the recitations of claims 30 and 31. Further, a variant having all the mutations in claim 7 appears to result in at least 15 of the instantly recited substitutions (as in claim 31), and the additional mutations are taught in claim 8.
The specific positions recited in claim 32 correspond to many of the unmutated positions of the sequence in the reference claims (see e.g. T1I, S13Y, T22P, et cetera), thus variants comprising the same residues at the indicated positions are encompassed by the reference claims.
Regarding newly added claim 33, each of the recited mutations - N61D, T65I, and S82R- are encompassed by the recited subject matter of the reference patent (see e.g. claim 8). Thus, these would all have been obvious derivatives of the DNA variant disclosed therein.
Claim 21 and 24-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5-6, and 11-16 of copending Application No. 18/319,681.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference application encompass or render obvious all of the instantly claimed subject matter.
Claim 1 of the reference Application (‘681) recites a detergent composition comprising a DNase variant which compared to the polypeptide of SEQ ID NO: 1 comprises the substitution G149N together with at least one of the substitutions consisting of N61D, T65I, T65V, S82R, K107Q, T127S, T127V, S164D, and L181S, wherein the variant has at least about 85% sequence identity to SEQ ID NO: 1 and has DNase activity. Thus, the composition of the ‘681 application comprises the polypeptide (DNase) variant and the same mutations as the instant claims. .
It is noted that the instant claims are comprising claims and that the additional inclusion of G149N (as in the reference application) is encompassed by amended claim 27.
Regarding the instant claims 24-26, reference claims 11-14 further limit the sequence identity of the variant, compared to the reference sequence (i.e. that of SEQ ID NO:1). Further, SEQ ID NO:1 of application 18/319,681 is 100% identical to that of the instant SEQ ID NO:1 (see Appendix C below). Thus the variant DNase of the ‘681 application encompasses a sequence and substitutions identical to those recited herein.
Regarding claim 27, reference claim 3 recites that the DNase variant further comprises at least one substitution comprising Q14R, Q14W, K21L, P25S, L33K, Q48D, D56I, D56L, S66Y, S68L, Y77T, S102Y, S106A, R109Q, R109T, D116S, D116W, T171W, L181T, or L181W, or a combination thereof, including many of the mutations encompassed by the instant claim 27. Further, amended claim 27 includes G149N, which is required of the amended reference claim 1.
Regarding the instant claims 28 and 29, the recited Markush groupings of possible combination sets appear to substantially overlap between those of the reference claims 5 and 6. Although not identical, these groups of possible combination sets encompass similar subject matter. Further, the combination of “N61D+T65I+S82R+K107Q” (recited in both claims 28 and 29) would have been an obvious combination to arrive at in view of all of the disclosed mutations in claims 1 and 3 of the reference patent. Further, even in claims 28 and 29, the DNase variant comprises a set of substitutions, but this language, under the B.R.I. does not exclude additional mutations (e.g. such as the G149N). Thus, claims 28 and 29 would have been obvious variants in view of the recited subject matter in the ‘681 application.
Regarding claims 30 and 31, reference claim 15 recites that the variant comprises at least 5 of the indicated amino acid residues in the following positions: I in position 1, Y in position 13, P in position 22, P in position 25, L in position 27, P in position 39, G in position 42, W in position 57, V in position 59, L in position 76, Y in position 77, R in position 109, D in position 116, P in position 144, H in position 147, L in position 167, D in position 175 and L in position 181. At least 5 encompasses the instantly claimed amount of 15-18 in claim 31, as all 18 positions of reference claim 15 could be the indicated residues.
Regarding instant claim 32, claim 16 of the reference application recites that the variant comprises one or more additional substitutions selected from I1T, Y13S, P22T, P25S, L27S, P39S, G42S, W57S, V59S,L76V, Y77T, R109Q, D116S, P144S, H147A, L167S and D175G, which is the same Markush group as instantly recited.
Regarding newly added claims 33-38, each of the recited mutations - N61D, T65I, S82R, K107Q, and T127S- are encompassed by the recited subject matter of the reference application (see e.g. reference claim 1). Thus, all of these mutations are found to be overlapping the DNase variants and mutants disclosed in the claimed subject matter of the ‘681 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. It is noted that the ‘681 application has an earlier filing date (05/18/2023) than the instant application, however both the ‘681 and the instant applications have the same International filing date (3/10/2022) and both claim benefit to an effective filing date of 3/15/2021.
Response to Arguments
Applicant's arguments regarding the non-statutory double patenting rejections, on pgs. 13-15 of the remarks filed 6/2/2026, have been fully considered but are not persuasive.
Applicant argues for each of the non-statutory double patenting rejections – over US Patent No. 10,774,293; US Patent No. 10,781,408; US Patent No. 11,447,723; and US Patent No. 11,441,136 – that the indicated patents correspond to or are related to Beier et al. (US 20190256831) and/or Oestergaard et al. (US 20190127664), and thus the same arguments given for the rejections under 35 U.S.C. § 103 are applicable to the non-statutory double patenting rejections. This is not found persuasive because these arguments do not particularly point out how the instantly claims are patentably distinct from the claimed subject matter of the reference patents. No specific arguments pertaining to the non-statutory double patenting rejections are provided. The argument related to the findings of obviousness of the publications Beier et al. (US 20190256831) and/or Oestergaard et al. (US 20190127664) is found insufficient for all of the reasons discussed above.
The subject matter of the instant claims have been deemed to be either anticipated or rendered obvious by the claimed subject of the reference patents, for all of the reasons previously set forth. Because Applicant’s arguments fail to convincing demonstrate that the instant claims are patentably distinct from the indicated claims of US Patent No. 10,774,293; US Patent No. 10,781,408; US Patent No. 11,447,723; US Patent No. 11,441,136, the rejections are maintained.
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome these rejections based on nonstatutory double patenting. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
Regarding the outstanding provisional rejection of claims 21-32 over claims 1-16 of U.S. Application No. 18/319,681, Applicant’s arguments have been fully considered, however the rejection is maintained.
The petition under 37 C.F.R. 1.183, filed 6/2/2026, was reviewed and dismissed. The Terminal Disclaimer filed 6/2/2026 based on a joint research agreement (JRA TD) filed under 37 CFR 1.321(d) was disapproved in view of the deficiencies set forth in the 9/11/2026 petition decision. See the communication mailed 9/11/2026 concerning the incorrect identification of the reference application as a reference patent, and the suggested language for a proper terminal disclaimer. Because the terminal disclaimer was not approved, the provisional non-statutory double patenting rejection over Application No. 18/319,681 is maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new and modified grounds 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 ANDREW TERRY MOEHLMAN whose telephone number is (571)270-0990. The examiner can normally be reached M-F 9am-5pm EST.
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, Anand Desai can be reached at 571-272-0947. 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.
/A.T.M./Examiner, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
