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 . 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.
Priority
The instant application is a 371 of PCT/US21/12412 filed on 01/07/2021, which claims domestic benefit to US provisional application no. 62/958,328 filed on 01/08/2020.
Status of the Claims
The claim amendments and remarks filed on 11/16/2025 are acknowledged. Claims 1, 16, 22, 24, and 30-31 are amended. Claims 7, 15, 17-21, 23, 25-29, and 32-37 are cancelled.
Accordingly, claims 1-6, 8-14, 16, 22, 24, and 30-31 are pending and being examined on the merits herein.
Withdrawn Objections/Rejections
The objections to the drawings in view of the newly filed drawings on 11/16/2025 which now have sufficient resolution and legibility for FIG. 1 and 7B.
The objections to claims 1, 7, 15, 22, 24, and 30-31 are withdrawn in view of the suggestions being incorporated into the amendments.
The 35 USC 102 rejections over Brachwitz for claims 1-3, 5, and 7 and over Nyce for claims 1-3, 5, 7-8, 11, and 30-31 are withdrawn in view of claim 7 being cancelled, and claim 1 has been amended to require a complex comprising of a compound having “12 to 24 carbon atoms” as well as further including a recited “nucleic acid molecule”, wherein “the compound non-covalently complexes to the nucleic acid molecule”, which has changed the scope of the claims.
The 35 USC 103 rejections over Nyce for claims 1-11, 15-16, 22, 24, and 30-31, over Nyce in view of Kuijpers for claims 12-14 are withdrawn in view of claims 7 and 15 being cancelled, and claim 1 has been amended to require a complex comprising of a compound having “12 to 24 carbon atoms” as well as further including a recited “nucleic acid molecule”, wherein “the compound non-covalently complexes to the nucleic acid molecule”, which has changed the scope of the claims.
The following grounds of rejections are new as necessitated by Applicant’s amendments.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 8 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 8 recites “The compound of claim 7 … “.
Claim 8 is indefinite because claim 8 depends upon cancelled claim 7, making the metes and bounds of the claim unclear.
For purposes of examination, claim 8 is being interpreted as the complex of instant claim 1, wherein the compound comprises two alkyl groups each having about 12 to about 24 carbon atoms.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-6 and 9-14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The preamble of claims 2 and 9-12 recite “The compound of claim 1 …”, the preamble of claims 3 and 5 recite “The compound of claim 2 …”, the preamble of claim 4 recites “The compound of claim 3 …”, the preamble of claim 6 recites “The compound of claim 5 …”, the preamble of claim 13 recites “The compound of claim 12 …”, and the preamble of claim 14 recites “The compound of claim 13 …”.
There is insufficient antecedent basis for “The compound” limitation in instant claims 2-6 and 9-14 because it is unclear if the preamble recitation of “The compound” is referring back to the compound that is in the complex of instant claim 1.
For purposes of examination, instant claims 2-6 and 9-14 are being interpreted such that the preamble recitation of “The compound” is referring to the compound in the complex of instant claim 1.
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.
Claim(s) 1-3, 5, 8, 10-11, 16, 22, 24, and 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Nyce et al. (CA2304312A1 in PTO-892 dated 05/15/2025) and as evidenced by ChEBI in PTO-892 dated 05/15/2025 (CDP diacylglycerol compound information and structure).
Nyce et al. discloses agents, comprising an anti-sense oligonucleotide hybridizing to two or more mRNAs, or multiple target anti-sense oligos (MTA oligos) (see page 3, lines 19-25). Nyce et al. discloses that their agents encompass oligonucleotides which are anti-sense to naturally occurring DNA and/or RNA sequences (see page 18 lines 4-32). Nyce et al. discloses that their oligonucleotides comprise of various sequences of nucleotides including adenosine, cytidine, thymidine, and guanosine (see page 8 lines 48-55).
