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 .
Priority
Applicant is reminded that in order for a patent issuing on the instant application to obtain priority under 35 U.S.C. 119(a)-(d) or (f), 365(a) or (b), or 386(a) or (b), based on priority papers filed in a parent or related Application No. 15322021 (to which the present application claims the benefit under 35 U.S.C. 120, 121, 365(c), or 386(c) or is a reissue application of a patent issued on the related application), a claim for such foreign priority must be timely made in this application. To satisfy the requirement of 37 CFR 1.55 for a certified copy of the foreign application, applicant may simply identify the parent nonprovisional application or patent for which reissue is sought containing the certified copy.
Specification
The abstract of the disclosure is objected to because the term “said”. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Claim Objections
Claims 11, 12, and 17-19 are objected to because of the following informalities: Inserting the term “Toll-like receptor 4” before the abbreviation (TLR-4) in these claims would help the skilled artisan understand the abbreviation.
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 17 and 20-30 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 for detecting Toll-like receptor 4 (TLR-4) in a sample or a sample from a subject comprising contacting the sample or subject with a single stranded nucleic acid according to claim 1 or a complex or compound thereof; isolating a sample from the subject and detecting TLR-4 in the sample; a method of decreasing one or more symptoms of the pathology the diseases set forth in claim 20(21); and, does not reasonably provide enablement for detecting TLR-4 in a subject comprising administering the nucleic acid of claim 1 to the subject with no further steps; a method of increasing one or more symptoms of the diseases set forth in claim 20(21) in a subject in need thereof comprising administering the nucleic acid or a complex, compound of pharmaceutical composition thereof to the subject in need thereof. 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.
The claimed invention embraces detecting TLR-4 in a sample or a subject comprising administering the single stranded nucleic acid of claim 1 to the sample or subject. The specification enables using the single stranded nucleic acid to detect TLR-4 in a sample or a sample of a subject, but is not enabled for in vivo method of detecting TLR-4 in a subject using the nucleic acid without a detectable moiety.
The claimed method does not embrace any method steps to enable a skilled artisan to detect TLR-4 in a subject without isolating a sample form the subject because other than isolating the sample and detecting TLR-4 there are no steps for detecting TLR-4 in the subject. See pages 15, 16, 24-34, 47 and 55.
The specification discloses in vitro methods for detecting TLR-4 in a sample. Several pages of the specification (Page 47) contemplate imaging method of a cell, tissue or organ expressing TLR4 wherein the aptamer is attached to a complex comprising a functional group being a detectable moiety. The claimed method would require a method step of using a detectable moiety with the TLR-4 aptamer for detecting TLR-4 in a subject.
Thus, claim 17 is not fully enabled.
Instant claims 20-30 embraces increasing at least one symptom of multiple sclerosis, ischemic heart disease, retinal degenerative disease, drug addiction, or sepsis in a subject in need thereof by administering the single stranded nucleic acid of claim 1 to the subject.
Gooshe et al. (Rev Neurosci. 2014, 25: 713-739, cited on an IDS) disclose the role of TLRs in multiple sclerosis (MS) and possible target for therapeutic purposes.
Hernandez-Jimenenz (Mol Ther Nucleic Acids 28, 124-235, 2022, and JAMA Neurol. 2024, both cited on an IDS) disclose clinical trials using TLR-4 DNA binding aptamers.
Pages 1-2 of the specification disclose prior art teaching using TLR-4 antagonist to treat the conditions set forth in claims 20-30.
The specification discloses TLR-4 aptamers treated stroke in a murine model. See pages 34 and 54-55.
In view of the teaching in the prior art of record and the as-filed specification one of skill in the art would want to decrease and not increase a symptom of these diseases. The single stranded nucleic acid targets TLR-4 and would result in decreased TLR-4 expression. The diseases set forth in claims 20-30 are associated with TLR-4 expression and decreasing TLR-4 expression in a subject having any of these diseases or disorders would result in at least one symptom of the disorders or diseases would be decreased not increased.
