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 .
The Applicants’ Amendment to the Claims filed on 12/01/2025 is entered.
Election/Restrictions
Applicant's election with traverse of invention Group I (e.g., present claims 1-8 and 11-14) and of the species: A: claim 2; B & D: SEQ ID NO: 2; C: viral infections, in the reply filed on April 28, 2025 is as previously acknowledged.
Claims 15-19, 21, and 23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention Group, there being no allowable generic or linking claim.
Claims 3, 11-12 and 13-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claim status
Claims 5, 7, 9-10, 20, 22, and 24 are canceled.
Claims 1-4, 6, 8, 11-19, 21, and 23 are pending.
Claims 15-19, 21, and 23 are withdrawn to non-elected invention Group.
Claims 3, and 11-14 are withdrawn to non-elected species claims.
Claims 1-2, 4, 6, and 8 are under examination.
This is the First Office Action on the Merits of US 18/479,600 filed on 10/02/2023 which is a DIV of 16/622,469 filed on 12/13/2019 (US Patent 11,771,739)
which is a 371 of PCT/US2018/037993 filed on 06/18/2018 which claims US priority benefit of US Provisional 62/521,159 filed on 06/16/2017.
Priority
This US 18/479,600 filed on 10/02/2023 which is a DIV of 16/622,469 filed on 12/13/2019 (now US Patent 11,771,739) which is a 371 of PCT/US2018/037993 filed on 06/18/2018 claims US Priority benefit of US Provisional 62/521,159 filed on 06/16/2017. The Filing Receipt filed on 05/21/2024 is controlling. As noted in the previous office action, the disclosure of the prior-filed application, US Provisional 62/521,159 provides no support for “subacute inflammation” and “chronic inflammation” of claim 4. The ‘159 provides no support for the inflammation localized to the heart, brain, etc., of claim 6. The ‘159 Provisional provides no support for SEQ ID NOs: 6-9 and 16, of presently amended claim 1). The ‘159 Provisional provides no support for viruses listed in claim 8, such as Coronavirus. Thus, claims 1-2, 4, 6, and 8 do not receive an effective filing date to the ‘159 Provisional filing date of 06/16/2017.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Written Description
Currently amended claims 1-2, 4, 6, and 8 stand 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the full-scope of the claimed invention.
Claims are drawn to a method of treating microbial inflammation caused by a viral infection in a subject by administering a therapeutically effective amount of an antimicrobial agent and a composition comprising a Nuclear Transport Modifier (NTM), the NTM comprising the sequence of the elected species of SEQ ID NO:2. The claims include chronic inflammation and sepsis, etc. (See claim 4). The claims include microbial inflammation localized to the blood, brain, etc. (See claim 6). The claims include inflammation caused by a viral infection including HSV-1, HSV-2, Coronavirus, and HIV type-1, etc. (See claim 8). Thus the claims require a critically essential element of combination of an antimicrobial agent and a composition comprising a Nuclear Transport Modifier comprising the sequence of instant SEQ ID NO: 2 which can treat such microbial inflammation.
MPEP § 2168 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Scope of the claims: The claims are broad to treating any inflammatory disorder caused by a viral infection in a subject comprising administering to the subject a therapeutically effective amount of any antimicrobial agent and a composition comprising a Nuclear Transport Modifier comprising the sequence of instant SEQ ID NO:2 (elected species). Regarding NTM, Applicant’s specification informs that the phrase “nuclear transport modifier” means peptide that is capable of modulating entry of transcription factors into the nucleus. An example of a nuclear transport modifier is a 26-29 amino acid peptide derived from human nuclear factor kappa B1 nuclear localization sequence and from human Fibroblast Growth Factor 4 signal sequence hydrophobic region. This phrase is used interchangeably with the phrase “nuclear import inhibitor.”
Although currently amended claim 1 recites SEQ ID NO: 2, claim 1 is still broad to the element of anti-microbial agent. Specifically, note that claim 8 recites many types of viruses. An anti-microbial agent is broad to a specific antiviral required for the many virus types listed in claim 8.
