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 .
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 (i.e., changing from AIA to pre-AIA ) 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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/21/2025 has been entered.
Status of Claims
Claims 1-2, 4, and 7-14 are pending. Claims 3 and 5-6 are canceled. Claims 7-13 are drawn to the nonelected invention. Claim 14 is new. Claims 1-2, 4 and 14 are under examination.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
New Rejection
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, 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 1-2, 4 and 14 are rejected under 35 U.S.C. 103 as being obvious over Hatayama et al. (WO2018056374, filed 09/21/2017; note that the cited passages are from US11414475B2 counterpart, as WO2018056374 is not an English document) in view Hatayama et al. (US2013/0079499A1, published 03/28/2013, of record 892 dated 11/22/2024, hereinafter Hatayama II).
The applied reference, WO2018056374, has a common Applicant and joint inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
With respect to claim 1, and Hatayama teaches improving productivity and thermal stability derived from human Fc receptor that has binding affinity for IgG and the improved recombinant FcγRIIa comprising at least the amino acid residues from position 29 to position 201 of the amino acid sequence set forth in SEQ ID NO: 88 wherein the substitutions of (7) to (12) are included in the amino acid residues from position 29 to position 201 to produce SEQ ID NO: 89 (see below; at col. 1, lines 5-10; claim 1; and Table 19). Therefore, it would read on the recited element (i) of amino acids modifications at the 6 positions. Hatayama further teaches that as long as affinity for IgG is maintained, the improved recombinant FcγRIIa consisting of amino acid residues in a region other than positions substituted by the substitutions (7) to (12) have been deleted, substituted or added (at col. 12, lines 20-31 and col. 13, lines 25-30 and 55-61). Additionally, Hatayama teaches between FcγRIIa and FcγRIIb are highly homologous with a difference of only 12 amino acids residues and the specific differing locations are shown in Fig. 4 and these amino acid sequences are highly conserved (at col. 12, lines 54-62). In particular, Fig. 4 has shown that one of the positions that is different is at position 191.
Note that the instant claimed SEQ ID NO: 2 is 100% match with SEQ ID NO: 88 of Hatayama.
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(Emphasis added for positions 68, 80, 84, 90, 91, and 125)
SEQ ID NO: 89 reads on an Fc-binding protein comprising at least amino acid residues from glutamine at position 29 to glutamine at position 201 of the amino acid sequence set forth in SEQ ID NO: 2 with the proviso that the Fc-binding protein is modified with element (i) of the instant claim 1.
Although Hatayama teaches improved recombinant FcγRIIa may have additional substitutions of amino acids in a region other than the positions in element (i), Hatayama does not explicitly teach additional amino acid modifications as recited in element (ii).
Hatayama II teaches Fc binding protein having increased thermal stability with respect to heat, acid, and/or alkalinity compared with the wild type and (at abstract, and paras. [0001] and [0028]). Hatayama II teaches the Fc receptor can be further classified into subtypes and it has been reported that FcγRI, FcγRIIa, FcγRIIb, and FcγRIII exist as receptors for IgG (at para. [0002]). Hatayama II teaches when the Fc binding protein of the present embodiment is produced by causing the amino acid substitution, the amino acid at a specific position may be substituted by an amino acid other than that in the substitution described above as long as the Fc binding protein has the antibody binding activity (at para. [0070]). In particular, Hatayama II teaches the Fc binding protein sequence substitutions are within a recognized region such as from glutamine at position 16 to valine at position 289 in the amino acid sequence and the substitutions are at positions 19-20, 46-47, 49-53, 57-58, 60-65, 69-70, 69-70, 88-90, 102-103, 114-115 (at para. [0067]). Hatayama II teaches screening of Fc binding protein with improved stability by about 2,5000 transformants were evaluated (at paras. [0140]-[0141], Example 6). Hatayama II teaches screening by substituting amino acids within the established sequence range and the number of the amino acid to be substituted is not particularly limited (for example, at paras. [0067]-[0071], Tables 6 and 10-11, and Example 17). For example, Hatayama II teaches substitution pairs between Thr and IIe, Leu and Gln, Pro and Leu, Leu and Ser, Pro and Gln, Pro and Thr, Asn and Ser, Leu and His were made (at paras. [0067], [0072]). Hatayama II teaches mutation introduction into Fc binding protein and production of library with a mutation was randomly introduced into the polynucleotide encoding the Fc binding protein (for example, at paras. [0132], [0207], [0210]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the improved recombinant Fc binding protein (SEQ ID NO: 89) of Hatayama through screening substitutions as taught by Hatayama II because (1) Hatayama and Hatayama II both recognize substitutions within a defined region have improved productivity and thermal stability, (2) Hatayama has established amino acid positions for substitution within glutamine at position 29 to glutamine at position 201, and (3) Hatayama II teaches as long as affinity for IgG is maintained, other positions may be substituted that produce a library of mutated protein activity for screening improved recombinant Fc binding proteins. Because Hatayama teaches specific positions have been mutated within the region of 29 to 201 for improvement in its recombinant Fc binding protein and Hatayama II teaches random mutations are performed to produce a library for screening Fc binding protein’s activities, it would have been obvious to the person to have further mutated nearby amino acid residues from the established positions as starting positions to produce a library of mutated Fc binding proteins that measures functional activities, as Hatayama has already established positions of 68, 80, 84, 90, 91, and 125 as improvement sites.
