Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
The amendment filed March 2, 2026 in response to the Office Action of December 2, 2025 is acknowledged and has been entered.
Claims 95, 97, 98 and 105 have been amended.
Claim 101 has been cancelled.
Claim 115 has been added.
Claims 95-100 and 102-115 are pending.
Claims 107-114 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions or species, there being no allowable generic or linking claim.
Claims 95-100, 102-106, and 115 are currently under consideration as drawn to the elected invention.
The Kfir Oved’s Declaration under 37 CFR 1.132 filed March 2, 2026 is considered but it is insufficient to overcome the 103 rejection for claims 95-100, 102-106, and 115, see response to the argument following 103 rejection.
The 112(a), 112(b) and 112(d) rejections set forth in the previous Office Action are hereby withdrawn in view of Applicant’s claim amendments and arguments.
Priority
In view of Applicant’s argument, the priority date has been established as May 8, 2023 which is the filing date for U.S. Provisional Patent Application Nos. 63/464,673.
Information Disclosure Statement
The Information Disclosure Statement filed on 03/02/2026 has been considered and entered by examiner.
Specification
The disclosure is objected to because of the following informalities: in new Table 3, (GGGS)3 should be label with SEQ ID NO: 8, (EAAAK)2 should be labeled with SEQ ID NO: 14, and (EAAAK)4 should be labeled with SEQ ID NO: 15.
Appropriate correction is required.
MAINTAINED/MODIFIED 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 95-100, 102-106, and 115 are rejected under 35 U.S.C. 103 as being unpatentable over Song (Song et al., US 2021/0221869 A1, Publication Date: 07/22/2021, of record) in view of Zocher (Zocher et al., International Immunology, Vol. 15, No. 7, pp. 789-796, Publication Year: 2003, of record) and Saunders (Frontiers in Immunology, vol. 10, article 1296, Publication Date: 06/07/2019, cited in IDS of 09/30/2025, of record).
Song teaches a fusion protein comprising a TSHR fragment comprising an extracellular domain of a wild-type TSHR, and an immunoglobulin Fc region ([0001]), for example a fusion protein comprising an immunoglobulin Fc region bound to thyrotropin receptor (TSHR) fragments, such as a fragment from amino acid at position 21 to amino acid at position 282 of a TSHR, or shorter fragments of TSHR extracellular domain (Fig. 2, TR4-Fc, TR5-Fc, TR6-Fc, TR7-Fc, TR8-Fc and TR9-Fc).
Song teaches that the Fc region can be a human IgG1 Fc region ([0058], claim 4).
Song teaches that the Fc region can have a Fc region mutant having a substitution ([0054]).
Song teaches that the fusion protein comprises SEQ ID NO: 29 (claim 8, [0069]). SEQ ID NO: 29 comprises: a fragment of TSHR extracellular domain (e.g. positions: 21-282), a GS linker and a Fc ([0069]).
Song teaches that the Fc region comprise a hinge, CH2 and CH3, e.g. SEQ ID NO: 22 ([0052], claim 6). As evidenced by paragraph [0173] of the instant specification, Fc domain comprising a hinge, CH2 and CH3 domain is a dimerization domain. Thus, the fusion protein of Song (e.g. SEQ ID NO: 22) would form homodimers comprising two identical fusion peptides.
Song teaches that the fusion proteins (e.g. TR4-Fc) can neutralize autoantibodies (Example 2-2, [0131] and [0132]); the fusion protein (e.g. TR4-Fc) has TSH-blocking activity (Example 1-1 and 1-2 ; the fusion protein TR-GS (which is TSHR(21-282)-GS linker-Fc, see Table 4) has a remarkable autoantibody-neutralizing effect even at 5 μg/ml.
Song teaches that Graves' disease is an autoimmune disease caused by autoantibodies that induce over-production of thyroid hormone, that is, hyperthyroidism ([0003]).
Song teaches a method of treating Graves’ disease by administering a pharmaceutical composition comprising the fusion protein ([0017], claim 13).
Song’s teachings are described above. However, Song does not teach the Fc domain comprising a S267E mutation.
Zocher teaches that antigen-specific B cells are key players in many autoimmune disease through the production of autoreactive antibodies. Autoreactive antibodies can cause sever tissue damage and malfunction (Abstract).