Nyce et al. further discloses that their compositions can include one or more surfactants that is suitable for enhancing the uptake of the anti-sense oligonucleotides (see page 79, lines 27-30). Nyce et al. discloses several surfactants that can be used for their composition such as cytidine diphosphate (CDP) diacylglycerol and among others (see page 80, lines 1-2). As evidenced by ChEBI, CDP diacylglycerol consists of a cytidine diphosphate group that is covalently linked to two fatty acids with alkyl chain lengths of 12 and 14 carbon atoms and has a net charge of 0 (see pages 2 and 4 in ChEBI). Nyce et al. discloses that surfactants may be used either as a surfactant in a formulation, or as a covalent bound addition to the 5’ and/or 3’ ends of the anti-sense oligonucleotides (see page 80 lines 9-11).
Nyce et al. discloses that the agents are also provided as a pharmaceutical composition and includes suitable pharmaceutically acceptable carriers such as sterile 45 pyrogen-free saline solution (see page 77, lines 40-45). Nyce et al. discloses that the anti-sense oligonucleotide may also be contained in a pharmaceutical formulation within a lipid particle or vesicle such as a liposome or microcrystal (see page 78, lines 11-14). Nyce discloses that these lipid compositions can be unilamellar or plurilamellar and include positively charged lipids such as DOTAP (see page 78 lines 11-20). Nyce et al. discloses that their compositions may be administered in a respiratory system as an aerosol formulation including particles of respirable size sufficiently small to pass through the nose, mouth, and larynx upon inhalation and through the bronchi and alveoli of the lungs. Nyce et al. discloses that the respirable particles range from about 0.5 to 10 microns in size (see page 81, lines 29-36). Here, the respiratory formulation disclosed in Nyce et al. is being interpreted as a microdroplet since the aerosol particles are of micron size.
Nyce et al. discloses that their compositions may be applied for the treatment of a disease or condition associated with the presence of an mRNA corresponding to at least one target gene, genomic flanking regions or proteins, by administration to a subject an amount of the MTA oligo to reduce the production or availability of at least one of the target mRNAs (see page 4 lines 3-8).
The difference between Nyce and the claimed invention is that Nyce does not exemplify a complex comprising the compound of instant claim 1 and a recited nucleic acid, wherein the compound of instant claim 1 is non-covalently complexed to the nucleic acid molecule.
It would have been prima facie obvious before the effective filing date to include CDP diacylglycerol as the surfactant in a formulation comprising the anti-sense oligonucleotides disclosed in Nyce et al. to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Nyce et al. provides guidance that surfactants can be used as a part of a formulation and further discloses that CDP diacylglycerol is suitable for use as a formulation surfactant to enhance the uptake of the anti-sense oligonucleotides.
In regards to instant claim 22, it would have also been prima facie obvious before the effective filing date of the claimed invention to have prepared the formulation of Nyce as described above within a liposome as disclosed in Nyce. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Nyce provides guidance the anti-sense oligonucleotide may also be contained in a pharmaceutical formulation within a lipid particle or vesicle such as a liposome.
In regards to instant claim 24, it would have also been prima facie obvious before the effective filing date of the claimed invention to have prepared the formulation of Nyce as described above as a microdroplet as disclosed in Nyce. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Nyce provides guidance that their compositions can be formulated into aerosol particles that are in the micron range.
In regards to instant claim 30, it would have also been prima facie obvious before the effective filing date of the claimed invention to have prepared the formulation of Nyce as a pharmaceutical composition further comprising pharmaceutically acceptable carriers such as sterile 45 pyrogen-free saline solution as disclosed in Nyce. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Nyce provides guidance that their compositions are pharmaceutical compositions and can include suitable pharmaceutically acceptable carriers such as sterile 45 pyrogen-free saline solution.
In regards to instant claim 31, it would have also been prima facie obvious before the effective filing date of the claimed invention to have administered the formulation of Nyce as described above for the treatment of a disease or condition associated with the presence of an mRNA corresponding to at least one target gene, genomic flanking regions or proteins as disclosed in Nyce. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Nyce provides guidance that their compositions may be applied for the treatment of a disease or condition associated with the presence of an mRNA corresponding to at least one target gene, genomic flanking regions or proteins, by administration to a subject an amount of the MTA oligo to reduce the production or availability of at least one of the target mRNAs.
