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 5/4/26. Claims 1, 5-11, or 16-19 are pending and under examination.
Withdrawn Rejections
The objection to the specification is withdrawn. The amendments have removed the phrase “preparing a patient” from the claims and so this phrase no longer needs antecedent basis in the specification.
The §112b rejections are withdrawn in light of the amendments.
The §112d rejection is withdrawn; the rejected claims have been canceled.
Maintained Rejections and New Rejections Necessitated by Amendment
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 1, 7-11, 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 a modified ligand-gated ion channel (LGIC) under the control of any transcriptional control element governing cell-specific expression in dorsal horn neurons. While there is the requirement that 95% identity is preserved, no specific sequence is conserved or identified as responsible for the claimed function. 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 5% of these sequences (11 amino acids) 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 with 95% identity to certain sequences, 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 “95% identity” where 11 of the 224 amino acids can be changed anywhere in the sequence in any combination of consecutive or non-consecutive residues independently to any of the other 19 amino acids.
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, 7-11, and 18-19 do not meet the written description requirement. Claims 6 and 17 are not included in this rejection. Claims 5, 6, 16, and 17 require specific mutations at specific positions.
Claims 1, 7-11, 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 α7 nicotinic acetylcholine ligand binding domain altered up to 5% 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., claim 1), the claim includes modifying any combination of up to eleven (11) 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 conserved 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 modify a human spinal cell for therapy. 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.
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, 7-11, and 18-19 do not meet the enablement requirement in full.
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, 5-11, or 16-19 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. With respect to the modified ligand channel having at least 95% identity to one of SEQ ID NOs: 18-20, the reference patent does not specify the sequence of the channel.
“The specification can be used as a dictionary to learn the meaning of a term in the patent claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999)(‘[W]ords in patent claims are given their ordinary meaning in the usage of the field of the invention, unless the text of the patent makes clear that a word was used with a special meaning.’); Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250, 48 USPQ2d 1117, 1122 (Fed. Cir. 1998) (‘Where there are several common meanings for a claim term, the patent disclosure serves to point away from the improper meanings and toward the proper meanings.’). See also MPEP § 2111.01. Further, those portions of the specification which provide support for the patent claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the patent. In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized ‘that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim,’ but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent which provides support for the patent claim. According to the court, one must first ‘determine how much of the patent disclosure pertains to the invention claimed in the patent’ because only ‘[t]his portion of the specification supports the patent claims and may be considered.’ The court pointed out that ‘this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined.’’’ MPEP §804(II)(B)(1)
In this case, the specification may be inspected for the meaning of the phrase “a modified ligand-gated ion channel” and “a modified α7 nicotinic acetylcholine ligand binding domain” as well as for those sections which support these phrases, e.g., under §112(a). As noted, both the instant and reference claims are directed to the same mutations (compare reference claim 1 to instant claim 6) and in support of sequences with these changes as well as the phrases above the reference document also discloses SEQ ID NOs: 18-20, which are identical to the instant sequences.
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, which anticipates the broader, instantly claimed “delivering to a patient”. While the reference claims include the administration of the exogenous ligand, this step is not excluded from the instant method (“comprising”).
Response to Arguments
Applicant's arguments filed 5/4/26 have been fully considered but they are not persuasive.
Regarding the written description rejection, Applicant argues that the claims are amended to recite “specific sequences” for the modified α7 domain. This is not persuasive because the claims have not been amended to recite a specific sequence but rather encompass altering an arbitrary 5% of the claimed sequences.
Applicant argues that “the fact that claims 6 and 17 are not rejected” is evidence that the written description rejection is met. This is not persuasive because this was explicitly addressed in the previous office action. Claims that require specific modifications have not been rejected. Claims such as claim 6 requires specific modifications to the parent sequence. The assumption is that these specific mutations alone result in Applicant’s claimed function of having a modified ligand-gated ion channel with the claimed function of responding to the exogenous ligands in claim 8. In this case, there is no objective rationale for doubting that every possible mutation of 5% of the claimed sequences will possess the claimed function so long as that sequence contains, e.g., an alanine at position 79 (claim 5). If this were not the case—if one would need to make and test each variation within the scope of claim 5 to determine if this property is present—then the claim would fail §112a as well. While this making and testing might be within the scope of routine experimentation and therefore enabled, the written description requires the skilled artisan to be able to envisage these specific sequences a priori without such testing.
This highlights the reasoning that the broader claims do not meet the written description. The Examiner has not set forth a reasoning to doubt that a protein having 95% identity to the claimed sequences will function so long as they possess the claimed mutations in, e.g., claims 5 and 6. In contrast, the Examiner has set forth reasoning why a sequence that requires no specific amino acids does not meet this bar. Claim 5 requires mutations to short side chain amino acids (A or G) and one could not envisage whether or not position 79 would possess this function with P or C. Further, there are certainly some residues that are responsible for the function but the specification and art of record does not allow the skilled artisan to envisage the 11 mutations that would still meet the claimed functions. The claimed invention is not simply an arbitrary sequence but a nucleic acid encoding a modified ligand-gated α7 nicotinic acetylcholine ligand binding domain that is activatable by the breadth of any exogenous ligand or more specifically the ligands in claim 8.
Given the disclosure and art of record, one could not envisage which amino acids contribute to binding, which amino acid positions could be altered, which substitutions are viable at those positions, or any of the other requirements to meet the written description requirement. While Applicant argues “those of skill in the art can, based on the teaching and examples in the specification, identify suitable substitutions” but notably does not offer any examples of a “suitable substitution” that is not already claimed nor point to any particular portion of the specification which would allow one to identify these substitutions without making and testing each one. 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.
Regarding the double patenting rejection, Applicant argues that a terminal disclaimer will be filed “if appropriate” upon withdrawal of all remaining rejections. This is not responsive. The actual filing of a terminal disclaimer or filing a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims is necessary for further consideration of the rejection of the claims; nonstatutory double patenting rejections, including provisional ODP rejections, are not held in abeyance (MPEP §804(I)(B)(1)).
Allowable Subject Matter
Reasons for allowance are of record in the office action mailed 2/2/26.
Conclusion
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 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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Adam Weidner/Primary Examiner, Art Unit 1675
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