Furthermore, the improved Fc binding protein comprising SEQ ID NO: 89 of Hatayama is a series of amino acid substitutions from SEQ ID NO: 88. Meanwhile, Hatayama II recognizes that substitutions of Fc binding proteins also contain substitutions at adjacent positions to screen for thermal stability. Therefore, it would have been obvious to have substituted position 69 of SEQ ID NO: 89 of Hatayama with leucine because Hatayama has substituted position 68 and found that it improves function and chemical substitutions between glutamine and leucine are recognized structures for producing libraries that evaluate thermal stability of Fc binding proteins, as taught by Hatayama II.
The person would have a reasonable expectation of success in substituting recognized amino acid structures within the defined region of SEQ ID NO: 89 because it has been well understood by Hatayama that the improved Fc binding protein comprising SEQ ID NO: 89 is from a series of amino acid substitutions. Additionally, it has been recognized in the art to produce libraries that measure functional activity from substitutions and adjacent positions are recognized positions for mutations in screening activities, as taught by Hatayama (positions 90-91) and Hatayama II.
With respect to claims 2 and 4, Hatayama teaches between FcγRIIa and FcγRIIb are highly homologous with a difference of only 12 amino acids residues and the specific locations are shown in Fig. 4 and these amino acid sequences are highly conserved (at col. 12, lines 54-62). In particular, Fig. 4 has shown that one of the positions that is different is at position 191. As stated above, Hatayama teaches as long as affinity for IgG is maintained, amino acids residues in a region other than the position substituted may be substituted (at col. 12, lines 22-32). However, Hatayama does not explicitly teach a substitution of leucine to serine at position 190 in claims 2 or 4 (SEQ ID NO: 5 of claim 4).
It would have been obvious to have individually substituted positions at 190-192 of SEQ ID NO: 89 because Hatayama discloses FcγRIIa and FcγRIIb are highly homologous with a difference of only 12 amino acids residues including position 191. As stated above, substitutions at adjacent positions are recognized for screening functional activity. Thus, the person would have individually modified at positions 190, 191, and 192 to see the functional effect and whether such mutations impact functional activity, as position 191 is non-conserved in a protein that is highly homologous. Additionally, it would have been obvious to have replaced leucine with serine at position 190 because it has been recognized in the art to substitute between Leu and Ser for producing a library that screens for functional activity, as taught by Hatayama II.
With respect to claim 14, Hatayama does not teach together substitutions of leucine to serine at position 190 and glutamine and leucine at position 69. As stated above, it would have been obvious to have substituted position 69 of SEQ ID NO: 89 of Hatayama with leucine because the improved Fc binding protein comprising SEQ ID NO: 89 of Hatayama is from multiple amino acid substitutions including position 68 from SEQ ID NO: 88 for thermal stability. Meanwhile, chemical substitutions between glutamine and leucine are recognized structures of Hatayama II for producing the library that screens for functional activities of Fc binding proteins.
