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.
DETAILED ACTION
This action is in response to claims filed 6/8/23. Claims 1-19 are pending and under examination.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of the earlier filing date of the 62/473630 document as follows:
Claim 5-6, 16-17: the priority document makes no mention of, e.g., the position 131 or specifically the L131G mutation.
Claim 8: the priority document makes no mention of, e.g., tropane, nor does there appear to be implicit/inherent support for such a limitation.
As such, these claims and those which depend from these claims have an effective filing date of 3/20/2018, as these limitations first appear in priority document PCT/US2018/023364.
Note that Applicant has not pointed to any specific support for the method of claim 11. Rather, every method embodiment (21-45 starting at page 33) includes the addition of the exogenous ligand to treat the subject. There is no verbatim support for a method of “preparing a patient” as this phrase does not appear anywhere in the specification nor in the priority documents. MPEP §608.04(a) indicates that the omission of a step may introduce new matter. While the claims are not new matter in this application because they were included on the day of filing, this could indicate that the claims are not entitled to the priority documents as those also do not have verbatim support; this method was proposed but not entered during prosecution in parent application 16/493387, now US 11713470. In that application, Applicant stated the method was not new matter because it was “supported by at least the originally filed claims and specification”. This does not point to any particular support for this method.
However, it is not clear that this omission of a step is consonant with the fact patterns in, e.g., Wertheim (541 F.2d 257, 191 USPQ 90), where the specification made unequivocal statements that certain limitations were required; see also MPEP §2163.05(I)(A). Thus, the Examiner does not refuse the right of priority based on this method at this time (MPEP §215).
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required:
The specification lacks clear antecedent basis for the phrase “preparing a patient for a treatment”.
Claim Interpretation
There is no special definition of the term “packagable” nor any specific structure associated with this limitation. Thus, any viral genome will be considered “packagable” and “capable of being packaged”.
Claim Rejections - 35 USC § 112
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 5 and 16 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 claim(s) currently use exemplary language (e.g. such as, optionally, preferably, in particular, etc.). Such language may or may not further limit the claim and results in confusion over the claim scope. See MPEP § 2173.05(d) which states that “[d]escription of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim". In this case, it is unclear if the claim lists the potential sites of mutation, where any mutation is within the claim scope, or if the claim is listing potential sites of mutation followed by the specific mutations required at those sites. Position 115 does not have any exemplary mutations, suggesting that perhaps the specific examples are just possibilities and not claim limitations. On the other hand, a lack of example for position 115 may indicate that any mutation at 115 is within the claim scope, while mutations at 79 are limited to either A or G. To clarify the claim scope, exemplary language should either be clearly, positively recited as a claim limitation or removed from the claim altogether.
Therefore, claims 5 and 16 are indefinite.
Claims 4, 10, 15, and 19 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 4 and 15 set forth sequence identity limitations. For example, claim 4 requires an element having “at least 75 percent sequence identity to a sequence set forth in” certain sequences. However, the term “a sequence” is ambiguous. In one case, the sequence must be 75% identical across the whole of, e.g., SEQ ID NO: 18. In another, SEQ ID NO: 18 comprises the sequence tt, and so any sequence which contains “tt” is 100% identical to “a sequence set forth in” SEQ ID NO: 18; see e.g., specification paragraph 54, which supports the interpretation that identity need not be evaluated across the whole of the sequences.
Claim 10 refers to the nucleic acid of claim 9, and therefore is a composition of matter claim. Claim 10 requires that this nucleic acid comprise:
AAV ITR sequences flanking the gene for expressing a modified ligand-gated ion channel
Producing a sequence of a packagable recombinant AAV genome, or
A self-complementary AAV genome comprising the gene for expressing a modified ligand-gated ion channel.
While the first and third element of the list recites an additional component to the structure, the second element is an active method step that requires “producing” something. Adding process steps to a product claim is indefinite as it creates confusion as to when direct infringement occurs; MPEP §2173.05(p)(II).
Claim 19 recites “the chronic pain in the patient”. Claim 11 is for preparing a patient for treatment for relieving chronic pain; there is no requirement that the patient have chronic pain and so there is a lack of antecedent basis for “the chronic pain in the patient”. For example, a patient with no such pain might still be “prepared” for potential treatment by practicing the method steps whether or not the subject has chronic pain at the time of administration.
Therefore, claims 4, 10, 15, and 19 are indefinite.
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 1-5, 7-16, and 18-19 are 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 claimed invention.
One means of providing adequate written description and evidence of possession of a claimed genus is through providing sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In this case, the specification discloses certain species but does not correlate any particular shared structure within these species to the genus as a whole responsible for the required function; there is no identification of any particular structure that must be conserved throughout the genus. For example, claim 1 encompasses any modified ligand-gated ion channel (LGIC) under the control of any transcriptional control element governing cell-specific expression in dorsal horn neurons. There is no shared structural requirements between, e.g., a CCK promoter, NTS promoter, or the genus of all control elements specific to these cells. Similarly, there is no common structure amongst all possible ligand-gated ion channels, as they will be responsive to different ligands and possess different structures. Moreover, there is no common “modification” that will alter a native ligand-gated ion channel to be responsive selectively to an exogenous, non-native ligand. Rather, this will depend on the channel being modified. Thus, those skilled in the art are led to broad genera with nothing in common beyond their function or intended use, which fails to adequately describe those genera.