In addition, with respect to retinal degenerative disease, the claimed method is only enabled for directly administering the nucleic acid of claim 1 to an eye of the subject and not for using a genus of administration routes to decrease one or more symptoms of retinal degenerative disease. The specification does not appear to provide a working example of the method. Example 4 discloses intraperitoneal injection of different amounts of SEQ ID NO: 2 to mice subjected to induction of a focal cerebral ischemia. The prior art teaches that direct administration of a nucleic acid to an eye of a subject is the only method to deliver the nucleic acid to observe a therapeutic effect or decreasing a symptom of an eye disorder or disease. See page 621 of Smith (Annu review Pharmcol Toxicol 59: 605-630, 2019, cited on an IDS). The claimed method directed to retinal degenerative disease is only enabled for direct administration of the single nucleic acid to an eye of the subject.
Thus, instant claims 20-30 are not fully enabled.
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 16-30 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.
Claims 16-30 recite the limitation "the same". There is insufficient antecedent basis for this limitation in the claim. The metes and bounds of the terms are undefined because it is not apparent what the term is referring to.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 3 is dependent on claim 1 and claim 1 is limited to an aptamer comprising at least 94% to SEQ ID NO: 1 or 2. However, claim 3 does not further limit claim 1 because the limitations (a) and (b) in the claim embrace aptamers having less than 94% identity to SEQ ID NO: 1 or 2. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Improper Markush Rejection
Claims 20-30 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of improving one or more symptoms of multiple sclerosis, ischemic heart disease, retinal degenerative disease, drug addiction or sepsis is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
Each disease or disorder listed above requires a different subject and/or has a different set of symptoms. The symptoms for each disease or disorder do not share structural similarity or common use.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-16, 18-20, and 28-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12655435. Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims embrace improving one or more symptoms of the pathology of sepsis in a subject in need thereof comprising administering an aptamer comprising SEQ ID NO: 1 or 2, wherein the aptamer inhibits TLR-4 in the subject. The limitations of claims 2-16, 18-20 and 28-30 are recited in the claims 2-17 of ‘435..
Claims 1-16, 18-21, 24-27 and 29-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 11591603, cited on an IDS. Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims embrace a method to improve one or more symptoms of the pathology of ischemic heart disease, retinal degenerative disease, or drug addiction in a subject in need thereof comprising administering to the subject an effective amount of an active compound comprising at least one nucleic acid aptamer or chemically modified variant thereof, wherein said at least one nucleic acid aptamer or chemically modified variant thereof specifically binds to at least one target site on the extracellular domain of human TLR-4 on at least one target cell, wherein (i) the specific binding of the at least one nucleic acid aptamer or chemically modified variant thereof to the extracellular domain of human TLR-4 results in a decrease in TLR-4 activity; and (ii) the decrease in TLR-4 activity improves one of more symptoms of the pathology of ischemic heart disease in the subject, wherein the at least one nucleic acid aptamer or chemically modified variant thereof comprises a sequence at least 70% identical to SEQ ID NO: 1 or SEQ ID NO: 2. The limitations of dependent claims 2-16 are recited in claims 2-24 of ‘603. The administration step in claim 29 would be an obvious variant of the treatment methods in claim ‘252 since these routes are routinely used in the art to deliver a nucleic acid to a subject. See column 32 of ‘603.
