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 .
Application Status
2. Applicant’s amendment and response, submitted July 1, 2026, has been reviewed by the examiner and entered of record in the file. Claims 15-17, 19, and 21-30 are amended.
3. Claims 16, 17, 19, 22, 23 and 25-30 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected subject matter, without traverse, there being no allowable generic or linking claim.
4. As stated in the previous action, the scope of the independent invention that encompasses the elected species is as follows:
A method of increasing the activity, level, or any combination thereof of a mediator protein in a subject, wherein the mediator protein is selected from the list of mediator proteins in Table 3B, comprising administering amlexanox.
5. Claims 15, 21 and 24 are under examination with the elected species and are the subject of this office action.
Specification
6. The abstract of the disclosure was previously objected to. In view of Applicant’s submission of the replacement abstract on July 1, 2026, the previous objection is withdrawn.
Previous Claim Rejections - 35 USC § 112(b)
7. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
8. Claims 15, 21, and 24 remain 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.
9. Claim 15 remains rejected as being unclear for reciting the administration of a compound without specifying who or what is receiving the administration.
As amended, claim 15 recites: “… the method comprising administering a compound selected from…,” but fail to identify the subject/patient receiving the administration such that one skilled in the art would not know how to practice the claimed invention.
10. Applicant has amended the preamble to recite that the method of treatment is in a subject in need thereof, but has not clarified the step of administration, i.e., fails to recite an active step of administering a compound selected from the group recited in claim 15 to said subject.
In view of a broadest reasonable interpretation, claim 15 is construed to mean:
“A method of increasing the activity, level, or combination thereof of a mediator protein selected from … [language omitted], in a subject in need thereof,
comprising administering to said subject a compound selected from: metformin, pentosan polysulfate, amlexanox, leflunomide, prasterone, glutathione disulfide, pazopanib, bosutinib, dabrafenib, or baricitinib…” [emphasis added].
11. Claims 21 and 24 are rejected as being dependent upon and including all of the limitations of claim 15.
Previous Claim Rejections - 35 USC § 112(a)
12. Claims 15, 18 and 21 were previously rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement, regarding the full scope of compounds selected from metformin, pentosan polysulfate, amlexanox, leflunomide, prasterone, glutathione disulfide, pazopanib, bosutinib, dabrafenib, baricitinib, or a pharmaceutically acceptable salt, prodrug, or derivative thereof; or any combination thereof.
13. Applicant’s amendment to claim 15 limits the compound(s) to a compound selected from metformin, pentosan polysulfate, amlexanox, leflunomide, prasterone, glutathione disulfide, pazopanib, bosutinib, dabrafenib, or baricitinib.
14. Applicant demonstrates possession of the ten compounds embraced by the claims in Example 2, wherein the target gene of each “drug” (i.e., the ten recited compounds) is demonstrated (see Table 4, pages 62-63).
15. Accordingly, the previous written description rejection is withdrawn.
16. Claims 15, 21 and 24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of increasing the activity and/or expression level of certain mediator proteins in Tables 3B and 3D including PIGK, NRBP1, APOD, and LAMTOR2, comprising administering an effective amount of amlexanox (see Figure 7), does not reasonably provide enablement for a method of administering any amount of the full scope of compounds embraced by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
This rejection has been modified as necessitated by Applicant’s amendment to the claims.
17. The standard for determining whether the Specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? As recognized by the court in In re Wands, 858 F.2d 731 (Fed. Cir. 1988), that is still the standard to be applied, determined by consideration of the Wands factors (MPEP 2164.01(A)); namely, nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art, predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered, with the most relevant factors discussed below:
1) the quantity of experimentation necessary,
2) the amount of direction or guidance provided,
3) the presence or absence of working examples,
4) the nature of the invention,
5) the state of the prior art,
6) the relative skill of those in the art,
7) the predictability of the art, and
8) the breadth of the claims.
18. These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons.
19. Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.”
In the instant case, the claims are drawn to a method of increasing the activity, level, or any combination thereof of a mediator protein selected from the vast list of mediator proteins recited in claim 15 in a subject in need thereof,
the method comprising administering a compound selected from: metformin, pentosan polysulfate, amlexanox, leflunomide, prasterone, glutathione disulfide, pazopanib, bosutinib, dabrafenib, or baricitinib, wherein the subject has age-related large dendritic spine density loss.
20. The state of the prior art, level of predictability and relative skill level: As stated in MPEP 2164.05(a), “[t]he state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed.”