In a second way, the specification might provide a representative number of species for the claimed genus that would convey to the artisan possession of the whole genus. However, in this case, the species disclosed to not represent the full breadth of all possible members of the genus. For example, while the instant specification names the a7 nicotinic acetylcholine ligand as well as certain, specific mutations at specific residues, the specification does not describe mutations across the breadth of SEQ ID NOs: 18-20. As such, direction to arbitrarily alter up to 25% of these sequences (claim 4) does not convey to the skilled artisan that Applicant actually knew the identity of the sequences which would and would not continue to function.
A “patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”), see MPEP 2163 (II)(A)(3)(a)(ii). Where a genus is claimed, such as in claim 1 for any modified α7 nicotinic acetylcholine ligand binding domain, a “sufficient variety of species to reflect the variation within the genus” is required. SEQ ID NO: 18 is 224 amino acids long while only 13 positions are named and not all of those positions describe the particular mutation to be made. This does not represent the variation within “75% identity”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Therefore, claims 1-5, 7-16, and 18-19 do not meet the written description requirement. Claims 6 and 17 are not included in this rejection. Claims 6 and 17 require specific mutations at specific positions and do not explicitly claim alterations to a broad number of other positions (e.g., the claims do not recite 75% identical).
Claims 1-5, 7-16, and 18-19 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 modified α7 nicotinic acetylcholine ligand binding domain comprising a combination of mutations in, e.g., claim 6, does not reasonably provide enablement for the composition and its uses as broadly as claimed. 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.
The nature of the invention is using a neuron-specific transcriptional control unit to express a modified LGIC in dorsal horn neurons, where the ligand is modified to respond to an exogenous ligand, thereby placing the LGIC in a specific cell population to be activated when the exogenous ligand is administered. However, the claims are drawn broadly to any modified ligand gated ion channel (LGIC). Claims 4 and 15 recite the α7 nicotinic acetylcholine ligand binding domain altered up to 25% of the sequence from a parent sequence. There are certain residues which are disclosed as being modified (e.g., claim 17). However, these are only limitations in certain claims, indicating that in others (e.g., claims 1 and 4), the claim includes modifying any combination of over 50 residues to arrive at one of the other 19 amino acids, essentially encompassing a genus vastly larger than what is disclosed. Finally, the modified α7 must respond to certain, specific chemicals (claim 8), despite not being claimed by any form of structure in claim 1.
While skill in the art is high, predictability is low. Specifically, the disclosure has not shown (1) which portions of which modified channel protein are critical to the activity of the protein; (2) what modifications (e.g., substitutions, deletions, or additions) one can make to these LGICs that will result in protein variants with the same function/activity as the claims require, and (3) any guidance on how to use the breadth of such variants, which would inevitably include both active and inactive variants, to modulate cell membrane potential or to “prepare” the subject. The state of the art is such that the relationship between the sequence of a protein and its activity is unpredictable and not well understood, and that certain positions in the sequence are critical to the protein’s structure/function relationship and can only tolerate only relatively conservative substitutions or no substitutions at all.
The problem of predicting protein and DNA structure from sequence data and in turn utilizing predicted structural determinations to ascertain functional aspects of the protein and DNA is complex. While it is known that many amino acid substitutions are generally possible in any given protein, the positions within the protein's sequence where such amino acid substitutions can be made with a reasonable expectation of success are limited. Certain positions in the sequence are critical to the protein's structure/function relationship, e.g. such as various sites or regions directly involved in binding, activity and in providing the correct three-dimensional spatial orientation of binding and active sites. These regions can tolerate only relatively conservative substitutions or no substitutions; see Wells (IDS 10/26/23 NPL citation 33). However, while Applicant has disclosed certain, specific mutations in certain, specific sequences, this leaves most positions and most sequences undisclosed, leaving it to others to determine if and how these other domains may be altered while still preserving the required functions. This would require extensive trial-and-error experimentation on the part of others as they would need to generate the large number of variants and derivatives encompassed by the claims and screen for themselves to determine which accomplish the goals of the claim. This is undue experimentation.