Zocher teaches a design of Fc fusion protein with the potential to reduce antigen-specific antibody titers while, at the same time, depleting autoreactive B cells as the root cause of pathogenic autoantibodies (the bridging paragraph of pages 789-790; page 790, col. 1, para. 2; and the bridging paragraph of pages 794-795).
Zocher teaches the activation of MOC-Fc on autoreactive B cells is not restricted to resting B cells (Fig. 5), but also includes the active elimination of activated B cells and the reduction of circulating antibodies (Fig. 6) (see page 795, col. 1, para. 2).
Saunders teaches Fc-fusion antibody-like proteins have become successful biologics developed for treating various diseases. In general these biopharmaceuticals can be used for blocking protein:protein interaction, recruiting effector cells to targets, and fixing complement (Abstract).
Saunders teaches that the hinge and constant domains engage host receptors or complement protein to mediate of effector functions and regulate antibody circulation. The molecular details of these interactions have led to manipulation of the sequences and glycosylation of hinge and constant domains to enhance or reduce effector functions (Abstract).
Saunders teaches that changes to the sequence of the Fc and hinge region allows one to manipulate the effector functions of an antibody-like protein. And the optimization of antibody binding to FcγRs has been the major focus of the Fc engineered field (page 2, col. 2, para. 1).
Saunders teaches that Ser267Glu (S267E) substitution in the IgG1 Fc region results in more potent Complement-Dependent Cytotoxicity (CDC). The largest improvement in CDC activity was achieved when S267E, H268F and S324T (termed the EFT mutations) were combined. Correlation analyses suggested that the improvement in CDC potency was due to increased C1q binding (page 8, col. 1, para. 2). The triple EFT mutations had increased biding to the inhibitory FcγRIIb, which probably limited its ADCC and ADCP activity (Table 1; and page 8, col. 1, para. 2).
Saunders teaches that the addition of ADCC and ADCP enhancing mutations to the EFT mutations restored ADCC and ADCP function back to wild-type IgG1 levels(page 8, col. 1, para. 2).
Taken together, Saunders teaches the Fc variants comprising S267E mutation provide a range of effector function activities, such as enhanced CDC/decreased ADCC; or enhanced CDC/normal ADCC.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to make pharmaceutical composition comprising a fusion protein comprising an extracellular domain of a TSHR (e.g. amino acid positions 21-282), and an immunoglobulin Fc region as taught by Song, as evidenced by the instant specification, the fusion protein would form a homodimer with two identical fusion peptide; and to use the fusion protein to treat Graves’ disease caused by autoantibodies, as taught by Song, and to further modify the fusion protein by adding a S267E mutation in Fc region as taught by Zocher and Saunders, because Zocher teaches that Fc fusion protein can not only deplete circulating antibodies but also reduce autoreactive B cells responsive for autoantibody production through effector cytotoxicity (Figs. 4-6); and Saunders teaches various mutation combinations comprising S267E which results in a range of effector function activities, such as enhanced CDC/decreased ADCC; or enhanced CDC/normal ADCC. One of ordinary skill in the art would have had a reasonable expectation that the fusion protein with mutations comprising S267E, would have enhanced CDC activity, thus, enhanced activity to deplete specific B cells responsive for anti-TSHR autoantibody production. One of ordinary skill in the art would have had a reasonable expectation that the fusion protein with enhanced B-cell depletion activity would have enhanced therapeutic activity for treating Grave’s disease. The motivation would have been to expand options for Fc-fusion proteins with a range of effector functions and to develop a pharmaceutical composition with better therapeutic properties.
Regarding claim 96, Song teaches that the Fc region comprise a hinge, CH2 and CH3, e.g. SEQ ID NO: 22 ([0052], claim 6). As evidenced by paragraph [0173] of the instant specification, Fc domain comprising a hinge, CH2 and CH3 domain is a dimerization domain. Thus, the fusion protein would form homodimers comprising two identical fusion peptides.
Regarding claim 97, Song teaches that the Fc region can be a IgG1 Fc region (claim 4).