Because Hatayama teaches multiple substitutions produce the improved Fc binding protein comprising SEQ ID NO: 89, it would have been obvious to have individually incorporated a substitution at positions 190-192 of SEQ ID NO: 89 for screening functional activity, as position 191 of SEQ ID NO: 89 has been recognized as not being conserved in proteins that are highly conserved. Hatayama and Hatayama II recognize substitutions at adjacent positions for screening thermal stability. As stated above, the person would have modified at positions 190, 191, or 192 in combination with adjacent positions of the established mutations to see the functional effect and whether such combination impacts functional activity, as Hatayama’s purpose is to identify improved recombinant Fc binding proteins from a defined region. Additionally, it would have been obvious to have replaced leucine with serine at position 190 because it has been recognized in the art to substitute between Leu and Ser for producing a library that screens for thermal stability, as taught by Hatayama II.
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 1-2, 4 and 14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11414475B2 (‘475) (of record 892 dated 03/21/2024) in view of Hatayama et al. (WO2018056374, filed 09/21/2017; note that the cited passages are from US11414475B2 counterpart, as WO2018056374 is not an English document) and Hatayama II (US2013/0079499A1, published 03/28/2013, of record 892 dated 11/22/2024).
U.S. Patent No. ‘475 recites in claim 1 an improved recombinant Fc gamma RIII wherein the improved recombinant Fc gamma RIII comprises at least the amino acid residues from position 29 to position 201 the amino acid sequence set forth in SEQ ID NO: 88, wherein at least one of the following amino acid substitutions (7) to (12) are included in the amino acid residues from position 29 to position 201: (7) a substitution of valine for isoleucine at position 68 of SEQ ID NO: 88; (8) a substitution of glutamine for histidine at position 80 of SEQ ID NO: 88; (9) a substitution of threonine for serine at position 84 of SEQ ID NO: 88; (10) a substitution of threonine for asparagine at position 90 of SEQ ID NO: 88; (11) a substitution of serine for asparagine at position 91 of SEQ ID NO: 88; (12) a substitution of arginine for histidine at position 125 of SEQ ID NO: 88; (iii) improved recombinant FcγRII consisting of an amino acid sequence of the improved recombinant FcγRII of the above (i) or (ii) in which one or more amino acid residues in a region other than positions substituted by the substitutions (1) to (12) have been deleted, substituted or added, and having affinity for IgG. Dependent Patent claim 3 recites the improved recombinant FcγRIIa comprising at least the amino acid residues from position 29 to position 201 of the amino acid sequence set forth in SEQ ID NO: 89.
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Even though Patent ‘475 recite substitutions (7) to (12) and substitutions in a region other than positions substituted and SEQ ID NO: 89, the Patent does not explicitly recite modified at least one of the modifications indicated in (1) to (12) of element (ii). Hatayama and Hatayama II have been discussed above.
It would have been obvious to the person at the time of filing to have further mutated SEQ ID NO: 88 as recited in Patent claim 1 or SEQ ID NO: 89 as recited in Patent claim 3 of ‘475 with amino acid substitutions as taught by Hatayama II for measuring mutated Fc binding proteins’ activity because (1) Patent ‘475 recites amino acid substitutions at positions 68, 80, 84, 90, 91, and 125 have improved recombinant Fc binding protein, (2) the Patent also recites the ability to substitute at other positions within glutamine at position 29 to glutamine at position 201; and (3) Hatayama II recognizes that substitutions for improving Fc binding protein also contain random substitutions at adjacent positions to screen for improvement in Fc protein’s activity. Because Patent ‘475 recites a defined region for improving Fc binding protein within its sequence, Hatayama teaches specific positions have been mutated within the region of 29 to 201 for improvement in its recombinant Fc binding protein and Hatayama II teaches random mutations are performed to produce a library for screening Fc binding protein’s activities, it would have been obvious to the person to have further mutated nearby amino acid residues from the established positions of the recited Patent ‘475 to produce a library of mutated Fc binding proteins that measures functional activities, as Patent and Hatayama have already established positions of 68, 80, 84, 90, 91, and 125 as improvement sites.
The person would have a reasonable expectation of success in substituting recognized amino acid structures within the defined region of SEQ ID NO: 89 as recited by Patent ‘475 because it has been well recited by the Patent that the improved Fc binding protein comprising SEQ ID NO: 89 is from a series of amino acid substitutions. Additionally, it has been recognized in the art to produce libraries that measure functional activity from substitutions and adjacent positions are recognized positions for mutations in screening activities, as recited by Patent ‘475 (positions 90-91), and as taught by Hatayama (positions 90-91) and Hatayama II.