The state of the art shown in the prior art reference US2013/0089528 (of record) which discloses administering the peptide comprising instant SEQ ID NO: 2 to a subject to treat inflammation caused by diabetes including microbial-related diabetes. (See attached STIC SEQ ID NO results). However, this reference is silent regarding combining this treating with an anti-microbial.
Actual Reduction to Practice: MPEP § 2168 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. In the instant case, Applicants reduce to practice the NTMs recited in claim 1 for treating a microbial inflammation. Also, Applicants list many types of anti-microbial agents in page 22, para bridging pages 22-23. However, the specification does not show a representative set of treatments for treating specific viral infections using a combination of peptides listed in claim 1 and a specific antiviral. As discussed above the claim scope is potentially enormous; in comparison, the scope of the description which only has cSN50.1 reduced to practice, is extremely narrow. One of ordinary skill in the art would not consider the Examples in the instant specification to be representative of the full scope of the claimed genus. Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic: MPEP § 2168 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination thereof. The specification shows several species of N50 NTM (see Table). Although one of ordinary skill in the art could determine if a given amino acid sequence meets the structural requirements of the genus combined with a specific anti-microbial, it would not be possible to determine from the sequence alone if the anti-microbial-peptide combination was able to treat the breadth of the disorders found in instant claims.
Physical and/or chemical properties: In the instant case, Applicants are claiming a function of treating microbial inflammation caused by a viral infection in a subject without ample structure of the combination of anti-microbial agent and instant SEQ ID NO:2.
Functional characteristics when coupled with a known or disclosed correlation between function and structure: The specification does not describe a general correlation between structure and function for the claimed genus of anti-microbial agent. The role of the individual amino acids of N50 combined with any anti-microbial agent in treating the claimed disorders is not described. As a result, it is impossible to predict, based on the specification, how changing any structure of the combination will affect the ability of the compound to modulate nuclear transport and treat the inflammatory conditions.
Method of Making: Solid state peptide synthesis and cloning, recombinant expression and purification of proteins is well-known in the art and are listed as the methods for making the peptides of the instant claims. Where the specification fails to provide description is in the combination of the NTM combined with anti-microbial agent.
For all of the reasons presented above, one of ordinary skill in the art would not know which of the countless antimicrobial agents of the claims would also be able to be treat microbial inflammation caused by a viral infection. The Applicant’s specification lacks guidance as to which NTMs encompassed by the claim combined with any anti-microbial agent would retain the desired therapeutic activity.
Response to Argument
The applicants response filed on 12/01/2025 has been fully considered but is unpersuasive. The applicants argue that they “assert that this rejection has been overcome in light of the amendment to Claim 1” but do not address the aspect of the rejection regarding the anti-microbial agents.
Scope of enablement
Currently amended claims 1-2, 4, 6, and 8 stand 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 treating a subject for a microbial inflammation caused by a bacterial infection shown in the working example found in the instant specification (Example 1) using the combination of an anti-bacterial antibiotic shown in such example and the NTP comprising instant SEQ ID NO:2, does not reasonably provide enablement for the broad scope of the present 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 make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands 858 F.2d 731,8 USPQ2nd 1400 (Fed. Cir, 1988). They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (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 or unpredictability of the art, and (8) the breadth of the claims.
The claims are drawn to a method of treating microbial inflammation cause by a viral infection in a subject by administering a therapeutically effective amount of an antimicrobial agent and a composition comprising a Nuclear Transport Modifier (NTM) comprising the sequence of instant SEQ ID NO: 2 (elected species). The claims include chronic inflammation and sepsis, etc. (See claim 4). The claims include microbial inflammation localized to the blood, brain, etc. (See claim 6). The claims include inflammation caused by a viral infection including HSV-1, HSV-2, Coronavirus, and HIV type-1, etc. (See claim 8).