Regrading claim 98, Song teaches that the Fc region can be a human IgG1 Fc region ([0058], claim 4). As shown below, human IgG1 Fc comprise a domain that is 96.9% identical to SEQ ID NO: 53, see alignment below:
SEQ ID NO: 53 vs. human IgG1 Fc:
Query Match 96.9%; Score 1234; DB 1; Length 399;
Best Local Similarity 98.3%;
Matches 226; Conservative 2; Mismatches 2; Indels 0; Gaps 0;
Qy 1 EPKSCDKTHTCPPCPAPELLGGPCVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF 60
||||||||||||||||||||||| ||||||||||||||||||||||||||||||||||||
Db 99 EPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF 158
Qy 61 NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 159 NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT 218
Qy 121 ISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTP 180
||||||||||||||||||||:|:||||||| |||||||||||||||||||||||||||||
Db 219 ISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP 278
Qy 181 PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP 230
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 279 PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP 328
Regarding claims 99, 100 and 115, Song teaches a fragment of amino acid positions of 21-282 of TSHR. As shown below, SEQ ID NO: 1 corresponds to amino acid position of 21-413 of TSHR protein:
Query Match 100.0%; Score 2078; Length 764;
Best Local Similarity 100.0%;
Matches 393; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GMGCSSPPCECHQEEDFRVTCKDIQRIPSLPPSTQTLKLIETHLRTIPSHAFSNLPNISR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 GMGCSSPPCECHQEEDFRVTCKDIQRIPSLPPSTQTLKLIETHLRTIPSHAFSNLPNISR 80
Qy 61 IYVSIDVTLQQLESHSFYNLSKVTHIEIRNTRNLTYIDPDALKELPLLKFLGIFNTGLKM 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 IYVSIDVTLQQLESHSFYNLSKVTHIEIRNTRNLTYIDPDALKELPLLKFLGIFNTGLKM 140
Qy 121 FPDLTKVYSTDIFFILEITDNPYMTSIPVNAFQGLCNETLTLKLYNNGFTSVQGYAFNGT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 FPDLTKVYSTDIFFILEITDNPYMTSIPVNAFQGLCNETLTLKLYNNGFTSVQGYAFNGT 200
Qy 181 KLDAVYLNKNKYLTVIDKDAFGGVYSGPSLLDVSQTSVTALPSKGLEHLKELIARNTWTL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 201 KLDAVYLNKNKYLTVIDKDAFGGVYSGPSLLDVSQTSVTALPSKGLEHLKELIARNTWTL 260
Qy 241 KKLPLSLSFLHLTRADLSYPSHCCAFKNQKKIRGILESLMCNESSMQSLRQRKSVNALNS 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 261 KKLPLSLSFLHLTRADLSYPSHCCAFKNQKKIRGILESLMCNESSMQSLRQRKSVNALNS 320
Qy 301 PLHQEYEENLGDSIVGYKEKSKFQDTHNNAHYYVFFEEQEDEIIGFGQELKNPQEETLQA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 321 PLHQEYEENLGDSIVGYKEKSKFQDTHNNAHYYVFFEEQEDEIIGFGQELKNPQEETLQA 380
Qy 361 FDSHYDYTICGDSEDMVCTPKSDEFNPCEDIMG 393
|||||||||||||||||||||||||||||||||
Db 381 FDSHYDYTICGDSEDMVCTPKSDEFNPCEDIMG 413
Thus, the fragment taught by Song reads on a fragment of an extracellular domain of TSHR comprising SEQ ID NO: 1 (comprising a fragment of SEQ ID NO: 1).
Regarding claims 102-104, Song teaches various fusion protein with smaller fragment of the extracellular domain, such as TR5-Fc, TR6-Fc, TR8-Fc and TR9-Fc all of them have less than 260 amino acid fragments.
Regarding claim 105, Song teaches the fragment and Fc separated by a linker (Fig. 4), and TR-GS fusion protein which has a linker between the fragment and Fc domain (Table 4).
Regarding claim 106, Song teaches a pharmaceutical composition comprise a therapeutically effective amount of the fusion protein and a pharmaceutically acceptable carrier ([0091]).
Response to Arguments
For the 103 rejection of claims 95-100, 102-106, and 115, Applicant argues:
Song teaches a molecule with "autoantibody-neutralizing ability". Every figure of Song recites that the autoantibodies are "neutralized". The meaning of neutralization is that once the antibodies have bound the fragment of TSHR in the molecule they are no longer available to bind endogenous TSHR and thus are neutralized. The inclusion of the S267E mutation does not enhance autoantibody binding and thus is not relevant to neutralization.