Claim(s) 4, 6, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Nyce et al. (CA2304312A1 in PTO-892 dated 05/15/2025) and as evidenced by ChEBI in PTO-892 dated 05/15/2025 (CDP diacylglycerol compound information and structure), as applied to claims 1-3 and 5 above, and further in view of Simeone et al. (European Journal of Medicinal Chemistry, 2012 in PTO-892).
The teachings of Nyce and evidence of ChEBI are as described above and teach the complex of claims 1-3 and 5 as discussed above.
The difference between Nyce and the claimed invention is that Nyce does not teach two or more of the recited moieties for the one or more nucleosides as well as the one or more nucleoside comprise deoxyribonucleic acids.
Simeone discloses the synthesis, self-aggregation, and bioactivity properties of highly functionalized nucleolipids (see Abstract).
Simeone discloses that the features of nucleolipids, associating the ability of nucleosides to specifically recognize complementary bases via Watson-Crick or Hoogsteen H-bonds with the strong tendency of lipids to spontaneously self-assemble in aqueous solutions, have attracted wide interest in several fields, have attracted wide interest in several fields, with major impact on biotechnological and pharmacological applications (first paragraph left column page 429). Simeone discloses that nucleolipids are nucleosides decorated with a polar group - either charged or not - attached at the 5’ position of the ribosidic moiety, and lipophilic chains at the 2’ and/or 3’-OH groups, assembled in a molecular skeleton resembling naturally occurring glycerophospholipids, the main constituents of cell membranes, and that these nucleolipid-based aggregates may may typically be exploited as drug-carriers, being able to incorporate bioactive compounds in high concentration, protecting them against extra cellular enzymatic degradation and allowing efficient delivery within cells by endocytosis (first and second paragraph left column page 429). Simeone discloses that cationic nucleolipids have attracted interest due to their intrinsic molecular recognition and cell penetrating abilities (see last paragraph right column page 429), and therefore Simeone discloses a novel synthetic platform of functional nucleolipids with a higher degree of functionalization than generally allowed starting from natural ribo- or deoxyribonucleosides (see second paragraph left column page 43).
Simeone demonstrates the synthesis steps of their nucleolipids in Scheme 2 (page 432), where a modified 3’-azido-3’-deoxy-1-b-D-xylofuranosyluracil from Scheme 1 (page 431) is further functionalized with various substituents as shown below:
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Here, the compounds of Simeone meet the limitation of the recited compound because the compound of Simeone contains a deoxy-uracil/uradine nucleoside and a 17 carbon alkyl chain at the 2’ position.
Simeone demonstrates in Fig. 4 and 5 as well as Table 1 on page 433 that this nucleolipid behaves as a weakly charged cationic surfactant, and further demonstrates in Table 2 and Fig.6 on page 434 that this nucleolipid is endowed with a not negligible bioactivity, more marked against human cancer cells MCF-7 and WiDr (see first paragraph left column page 435). Simeone concludes that their results demonstrate that a tailored design of nucleolipid-based systems can be profitably exploited to
obtain cationic surfactants with acceptable biocompatibility, and that high versatility of their presented synthetic strategy allows to prepare a large variety of diverse nucleolipid analogs, having distinctive features which can be finely modulated by proper choice of the ribose decorations (see second paragraph left column page 435).
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the liposome composition of Nyce as described above by further including the nucleolipids disclosed in Simeone to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to make this modification because Simeone discloses that their nucleolipids not only function as a surfactant but also has bioactivity on tumoral cell lines. One of ordinary skill in the art would have a reasonable expectation of success because Nyce discloses that their lipid formulations can include various surfactants to enhance uptake the of the anti-sense oligonucleotides, and Simeone also discloses that their nucleolipid behave as surfactants and further suggests its use as a carrier for bioactive compounds.