21. As discussed above, the instantly claimed invention pertains to a method of increasing the activity, level, or any combination thereof of a mediator protein selected from the vast list of mediator proteins in claim 15 in a subject, comprising administering a compound selected from: metformin, pentosan polysulfate, amlexanox, leflunomide, prasterone, glutathione disulfide, pazopanib, bosutinib, dabrafenib, or baricitinib, wherein the subject has age-related large dendritic spine density loss.
22. The relative skill of those in the art is high, that of an MD or PhD. That factor is outweighed, however, by the unpredictable nature of the art. The state of the art regarding the recited compounds, metformin is a known antidiabetic agent; pentosan polysulfate is known to treat intersitial cystitis; amlexanox is known for the treatment of canker sores and certain inflammatory conditions; leflunomide is known for treating rheumatoid arthritis; prasterone is known for treating menopause or adrenal insufficiency; glutathione disulfide is a known antioxidant; pazopanib, bosuitinib, dabrafenib, and baricitinib are known tyrosine kinase inhibitors that are useful for treating cancer and/or certain immune disorders.
23. As illustrative of the state of the art regarding age-associated dendritic spine loss, or age-related cognitive decline, Huang et al. teach that the effects of aging on cognitive decline and dendritic spine plasticity remain complicated and unclear:
“Despite many efforts, the cellular basis of age-related cognitive decline remains unclear. It was once believed that a generalized neuronal loss in the cerebral cortex and deterioration of dendritic branching occurs during normal aging and contributes to cognitive impairment (Brody, 1955; Coleman and Flood, 1987). Yet stereological studies have documented minimal aging-related neuronal loss in the cortex and hippocampus (West et al., 1994; Morrison and Hof, 1997)…
“Recent in vivo imaging studies reported that aging alters the dynamics of dendritic spines in the cortex of old mice (Mostany et al., 2013; Davidson et al., 2020). But how aging affects dendritic spine plasticity associated with learning remains unknown.” (Frontiers in Neural Circuits, 2020, page 1, last paragraph- page 2, second paragraph).
24. The amount of direction or guidance provided and the presence or absence of working examples: The amount of direction provided by the Applicant is considered to be determined by the Specification and the working examples. In the instant case, the specification provides no direction or guidance for the use of all of the compounds embraced by the claims for increasing the activity, level, or combination thereof of a mediator protein selected from the list recited in claim 15, in a subject in nee thereof, wherein said subject has age-related large dendritic spine density loss. In this case, the instant Specification discloses the effects of each recited compound on only one gene target each within said list of mediator proteins, and the use of only one of said compounds, i.e., amlexanox (Example 3 at pages 64-67).
25. No reasonably specific guidance is provided concerning useful therapeutic protocols comprising administering any other compound according to the instant claims.
26. The breadth of the claims: As stated in MPEP 2164.01(c), “[w]hen a compound or composition claim is limited by a particular use, enablement of that claim should be evaluated based on that limitation.” Thus, as stated in MPEP 2164.08, “[t]he focus of the examination inquiry is whether everything within the scope of the claim is enabled” (emphasis added). Indeed, the Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright, 999 F.2d 1557 (Fed. Cir. 1993) (emphasis added). At the same time, however, it is also recognized that not everything necessary to practice the invention need be disclosed. Nor is it necessary that an Applicant test all the embodiments of his invention. In re Angstadt, 537 F.2d 498 (CCPA 1976) (emphasis added). In fact, as stated by the court in In re Buchner, 929 F.2d 660 (Fed. Cir. 1991), a patent need not teach, and preferably omits, what is well known in the art.
27. Accordingly, for purposes of enablement, the relevant concern is whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate in scope with the protection sought by the claims. Thus, while “a patent application is entitled to claim his invention generically” it is necessary that “he provide a disclosure sufficient to enable one skilled in the art to carry out the invention commensurate with the scope of his claims." Amgen, Inc., v. Chugai Pharmaceutical Co., Ltd. (Fed. Cir. 1991). As noted by the court in In re Fisher, 427 F.2d 833 (CCPA 1970), the scope of enablement must bear a “reasonable correlation” to the scope of the claims. See also Ak Steel Corp. v. Sollac, 344 F.3d 1234 (Fed. Cir. 2003) and In re Moore, 439 F.2d 1232 (CCPA 1971). As stated in MPEP 2164.08, resolution of this concern requires two stages of inquiry: “[t]he first is to determine how broad the claim is with respect to the disclosure. The entire claim must be considered. The second inquiry is to determine if one skilled in the art is enabled to make and use the entire scope of the claim without undue experimentation”.