The breadth of the claims and The Nature of the Invention: It is noted that MPEP 2111.01 states that "[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow." The claims are broad given the number of disorders encompassed antimicrobial inflammation caused by a viral infection. The claims are broad with respect to the patient population being treated. The claims are broad to the type of anti-microbial agent used in combination with the NTM to treat the broad range of disorders encompassed by the claims.
The State of the Prior Art: The state of the art does not provide guidance regarding the breadth of treatments encompassed by the claims. For example, the prior art reference US2013/0089528 (of record) discloses administering the peptide comprising instant SEQ ID NO: 2 to a subject to treat inflammation caused by diabetes including microbial-related diabetes. However, this reference is silent regarding combining this treating with an anti-microbial. Also, post-filing art of Liu (Nature (2022) 12:18891, scientific reports, of record), teaches
“Atopic Dermatitis (AD) or eczema, a recurrent allergic inflammation of the skin, afflicts 10-20% of children and 5% adults of all racial and ethnic groups globally. We report a new topical treatment of AD by a Nuclear Transport Checkpoint Inhibitor (NTC, peptide of the present invention), which targets two nuclear transport shuttles, importin ad and importin 61. In the preclinical model of AD, induced by the active vitamin D3 analog MC903 (calcipotriol), NTCI suppressed the expression of keratinocyte-derived cytokine, Thymic Stromal Lymphopoietin (TSLP), the key gene in AD development. Moreover, the genes encoding mediators of TH2 response, IL-4 and its receptor IL-4Ra were also silenced together with the genes encoding cytokines IL-1, IL-6, IL-13, IL-23a, IL-33, IFN-y, GM-CSF, VEGF A, the chemokines RANTES and IL-8,and intracellular signal transducers COX-2 and iNOS. Consequently, NTCI suppressed skin infiltration by inflammatory cells (eosinophils, macrophages, and CD4 + T lymphocytes), and reduced MC903-evoked proliferation of Ki-67-positive cells. Thus, we highlight the mechanism of action and the potential utility of topical NTCI for treatment of AD undergoing Phase 1/2 clinical trial”.
However, each disease and disorder encompassed by the claims (any microbial inflammatory disease or disorder caused by a viral infection) have varying mechanisms of pathogenesis and distinct treatment protocols that may or may not be effective. The same heterogeneity and variability exist at the cellular and molecular level which makes treatment of any skin inflammatory disease/disorder unpredictable.
The Predictability or Unpredictability of the Art: The prior art pertaining to the treatment of inflammatory/infectious diseases including skin diseases is highly complex and unpredictable (see prior art description herein).
The Relative Skill of Those in the Art: It is not the skill of those in the art to treat inflammatory disorders broadly caused by any microbe including viruses listed in instant claim 8.
Amount of Guidance/ The Presence or Absence of Working Examples: Applicants reduce to practice the following: Example NTM treatment in combination with PMA (Phorbol Myristoyl Acetate) on the shaved backs on mice (see Examples 1-2, PMA induced inflammation). The specification does not show treatment of any other inflammation disease or disorder including caused by a viral infection and do not provide a nexus for treating PMA induced inflammation of the skin with all of the disorders encompassed by the claims.
The Quantity of Experimentation Necessary: Considering the factors above, the skilled artisan would be burdened with undue experimentation in determining if an NTM comprising the sequence of the instant SEQ ID NO: 2 would be effective at treating any microbial inflammation disease caused by any viral infection. The experimentation required represents years of inventive effort. When the above factors are weighed, it is the examiner's position that one skilled in the art could not practice the invention without undue experimentation. Therefore, in view of the Wands factors, the claims appear to require undue experimentation to use the full scope of the claimed invention.
Response to Argument
The applicants response filed on 12/01/2025 has been fully considered but is unpersuasive. The applicants argue that they “assert that this rejection has been overcome in light of the amendment to Claim 1” but do not address the aspect of the rejection regarding the anti-microbial agents and treating microbial inflammation caused by any viral infection in the subject.