Finally, claim 12 requires the nucleic acid “is delivered” to the dorsal horn. There is no special definition of the term “delivered” and so the nucleic acid reaching the dorsal horn by any means is within the meaning of this phrase. For example, intravenous administration, where the nucleic acid eventually arrives at the dorsal horn, means the nucleic acid “is delivered” to the dorsal horn. However, under §112(d), a dependent claim must provide a further limitation. This means that claim 11 need not have the nucleic acid ever reach the dorsal horn. Yet, this is the only mechanism by which the disclosed methods function. The nucleic acid of claim 11 contains a regulatory element that is specific to dorsal horn neurons; if the nucleic acid is not delivered to the dorsal horn, it has not “prepared” the subject as the claim requires. This is exemplified in instant claim 19, where the exogenous ligand is administered in “an amount effective” to activate the modified LGIC; however, if the nucleic acid is not delivered to the dorsal horn, the LGIC is not expressed and there is no amount of an exogenous ligand which can activate a non-existent protein. It would be undue experimentation on the part of others to determine how to use a nucleic acid that only expresses in the dorsal horn without ever delivering the nucleic acid to said dorsal horn as there is no expectation of any utility or effect in other areas. Note that claim 12 states “the dorsal horn of the spinal cord”, but the spinal cord is the only location of the dorsal horn, so does not serve to add a limitation.
The standard of an enabling disclosure is not the ability to make and test if the invention worked but one of the ability to make and use with a reasonable expectation of success.
"[T]o be enabling, the specification..., must teach those skilled in the art how to make and use the full scope of the claimed invention without 'undue experimentation.'" Wright, 999 F.2d at 1561, 27 USPQ2d at 1513 (emphasis added), quoted in Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997). Thus, "there must be sufficient disclosure, either through illustrative examples or terminology, to teach those of ordinary skill how to make and how to use the invention as broadly as it is claimed." (emphasis added) In re Vaeck, 947 F.2d 488, 496 & n. 23, 20 USPQ2d 1438, 1445 & n. 23 (Fed. Cir. 1991), quoted in Enzo Biochem, Inc. v. Calgene, lnc., 188 F.3d 1362, 1372, 52 USPQ2d 1129, 1138 (Fed. Cir. 1999).
Therefore, claims 1-5, 7-16, and 18-19 do not meet the enablement requirement in full.
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.
Claims 2, 3, 13 and 14 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 1 recites a modified ligand gated ion channel, which comprises a modified ligand binding domain. The channel is a modified α7 nicotinic acetylcholine ligand binding domain. Since the channel is an α7 binding domain and the channel comprises a binding domain, the channel binding domain must be α7 in claim 1. However, the only limitation of claim 3 is specifying that the binding domain is α7, which does not appear to add any further limitation. The same facts are true of claims 11 and 14.
Claims 2 and 13 recite four regulatory elements. Claims 1 and 11 require a regulatory element and claims 2 and 13 recite every regulatory element disclosed in the specification. Thus, it is not apparent from the disclosure that claims 2 or 13 provide a further limitation.
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.
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 1-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11713470. Although the claims at issue are not identical, they are not patentably distinct from each other because:
The methods of the reference claims use a nucleic acid composition that meets every limitation of the instant claimed composition, including a dorsal horn specific regulatory element, a modified α7, and the same specific modifications. Thus, the reference claims anticipate the instant composition. The method of the reference claims also anticipates the instant methods as the reference method includes delivering the composition to the dorsal horn. While the reference claims include the administration of the exogenous ligand, this step is not excluded from the instant method (“comprising”).
Note that instant claim 19 includes this administration step. However, instant claim 19 does not require the nucleic acid is delivered to the dorsal horn (see enablement rejection above), which is a requirement of the reference claims. While claim 12 requires this delivery, claim 12 does not require the administration. As such, there is no statutory double patenting rejection.
Allowable Subject Matter
There is no prior art rejection made of record. The claims are allowable over the prior art for the reasons set forth in the parent application 16/493387, now US 11713470. Briefly, the closest prior art is Sternson (US 20180009862; IDS 10/26/23). The composition of Sternson differs from instant claim 1 solely in that Sternson teaches the genus of “neuron specific promoters” while all of the instant claims require a dorsal horn neuron specific promoter. When looking to examples, Sternson only exemplifies brain neurons (cortical neurons). Thus, while Sternson teaches modulating channels and treating, e.g., fibromyalgia, Sternson does not provide sufficient guidance to suggest that modulating channels in the dorsal horn would treat the disclosed channelopathies. The Examiner did not discover art to correct this deficiency. While there was a general understanding in the art that dorsal horn neurons play a role in pain such as fibromyalgia—see e.g., Stahl (form 892)—it does not appear that the art recognized dorsal horn channels were a viable or expected therapeutic target. The art is missing 1) an expectation that modulating dorsal horn neuron channels would treat one of the channelopathies in Sternson and 2) a reason to modify dorsal horn neuron channels for non-therapeutic reasons. In the absence of one of those two teachings, there is insufficient motivation to substitute the central brain neuron specific promoter of Sternson with a dorsal horn specific neuron as instantly claimed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ADAM M WEIDNER whose telephone number is (571)272-3045. The examiner can normally be reached M-T 9-18; W-R 9-15.
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/Adam Weidner/ Primary Examiner, Art Unit 1675