28. As to the first inquiry, as discussed above it is evident that the genus of compounds embraced by the claims has substantial variance, i.e., any compound selected from metformin, pentosan polysulfate, amlexanox, leflunomide, prasterone, glutathione disulfide, pazopanib, bosutinib, dabrafenib, or baricitinib, administered for increasing the activity, level, or combination thereof of a mediator protein selected from the extremely broad list recited in claim 15. Yet, as discussed above, the instant Specification discloses the effects of each recited compound on only one gene target each within said list of mediator proteins, and the use of use of only one of said compounds, i.e., amlexanox (Example 3 at pages 64-67).
As such, the claim is extremely broad with respect to the disclosure. The second inquiry is discussed in detail below.
29. The amount of experimentation necessary: In view of all of the foregoing, at the time the invention was made, it would have required undue experimentation to practice the entire scope of the invention as claimed. As discussed above, the claims are drawn to a method of increasing the activity, level, or any combination thereof of a mediator protein selected from the list of mediator proteins recited in claim 15 in a subject in need thereof, the method comprising administering a compound selected from: metformin, pentosan polysulfate, amlexanox, leflunomide, prasterone, glutathione disulfide, pazopanib, bosutinib, dabrafenib, or baricitinib, wherein the subject has age-related large dendritic spine density loss.
30. Since identifying any compound which is capable of successfully treating age-related dendritic spine density loss or cognitive decline is complex, the nature of the instant invention considered to be one of extreme complexity. In the instant case, this complexity is exacerbated by the broadness of the scope of claims 15, 21 and 24 with respect to the disclosure since the claims embrace administration of ten unrelated compounds, whereas the instant Specification discloses the administration of just one compound, exerting the desired activity on proteins of Tables 3B, and 3D (see Example 3 and Figure 7). Thus, it is highly unpredictable whether administering any compound embraced by the claims, based on the instant disclosure would, in fact, be usable. Whether the other compounds encompassed by the claims would be usable is even less predictable. As such, the only way to ascertain which of the claimed compounds presently embraced by the claims, other than amlexanox, are usable based on the limited disclosure would require undue experimentation. That is, the only way one skilled in the art is enabled to use the entire scope of the claim based on the instant disclosure entails undue experimentation.
31. To overcome this rejection, Applicant should narrow the scope of the claims such that they bear a reasonable correlation with the disclosure, i.e., limit the claims to the method disclosed in Example 3.
Response to Arguments
32. Applicant traverses the previous enablement rejection. Applicant argues that the amendment to the claims to remove the phrase: "a pharmaceutically acceptable salt, prodrug, or derivative thereof; or any combination thereof” as well as reciting the protein mediators overcome the scope of enablement rejection.
Applicant contends that as demonstrated in Example 2 of the Specification, the claimed drugs were identified using Signed Jaccard Score to quantitatively evaluate whether the net (direct and indirect) effects of each drug at all 203 mediator proteins opposes (i.e. is predicted to reverse) the effects of age on dendritic spines.
33. Applicant's arguments have been fully considered but they are not persuasive. While Applicant’s amendments narrow the scope of recited compounds to metformin, pentosan polysulfate, amlexanox, leflunomide, prasterone, glutathione disulfide, pazopanib, bosutinib, dabrafenib, or baricitinib, said compounds have demonstrated the direct or indirect effects on just one gene target each within the 203 mediator proteins identified in Example 1, (see Table 4 of Example 2) for reversing the protein mediator signature of age-dependent dendritic spine loss. That is, the Specification identifies just one gene target per compound embraced by the claims as shown in Table 4:
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, (specifically, GDP1, FGG1, PTK2B, GRIN1, MGST1, CAMK2G, or LIMK1), and does not provide support for increasing the activity, level, or combination thereof of the full scope of mediator proteins recited by the claims, in a subject in need thereof, comprising administering any of said compound(s) to said subject, wherein said subject has age-related large dendritic spine density loss.
Accordingly, the previous enablement rejection is maintained.
Previous Claim Rejections - 35 USC § 103
34. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
35. Claims 15, 18, 21 and 24 were previously rejected under 35 U.S.C. 103 as being unpatentable over Xu et al., Chemistry Open (2021), as evidenced by Querfurth and LaFerla, N Engl J Med (2010), and further in view of Xia et al., Frontiers in Immunology (2018).