Zocher is concerned with the depletion of primary autoreactive B-cells. Autoantibody titers are reduced in vivo because of the reduction in the number of B cells. Zocher teaches that their molecule does not completely eliminate autoreactive B cells or autoantibodies in vivo.
Saunders teaches that the S267E mutation increases complement-dependent cytotoxicity (CDC) activity. CDC refers to the immune mechanism whereby antibodies bind surface antigens and activate the complement cascade. This leads to the formation of membrane attack complex on the cell which produces holes in the cell membrane resulting in cell lysis.
Applicant’s arguments have been fully considered, but have not been found persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
As set forth above, Song teaches various fusion proteins comprise a fragment of TSHR extracellular domain, a GS linker and a Fc, and methods of treating Graves’ disease by administering a pharmaceutical composition comprising the fusion protein. Saunders teaches the Fc variants comprising S267E mutation provide a range of effector function activities, such as enhanced CDC/decreased ADCC; or enhanced CDC/normal ADCC. Zocher teaches a design of Fc fusion protein with the potential to reduce antigen-specific antibody titers while, at the same time, depleting autoreactive B cells as the root cause of pathogenic autoantibodies. One of ordinary skill in the art would have had a reasonable expectation that the fusion protein with mutations comprising S267E, would have enhanced CDC activity, thus, enhanced activity to deplete specific B cells responsive for anti-TSHR autoantibody production. One of ordinary skill in the art would have had a reasonable expectation that the fusion protein with enhanced B-cell depletion activity would have enhanced therapeutic activity for treating Grave’s disease. The motivation would have been to expand options for Fc-fusion proteins with a range of effector functions and to develop a pharmaceutical composition with better therapeutic properties.
Applicant further argues unexpected results for the claimed compositions:
None of the cited art relates to the unexpected benefit the composition of claim 1 produces with respect to autoantibody clearance from circulation.
In fact, the S267E mutation greatly enhances autoantibody clearance from blood. More than just binding and neutralizing autoantibodies, by including the S267E mutation the molecule of the invention significantly enhances autoantibody clearance via enhanced binding to the CD32B. CD32B is expressed on liver sinusoidal endothelial cells, and these cells bind and internalize immune complexes thus removing them from blood. The inclusion of the S267E mutation in an antibody enhances binding to CD32B and thus enhances blood clearance.
The enhanced clearance of Graves' Disease autoantibodies by the composition of claim
1, is not merely the assertion of counsel. Applicant wishes to draw the Examiner's attention to paragraphs 5-9 of the inventor Dr. Kfir Oved's Declaration under 37 CFR 1.132 ("the
Declaration"). Paragraphs 5-9 describe an experiment performed by the inventors to compare the ability of molecules of claim I and molecules without the S267E mutation to clear autoantibodies. Molecules bearing three different TSHR fragments were tested. The first contained the 21-261 amino acid fragment of TSHR taught by Song and the instant application (CRD-1045). As can be seen in Figures XIA and XIB, the inclusion of the S267E mutation caused significantly more clearance of the M-22 autoantibody in comparison to WT IgG1 and thus significantly reduced TSHR stimulation. A fragment containing amino acids 21-280 bearing an E251K mutations and a fragment missing amino acids 317-366, which were both taught in the instant application, showed similar results. The inclusion of the S267E mutation caused significantly more autoantibody clearance and significantly reduced TSHR stimulation (Fig. X2
and X3).
Further, as shown in paragraph 10, the inclusion of the S267E mutation greatly enhanced binding of the TSHR-Fc fusions to B cells and decreased the CD32B detectable on the cells surface. This decrease in CD32B levels on the cell surface indicates increased binding of the receptor and increased internalization of the receptor complexed with the TSHR-Fc fusion.
The Office Action argues that a skilled artisan reading Zocher would be motivated to try and kill autoreactive B cells in Graves' disease as Zocher did in autoimmune encephalitis. The Office Action further argues that Saunders teaches that S267E enhances CDC and so a skilled artisan would be motivating to increase B cell killing as taught by Zocher by increasing CD with the mutation taught by Saunders. However, for CDC to occur the antibody must be present on the surface of the cell. The complement cascade must occur on the plasma membrane and then cell killing occurs by punching holes in that membrane. If the TSHR-Fc molecule is internalized into the B cells it cannot induce CDC. The Declaration shows that the S267E mutation greatly enhances B cell internalization of the TSHR-Fc molecule. This increase in internalization is the opposite of what a skilled artisan reading Zocher would want. Indeed, a skilled artisan reading of the many mutations of Saunders that can increase killing, would not select a mutation that also increases B cell internalization.