Claim(s) 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Nyce et al. (CA2304312A1 in PTO-892 dated 05/15/2025) and as evidenced by ChEBI in PTO-892 dated 05/15/2025 (CDP diacylglycerol compound information and structure), as applied to claim 1, and further in view of Kuijpers et al. (Bioconjugate Chem, 1993 in PTO-892 dated 05/15/2025).
The teachings of Nyce et al. and evidence of ChEBI are as described above. Furthermore, Nyce et al. discloses that their agent may be suitable for administration before, during, and after other treatments, including radiation, chemotherapy, antibody therapy, phototherapy and cancer, and other types of surgery. Nyce et al. discloses their agent may be effectively administered in conjunction with other therapies. (see page 4, lines 21-26).
The difference between Nyce et al. and the claimed invention is that Nyce et al. does not expressly teach a compound that further comprises a targeting ligand such as an antibody.
Kuijpers et al. discloses administration of an antibody-DNA conjugate, followed by targeting with radiolabeled complementary DNA (antisense DNA) in a two-step radioimmunotherapy of cancer (see Abstract). Kuijpers et al. illustrates the principle of the antibody-DNA conjugate targeting mechanism (see Scheme I on page 95). Kuijpers et al. discloses that in radioimmunotherapy, a high radiation dose is required in order to kill the tumor cells which results in serious radiation damage to healthy tissue (see page 94, left column). Kuijpers et al. discloses that due to this poor tumor to normal tissue ratio, the application of radiolabeled antibodies in cancer therapy have been limited to tumors which can be treated by intracavitary administration (see page 94, left column). Kuijpers et al. further discloses that in order circumvent this limitation, a pretargeting strategy approach is used by prelocalizing antibody-DNA conjugates that target the antigen sites on tumor cells as well as having specificity for a radioactive ligand such as the radiolabeled antisense DNA. Once the optimal tumor to normal tissue uptake of the antibody is reached, the radiolabeled antisense oligonucleotide is subsequently administered (see page 94, left column and Scheme I on page 95). Kuijpers et al. discloses the preparation of the antibody-oligonucleotide conjugate (see Scheme III on page 99).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention by conjugating an antibody as disclosed in Kuijpers to the ASO in the composition of Nyce as described above to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Nyce et al. provides guidance that their oligonucleotides agents can be effectively co-administered with other therapies such as radiation and antibody therapy, and Kuijpers et al. provides guidance of antibody-oligonucleotide conjugates that can be used for radioimmunotherapy to enhance the uptake of radiolabeled antisense oligonucleotide agents for killing the tumor cells and reducing damage to normal cells.
Claim(s) 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Nyce et al. (CA2304312A1 in PTO-892 dated 05/15/2025) and as evidenced by ChEBI in PTO-892 dated 05/15/2025 (CDP diacylglycerol compound information and structure), as applied to claim 1, and further in view of Meissner et al. (Journal of Controlled Release, 2015 in PTO-892)
The teachings of Nyce et al. and evidence of ChEBI are as described above. Furthermore, Nyce et al. discloses that their agent may be suitable for administration before, during, and after other treatments, including radiation, chemotherapy, antibody therapy, phototherapy and cancer, and other types of surgery. Nyce et al. discloses their agent may be effectively administered in conjunction with other therapies. Nyce discloses exemplary diseases and conditions including cancers such leukemias and among others (see page 4, lines 21-26).
The difference between Nyce et al. and the claimed invention is that Nyce et al. does not teach a complex that further comprises a targeting ligand such as an antibody.
Meissner discloses therapeutic liposome formulations characterized by high transfection efficiency, stability in the presence of serum, as well as specificity and toxicity for target (leukemic) cells (see Abstract). Meissner discloses that their liposome formulations consist of a core composed of antisense oligonucleotides complexed by either cationic lipid, DOTAP, or a synthetic polycation, polyethyleneimine, encapsulated within liposomes modified with polyethylenoglycol (see Abstract).