36. In view of Applicant’s amendments to the claims, the previous rejection has been modified and newly applied as follows:
37. Claims 15, 21 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al., Chemistry Open (2021), in view of Boros et al., Ann Neurol 2017, cited on Applicant’s IDS of October 1, 2024), and in view of Liu et al., WO2018204764 A1.
Claim 15, as amended, is drawn to a method of increasing the activity, level, or any combination thereof of a mediator protein selected from ACSS3, PCBD1, RAB9A, SCG2, RAB9B, CNN3, CAPG, SLC25A1, PPP1R1B, UBE2I, SLC7A5, MGST1, PSME2, RSU1, BLVRB, DNAJC19, ARMC10, CYB5R3, CLPB, TPM1, SERINC1, RAB23, XKR4, CPLX3, CYP46A1, CXADR, PURG, CAMK4, CBARP, PIANP, ADGRB2, CRIP2, NTNG2, CA11, MAL2, KIF16B, RASAL1, TTPAL, PLCH2, KALRN, CACNG3, LASP1, BAIA P2, AP1S1, BSN, HMGCS1, LRRC73, ATP5MD, ARPC5L, ATG101, PDZD4, CASK, CELF5, SYT5, RGS17, SMIM13, TRIO, CSDC2, CRMP1, SNCA, STK32C, ZNF706, ARL10, SYNGR1, MTPN, KIF3A, GRIN1, CDK16, STMN1, MAPT, CAPN5, SLC4A10, TMEM163, DGKB, REPS1, ARPP19, CAMKV, CCDC124, SLC17A7, DOC2A, DMTN, DLGAP1, EEF1E1, RAD23B, CHM, FRRS1L, ENSA, TMEM63B, UBE3A, ABRAXAS2, MAPK10, SYN2, REEP1, PAK3, EIF3I, RTN1, STX12, SYN1, RPL13, RPS9, QARS1, PLD3, LMBRD2, RPL7, SLC30A1, SCN2A, TSPAN7, PPM1H, PSMD1, EXOC4, and PSMC2, in a subject in need thereof, (more specifically, a protein of Table 3B),
the method comprising administering a compound selected from: metformin, pentosan polysulfate, amlexanox, leflunomide, prasterone, glutathione disulfide, pazopanib, bosutinib, dabrafenib, or baricitinib (more specifically, amlexanox (claims 21 and 24)),
wherein the subject has age-related large dendritic spine density loss.
In view of a broadest reasonable interpretation, claim 15 is construed to mean:
“A method of increasing the activity, level, or combination thereof of a mediator protein selected from [language omitted], in a subject in need thereof,
comprising administering to said subject a compound selected from: metformin, pentosan polysulfate, amlexanox, leflunomide, prasterone, glutathione disulfide, pazopanib, bosutinib, dabrafenib, or baricitinib, and
wherein the subject has age-related large dendritic spine density loss.
38. Xu et al. teach the critical role of up-regulated glutaminyl cyclase (QC) in the pathology of Alzheimer’s disease (AD) and go on to teach that teach that “QC, distributed mainly in brain, is thus regarded as a critical target to prevent and treat AD,” (see abstract and page 878, right column, last paragraph). Xu et al. suggest the administration of known QC inhibitors as a therapeutic strategy for improving cognitive deficits in a murine model of AD:
“a number of QC inhibitors have been reported, which improve behavioral and cognitive deficits in AD mice by inhibiting QC activity.”
(page 878, left column, first paragraph). In Table 1, Xu et al. specifically name Amlexanox as one of five “[t]op FDA-approved drugs exhibiting QC inhibitory activities” (page 878, see Table 1 and).
39. Boros et al. teach that Alzheimer’s disease (AD) is characterized by reduced dendritic spine density, and that age is inversely proportional to spine density:
“Spine density, measured per dendrite length or dendrite surface area, was similar among control and CAD cases but reduced in AD (Fig. 2, A–D and Supplementary Tables 1–2) … [language omitted] collective analysis of all cases revealed that age was inversely proportional to spine density,”
(see page 6 under “Results”). Boros et al. go on to teach that the number of mushroom spines were reduced significantly in AD compared to control (page 7, first paragraph), and define mushroom spines as having head diameter greater than 0.35 mM and a length of at least 0.875 mM (i.e., mushroom spines have a length-to-head ratio of 2.5) (page 5, first full paragraph), which meets the definition of large as set forth by Applicant (i.e., >0.90 mM3) at page 3, second to past paragraph.