The instant claims 2 and 4, Patent ‘475 does not recite a substitution of leucine to serine at position 190 of SEQ ID NO:2 (claim 2) or the instant claimed SEQ ID NO: 5 (claim 4).
It would have been obvious to have individually substituted positions at 190-192 of SEQ ID NO: 89 as recited in Patent ‘475 because Hatayama discloses FcγRIIa and FcγRIIb are highly homologous with a difference of only 12 amino acids residues including position 191. As stated above, substitutions at adjacent positions are recognized for screening functional activity. Thus, the person would have individually modified at positions 190, 191, and 192 to see the functional effect and whether such mutations impact functional activity, as position 191 is non-conserved in a protein that is highly homologous. Additionally, it would have been obvious to have replaced leucine with serine at position 190 because it has been recognized in the art to substitute between Leu and Ser for producing a library that screens for functional activity, as taught by Hatayama II.
The instant claim 14, Patent claim 3 recites SEQ ID NO: 89 but Patent ‘475 does not recite a substitution of leucine to serine at position 190 and a substitution of glutamine to leucine at position 69 of SEQ ID NO:2.
It would have been obvious to have substituted position 69 of SEQ ID NO: 89 as recited in Patent ‘475 with leucine because the improved Fc binding protein comprising SEQ ID NO: 89 of the Patent is from multiple amino acid substitutions including position 68 of SEQ ID NO: 88. Meanwhile, chemical substitutions between glutamine and leucine are recognized structures of Hatayama II for producing the library that screens for functional activity of Fc binding proteins.
Because the Patent ‘475 recites multiple substitutions to improve Fc binding protein, it would have been obvious to have individually incorporated a substitution at positions 190-192 of SEQ ID NO: 89 for screening functional activity, as position 191 of SEQ ID NO: 89 has been recognized as not being conserved in proteins that are highly conserved. Patent ‘475, Hatayama and Hatayama II recognize substitutions at adjacent positions for improvement. As stated above, the person would have modified at positions 190, 191, or 192 in combination with adjacent positions of the established mutations to see the functional effect and whether such combination impacts functional activity, as Patent ‘475’s purpose is to identify improved recombinant Fc binding proteins from a defined region. Additionally, it would have been obvious to have replaced leucine with serine at position 190 because it has been recognized in the art to substitute between Leu and Ser for producing a library that screens for functional activity, as taught by Hatayama II.
Response to Arguments
Applicant's arguments filed 04/21/2025 have been fully considered but they are not persuasive. Although the 103 rejection is newly rejected in light of WO2018056374 having a filing date of 09/21/2017, the arguments will be addressed concurrently with the pending nonstatutory double patenting rejection, as Hatayama (WO2018056374) and Patent No. ‘475 are counterparts.
Initially, Applicant requests acknowledgment of foreign priority. As stated above, receipt is acknowledged.
Applicant argues on page 9 of the Remarks that Patent ‘475 provides no guidance and Hatayama teaches a different subtype FcγR1 than Patent ‘475. At most, with respect to the claims of Patent ‘475 that the person having ordinary skill in the art would only have a general suggestion to modify SEQ ID NO: 88 at positions other than positions 68, 80, 84, 90, 91, and 125. SEQ ID NO:88 (positions 29-201) is 172 residues long. At each of these, 19 possible substitutions could be made in view of Patent ‘475. As such, when considering only a single additional substitution beyond positions 68, 80, 84, 90, 91,and 125, there are 3154 possible modified Fc binding proteins. Applicant further argues, bottom of page 9 to page 10, that simply because an amino acid (for example, position 68) is modified is not a sufficient reason to modify an adjacent amino acid (for example, position 69). Even if it would have been obvious to modify glutamine at position 69, there is no reason why it would have been obvious to modify this to leucine specifically. Patent ‘475 and Hatayama do not provide any comments to suggest that one make further modifications starting with positions adjacent to already-modified positions. Furthermore, no art has been cited to demonstrate this point. Applicant argue, bottom of page 10, Applicant argues that it would not have been obvious to select on of the possible modifications (such as part 3 or part 4 of claim 1) from among these 190 possibilities. In particular, it could not be reasonably predicted which embodiments would have improved residual activity.