Applicant’s arguments and Kfir Oved’s Declaration under 37 CFR 1.132 have been fully considered, but have not been found persuasive. Applicant argues the unexpected results (e.g. enhanced CD32B) for a few fusion proteins disclosed in the specification. However, the activity is not unexpected. Sauders teaches that the S267E increased the affinity for increased biding to the inhibitory FcγRIIb (CD32B). Thus, enhanced binding to CD32B is expected. As set forth above, based on the teachings from Song, Zocher and Saunders one of ordinary skill in the art would have had a reasonable expectation of success and motivation to reach the claimed composition.
Additionally, the evidence of nonobviousness must be commensurate in scope with the claims to rebut the prima facie case of obviousness. See MPEP 716.02 (d). Thus the evidence provided in the specification and Declaration is not sufficient to overcome the obviousness rejection because the claims are not limited to fragments used in the Examples and Declaration. Thus, in view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Regarding the S267E mutation greatly enhances B cell internalization of the TSHR-Fc molecule as shown by the Declaration, one of ordinary skill would have considered all available evidence to make modification at Fc domain. Saunders clearly teaches that Ser267Glu (S267E) substitution in the IgG1 Fc region results in more potent Complement-Dependent Cytotoxicity (CDC). The largest improvement in CDC activity was achieved when S267E, H268F and S324T (termed the EFT mutations) were combined. Thus, the activity of improving CDC has been tested and proved for these mutations with multiple studies, as evidenced by Saunders. One of ordinary skilled in the art would not stop making such mutation because one negative result (in this case, unreported negative results). In addition, as shown by paragraph 10 of the Declaration, internalization occurs after binding of TSHR-Fc and CD32. Given that the Fc modification can increased C1q binding (page 8, col. 1, para. 2) and existed data in prior art, one of ordinary would have expected that the fusion protein comprising S267E mutation would bind C1q and initiate an enhance CDC before internalization.
Applicant further argues that one ordinary skilled in the art would not have a reasonable expectation of success:
In light of the increased B cell internalization produced by the S267E mutation a skilled artisan would not reasonably expect that combination with Zocher would produce increased B cell killing. Indeed, less B cell killing by CDC would be expected. In light of this, a skilled artisan would not expect the S267E mutation to increase killing and would not be motivated to combine it with Zocher. As such, instant claim 1 is nonobvious over the cited art.
Applicant’s arguments have been fully considered, but have not been found persuasive. As set forth above, given all the available evidenced in prior art, one of ordinary skill in the art would have a reasonable expectation of success that the mutation (S267E) would able to enhance CDC activity and improve the therapeutic activity of the fusion protein to autoimmune disease such as Graves’ disease.
Furthermore, in the field of biological technology, no invention has absolute certainty of success before experimental tests. Thus, only a reasonable expectation of success (not absolute) would have motivated an artisan to make the claimed fusion protein. Given the teachings from references, an ordinary skilled in the art would have would have had a reasonable expectation of success in producing the claimed invention.
Applicant further argues that the claimed composition has surprising superiority for treating Graves’ disease:
It is thus clear that the surprising superiority of an Fe bearing the S267E mutation for treating Graves' Disease could not have been predicted from the cited art. Indeed, the combination of art recited by the Office Action would not be expected to succeed in increasing B cell death by CDC. Further, the data provided clearly indicates that this surprising superiority is not dependent on the fragment used but is universal. As such, instant claim 1 is non-obvious over its entire scope.
However, these activities and/or properties are not recited by the claims; and the surprising superiority has not been shown to the broadly claimed genus of compositions. Based on the teachings from Song, Zocher and Saunders one of ordinary skill in the art would have had a reasonable expectation of success and motivation to reach the claimed composition.
Thus, the rejection is maintained for the reasons of record.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
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/CHENG LU/ Examiner, Art Unit 1642
/PETER J REDDIG/ Primary Examiner, Art Unit 1646