40. As such, one of skill in the art before the effective filing date of the claimed invention have been motivated to treat an aged subject with Alzheimer’s disease comprising administering the QC inhibitor amlexanox to said subject, and would reasonably expect that said subject would have large dendritic spine density loss, with a reasonable expectation of success.
41. Xu et al. do not teach the mechanism of increasing the activity of a mediator protein recited by claim 15.
42. Yet, Liu et al. teach the targeted modulation and/or optimization of gene expression comprising administering a stimulus that perturbs a genomic signaling center (GSC), wherein the stimulus is a small molecule, and specifically names amlexanox (paragraphs [0136], and [0145]), and wherein said targeted modulation is associated with at least one gene in Tables 1-9 for the treatment of Alzheimer’s disease, (paragraph [0190]). Liu et al. disclose at least the recited genes PCBD1, SCG2, RSU1, BLVRB, PPP1R1B (paragraph [0540]), UBE2I (paragraph [0541]), RAB9A (paragraph [0539]), RAB9B (paragraph [0435]), and CNN3, CAPG, SLC25A1, MGST1, and PSME2 (Table 68), for example.
43. Therefore, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention that when administered to a subject with Alzheimer’s disease and associated large dendritic spine density loss, amlexanox would necessarily target the above-named genes in the subject, as specifically recited by claim 15. Regarding the comprehensiveness of the genes listed in the Tables disclosed by Liu et al., as well as the small molecules that are stimulus for perturbing a GSC, in this case, when the species is clearly named, the species claim is anticipated no matter how many other species are additionally named. Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter.1990) (The claimed compound was named in a reference which also disclosed 45 other compounds. The Board held that the comprehensiveness of the listing did not negate the fact that the compound claimed was specifically taught. The Board compared the facts to the situation in which the compound was found in the Merck Index, saying that "the tenth edition of the Merck Index lists ten thousand compounds. In our view, each and every one of those compounds is described' as that term is used in 35 U.S.C. § 102(a), in that publication."). Id. at 1718. See also In re Sivaramakrishnan, 673 F.2d 1383, 213 USPQ 441 (CCPA 1982).
Thus, one of skill in the art before the effective filing date of the claimed invention would have been motivated to administer amlexanox to a patient suffering from AD and dendric spine density loss, wherein said administration would have resulted in an increase in the above-named genes, with a reasonable expectation of success.
44. And, the fact that applicant 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. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
As such, claims 15, 21 and 24 are prima facie obvious.
Response to Arguments
45. Applicant traverses the obviousness rejection, arguing that Xu silent with regards to amlexanox increasing the activity, level, or any combination thereof of a mediator protein, as claimed, in a subject in need thereof where the subject that has age-related large dendritic spine density loss.
Applicant argues that Querfurth nor Xia, alone or in combination, cure the deficiencies of Xu, at least because neither Querfurth nor Xia disclose or suggest a method of increasing the activity, level, or any combination thereof of a mediator protein claimed in a subject that has age-related large dendritic spine density loss. Accordingly, the Office has failed to establish a prima facie case of obviousness.
Applicant alleges that nothing in Xu, Querfurth, or Xia would have suggested to one of ordinary skill in the art that administration of the claimed compounds would increase the activity, level, or any combination thereof of a mediator protein, as claimed, in a subject that has age-related large dendritic spine density loss.
46. Applicant's arguments have been fully considered but they are not persuasive. Applicant’s arguments have been considered but are moot because the new ground of rejection does not rely on the Querfurth or Xia references applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. In this case, Xu is relied upon for suggesting the administration of QC inhibitors for treating Alzheimer’s disease, and naming amelexanox as the QC inhibitor.
Boros et al. teach that Alzheimer’s disease (AD) is characterized by reduced dendritic spine density, as is advanced age. And Liu et al. suggest the modulation of gene expression comprising administering a small molecule stimulus that perturbs the GSC, wherein the gene is selected from at least a dozen or more of Applicant’s instantly recited genes, and said modulation treats Alzheimer’s disease.
As such, claims 15, 21 and 24 are prima facie obvious.
Conclusion
47. Claims 15, 16, 17, 19 and 21-30 are present in the application, and claims 16, 17, 19, 22, 23 and 25-30 are withdrawn from consideration. Claims 15, 21 and 24 are rejected. No claim is presently allowed.
48. 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.
49. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached Monday-Friday 8:30AM-5PM EST.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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