Applicant argues on pages 11-12 that evidenced by Appendix A and Asaoka conclude that by introducing a mutation adjacent to a known mutation does not necessarily result in a protein having the desired activity. It is clear that it is also necessary to specify the type of amino acid to be the mutation target. In actuality, it is very difficult to determine which amino acid of which position should be mutated to which amino acid of which type. Applicant argues on page 13 that the person would not anticipate a positive outcome from the modification without testing the results. Applicant argues that “obvious to try” rationale allows for choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. A proposed modification cannot be obvious where there is not a reasonable expectation of success, as a positive outcome would not have been anticipated.
The arguments are not found persuasive for the following reasons.
Hatayama (WO2018056374) and Patent No. ‘475 provide a blueprint to modify within a defined region (positions 29 to 201) for Fc binding protein’s activity. In particular, additional substitutions to SEQ ID NO: 89 are not hindsight because to get to SEQ ID NO:89, substitutions at various positions (7) to (12) of SEQ ID NO: 88 were needed to obtain the improved the recombinant Fc binding protein. Meanwhile, these particular sites and the substituted amino acid residues would have not been identified as improved sites without being screened through functional activity. In other words, to identify whether the mutation provides functional improvement, a library of Fc binding proteins is functionally tested. Producing a library for measuring and screening mutated Fc proteins’ activity has been recognized in the art. Although Hatayama II teaches a different sequence of Fc binding protein than Hatayama (WO2018056374) and Patent No. ‘475, the process of identifying improved sites of Fc binding protein’s activity has been recognized in the art through substitutions and producing a library for said substitutions. Meanwhile Hatayama (WO2018056374) and Patent No. ‘475 both recognize and embrace positions 29 to 201 for improvement in recombinant Fc binding protein through its substitutions from SEQ ID NO: 88. Thus, it would have been obvious to the person to have used those previous mutation sites as starting points to screen for further improvements, as the Patent and Hatayama have already established positions of 68, 80, 84, 90, 91, and 125 as improvement sites. Meanwhile, chemical structures between substitutions, for example, glutamine and leucine are recognized structures for producing libraries that evaluate thermal stability of Fc binding proteins, as taught by Hatayama II. The person would recognize that when producing a library of mutants, it does not require all mutated positions to produce improved functionality but rather identify and correlate positions to function in a library of tested functions.
With respect to Appendix A and Asaoka (provided by Applicant), these references do provide evidence that functional activity has to be tested against the mutated protein to correlate structure and function. Meanwhile, the rejection is not based on mutating only sites that will improve Fc binding protein of Hatayama (WO2018056374) and Patent No. ‘475. The person would not be able to identify it without screening through a library. But rather, the rejection is based on using known structural substitutions with established mutation sites. It would have been obvious to the person to have further mutated nearby amino acid residues from the established positions as starting positions because Patent No. ‘475 and Hatayama (WO2018056374) have already established positions of 68, 80, 84, 90, 91, and 125 as improvement sites.
Applicant further argues on pages 14-15 that the amended claims 2, and 14 recite substitution at position 190 and the references do not include any modifications at position 190.
As stated above, Hatayama (WO2018056374) teaches between FcγRIIa and FcγRIIb are highly homologous with a difference of only 12 amino acids residues and the specific locations are shown in Fig. 4 and these amino acid sequences are highly conserved (at col. 12, lines 54-62). In particular, Fig. 4 has shown that one of the positions that is different is at position 191. Therefore, it would have been obvious to have individually substituted positions at 190-192 of SEQ ID NO: 89 as recited in Patent ‘475 because Hatayama discloses FcγRIIa and FcγRIIb are highly homologous with a difference of only 12 amino acids residues including position 191. Also, substitutions at adjacent positions are recognized for screening functional activity. Therefore, it would have been obvious to the person to have modified at positions 190, 191, or 192 in combination with position 69 to see the functional effect and whether such combination impacts functional activity, as position 191 is non-conserved in a protein that is highly conserved.
Conclusion
No claim is allowed.
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/N.P.N/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678