Claims 1-23 and 29-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 10808252, cited on an IDS. Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims embrace a method to improve one of more symptom of the pathology of multiple sclerosis in a subject in need thereof comprising administering to the subject an effective amount of an active compound comprising at least one nucleic acid aptamer or chemically modified variant thereof, wherein said at least one nucleic acid aptamer or chemically modified variant thereof specifically binds to at least one target site on the extracellular domain of human TLR-4 on at least one target cell, wherein (i) the specific binding of the at least one nucleic acid aptamer or chemically modified variant thereof to the extracellular domain of human TLR-4 results in a decrease in TLR-4 activity; and (ii) the decrease in TLR-4 activity improves one of more symptoms of the pathology of multiple sclerosis in the subject, wherein the at least one nucleic acid aptamer or chemically modified variant thereof comprises a sequence at least 70% identical to SEQ ID NO: 1 or SEQ ID NO: 2, or a combination thereof; and a method for imaging TLR-4 in vivo in a subject with multiple sclerosis comprising (i) administering to the subject an active compound comprising at least one nucleic acid aptamer or chemically modified variant thereof, wherein the at least one nucleic acid aptamer or chemically modified variant thereof specifically binds to at least one target site on the extracellular domain of human TLR-4 on the surface of at least one target cell in said subject; and, (ii) detecting the binding of said at least one nucleic acid aptamer or chemically variant thereof to target cells which express TLR4 in said subject, wherein the at least one nucleic acid aptamer or chemically modified variant thereof comprises a nucleic acid sequence at least 70% identical to SEQ ID NO: 1 or SEQ ID NO: 2, or a combination thereof. The limitation in dependent claims 2-15 are recited in claims 2-30 of ‘252. Claim 15 of ‘252 recites the limitations in instant claim 23. The administration step in claim 29 would be an obvious variant of the treatment methods in claim ‘252 since these routes are routinely used in the art to deliver a nucleic acid to a subject. See column 33 of ‘252.
Claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10196642, cited on an IDS. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims from ‘642 embrace a pharmaceutical composition comprising SEQ ID NO: 1 or 2; a method for detecting TLR-4 in sample using an aptamer comprising SEQ ID NO: 1 or 2; an in vitro method of inhibiting TLR-4 in sample containing TLR-4 using the aptamer; a method for the treatment of a pathology characterized by an increase in expression of TLR-4 and/or an increase in activation of TLR-4 comprising administering the aptamer to a subject in need thereof, wherein the administration of the aptamer to the subject results in a decrease in expression of TLR-4 and/or a decrease in activation of TLR-4, wherein the pathology characterized by an increase in expression of TLR-4 and/or an increase in activation of TLR-4 is selected from the group consisting of stroke, acute myocardial infarction, sepsis, atherosclerosis, multiple sclerosis, rheumatoid arthritis, a retinal degenerative disease, and drug addiction. Claims 4-14 and 19-20 of ‘642 read on the limitations set forth in dependent claims 2-15, and 20. The ‘wherein’ clauses in claims 23 and 25 when carrying out the method in a subject having MS or ischemic heart disease. The administration step in claim 29 would be an obvious variant of the treatment methods in claim ‘642 since these routes are routinely used in the art to deliver a nucleic acid to a subject. See column 32 of ‘642.
Claims 1, 2, 3, 5, 6, 8, and 16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of copending Application No. 19650493 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims embrace a pharmaceutical composition comprising an aptamer comprising SEQ ID NO: 1 or 2. SEQ ID NO: 3 recited in the claims of ‘493 is 100% identical to SEQ ID NO: 1.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 3, 5, 6, 8, and 16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19145792 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims embrace a pharmaceutical composition comprising an aptamer comprising SEQ ID NO: 1 or 2. SEQ ID NO: 1 recited in the claims of ‘792 is 100% identical to SEQ ID NO: 2.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
The single stranded nucleic acid having at least 94% to either SEQ ID NO: 1 or 2 as recited in instant claim 1 and used in the methods recited in the instant claims are free of the prior art. The closest prior art is an oligonucleotide with 54% identity to SEQ ID NO: 1. See SEQ ID NO: 52404 in US 20110131679.
Conclusion
See attached PTO-326 for disposition of claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian Whiteman whose telephone number is (571)272-0764. The examiner can normally be reached on Monday thru Friday; 6:00 AM to 3:00PM.
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/BRIAN WHITEMAN/ Primary Examiner, Art Unit 1636
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