Double Patenting
Response to Argument regarding NSDP rejections
The applicants response filed on 12/01/2025 has been fully considered but is unpersuasive. The applicants argue that claims have been amended but do not provide any reasoning why the NSDP rejections are improper. Thus, the rejections are maintained.
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.
Currently amended claims 1-2, 4, 6, and 8 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 10, 14-16, 18, 20-23, 26, and 28 of copending Application No. 17/275,764 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the combination of copending claims renders obvious the instant claims
Regarding instant claim 1, copending claim 1 recites a method of treating an inflammation disorder by administering a therapeutically effective amount of a composition comprising an NTM, where the NTM comprises reference SEQ ID NO: 2. Reference SEQ ID NO:2 is identical to the instant 28-mer peptide of SEQ ID NO:2: AAVALLPAVLLALLAPCVQRKRQKLMPC. Copending claim 26 recites treating a microbial inflammation in a subject comprising administering to the subject a therapeutically effective amount of an anti-microbial agent and a composition comprising a Nuclear Transport Modifier (NTM). Copending claim 1 recites that the NTM comprises the sequence set forth in reference SEQ ID NO: 2 which is identical to instant SEQ ID NO:2. Further, copending claim 8 recites that the microbial inflammation is caused by a viral infection
Regarding instant claim 2, copending claims do not recite that the NTM composition comprises the anti-microbial agent.
Regarding instant claim 4, copending claim 1 recites that the inflammation is to the skin which meets the limitation of being an organ-specific inflammation.
Regarding instant claim 6, copending claim 1 recites that the inflammation is to the skin.
Regarding instant claim 8, copending claim 8 recites discloses that the microbial inflammation is caused by a viral infection including Herpes Simplex virus-1, Herpes Simplex virus-2, Varicella-Zoster virus, etc.
In view of the high skill level on the art before the effective filing date of the presently claimed invention it is considered that one of ordinary skill in the art would have combined the elements of the copending claims for the rationale of a method to treat a microbial inflammation. It would have been obvious to do such because the copending claims are the preferred embodiments of such method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1-2, 4, and 6 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 18/939,615 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the combination of copending claims renders obvious the instant claims.
Regarding instant claim 1, copending claim 2 recites a method of treating a microbial inflammation disorder by administering a therapeutically effective amount of a composition comprising an NTM, where the NTM comprises reference SEQ ID NO: 2. Reference SEQ ID NO:2 is identical to the instant 28-mer peptide of SEQ ID NO:2: AAVALLPAVLLALLAPCVQRKRQKLMPC. Copending claim 5 recites treating a microbial inflammation in a subject comprising administering to the subject a therapeutically effective amount of an anti-microbial agent and a composition comprising a Nuclear Transport Modifier (NTM). Regarding instant claim 1, copending claim 4 recites discloses that the microbial inflammation is caused by a viral. Regarding instant claim 1, copending claim 2 recites that the NTM comprises the sequence set forth in reference SEQ ID NO: 2 which is identical to instant SEQ ID NO:2.
Regarding instant claim 2, copending claim 5 does not recite that the NTM composition comprises the anti-microbial agent.
Regarding instant claim 4, copending claim 2 recites that the inflammation is to the skin which meets the limitation of being an organ-specific inflammation.
Regarding instant claim 6, copending claim 2 recites that the inflammation is to the skin.
In view of the high skill level on the art before the effective filing date of the presently claimed invention it is considered that one of ordinary skill in the art would have combined the elements of the copending claims for the rationale of a method to treat a microbial inflammation. It would have been obvious to do such because the copending claims are the preferred embodiments of such method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Related prior art is Hawiger (US2013/0089528). US2013/0089528 discloses administering the peptide comprising instant SEQ ID NO: 2 to a subject to treat inflammation caused by diabetes including microbial-related diabetes. Hawiger does not teach or suggest combining this treating with an anti-microbial.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE S HIBBERT whose telephone number is (571)270-3053. The examiner can normally be reached M-F 8:00-5:00.
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/CATHERINE S HIBBERT/Primary Examiner, Art Unit 1658