Meissner discloses that targeted vectors are increasingly favored tools for specific delivery
of antisense oligonucleotide-based therapeutics into cancer cells (see second paragraph left column page 516). Meissner discloses that the liposomal shells are also enriched with covalently-bound antibodies recognizing a well characterized bio-marker, CD20, exposed on the surface of leukemia cells (see Abstract and Fig. 1). Meissner discloses that their immunoliposomes selectively and effectively reduced the expression of BCL2 in target cells (see Abstract). Meissner demonstrates in Fig. 7 that their liposome formulations showed high efficiency against specific tumor development in model mice-engrafted tumor experiments.
Meissner also discloses that antisense nucleotides, in particular those containing CpG islands can induce inflammatory and immunological response in patients' cells (see first paragraph under section 3.2.6 on page 521-522). Meissner demonstrates in Fig. 5 that their lipid formulations exhibited low immunostimulatory effects compared to free antisense oligonucleotides.
Meissner concludes that their lipid formulations that are additionally equipped with antibodies are promising non-viral vectors for specific oligonucleotide transfer into human tumor cells (see Abstract), and that these lipid formulations show high therapeutic efficacy with only a limited immunostimulatory effect that antisense oligonucleotides have traditionally suffered from (see second paragraph under section 5. Conclusions on page 526).
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the liposome composition of Nyce as described above by further conjugating antibodies to the liposome as disclosed in Meissner to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to make this modification because Meissner that lipid-antisense oligonucleotide formulations that are additionally equipped with antibodies have high therapeutic efficacy with only a limited immunostimulatory effect that antisense oligonucleotides have traditionally suffered from. One of ordinary skill in the art would have a reasonable expectation of success because Nyce et al. provides guidance that their compositions can be formulated within liposomes, and further discloses that their compositions can be used for the treatment of various cancers including leukemia.
Response to Arguments
Applicant’s arguments filed on 11/16/2025 have been fully considered in so far as they apply to the rejections of the instant office action, but were not persuasive.
Applicant states that Nyce discloses a composition of an ASO hybridized to mRNAs, in which one or more surfactants may be present such as CDP-DG. Applicant states that the CDP-DG of Nyce serves as a surfactant, and that there is no disclosure or evidence of any kind that the CDP-DG forms a complex with ASO or mRNA.
Applicant’s argument described above was not persuasive because even though Nyce does not explicitly disclose that the CDP-DG surfactant will form a complex with their ASO, Nyce does teach that the surfactant enhances uptake of the ASOs as described above, and the complex would flow naturally from following the suggestions of Nyce when the CDP-DG is added into their formulations.
MPEP 2145 II recites “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter.m 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed that an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) ("The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.").”
Applicant states that Kuijper does not cure the deficiencies of Nyce because Kuijper does not teach or suggest a non-covalent complex of the recited compound and a recited nucleic acid molecule. Applicant states that the mere fact that references can be combined or modified does not render the resultant combination obvious unless the results would have been predictable, and that there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.
Applicant’s argument described above was not persuasive because the teachings of Nyce establishes obviousness to arrive at the recited non-covalent complex as described above. Furthermore, an ordinary skilled artisan would have found it obvious to further conjugate an antibody to the ASO disclosed in Nyce with a reasonable expectation of success because Nyce et al. provides guidance that their oligonucleotides agents can be effectively co-administered with other therapies such as radiation and antibody therapy, and Kuijpers et al. provides guidance of antibody-oligonucleotide conjugates that can be used for radioimmunotherapy to enhance the uptake of radiolabeled antisense oligonucleotide agents for killing the tumor cells and reducing damage to normal cells.
Lastly, it is noted that instant claim 12 only requires “further comprising a targeting ligand”, and does not specify or limit where the targeting ligand is conjugated within the complex that comprises the recited compound and nucleic acid molecule. Therefore, both the previous rejection over Nyce in view of Kuipers as well as new rejection over Nyce in view of Meissner, which establish obviousness to either conjugate the targeting ligand to the ASO (Nyce in view of Kuijpers) or to the lipid complex (Nyce in view of Meissner), meet the limitation of the claim.
Conclusion
No claim is found allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/D.H.C./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693