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 .
Claims 8-17 and 25-31 are pending and examined on the merits, after amendment.
Applicant’s filing of the RCE (amendments and arguments) is acknowledged.
The examiner welcomes a further interview to advance prosecution on the merits.
Election/Restrictions – Withdrawn
Claim Rejections - 35 USC § 112(a)(i)/(pre-AIA ) – Written Description; Maintained;
Modified, Necessitated by Amendment
The following is a quotation 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.
Claims 8-17 and 25-31 remain/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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
To provide evidence of possession of a claimed genus, the specification must provide 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, without specific antibody-Fc regions structurally claimed, the skilled artisan cannot envision the detailed chemical structure of the encompassed variants, including in order to determine what structure + function is present and supported and in applicant’s possession as the time of filing.
In the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111; clearly states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the 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).
Without specific antibody-Fc regions structurally claimed, the skilled artisan cannot envision the detailed chemical structure of the encompassed variants, 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 bovinesequence.
Therefore, the full breadth of the claims are not presently deemed to have been in Applicant’s ‘possession’ and found to meet the written description provision of 35 U.S.C. §112.
Response to Amendments/Arguments - Maintained
See also previous interview summary of record, where the examiner indicated that possession issues remain as to what peptides may be inserted into the now claimed Fc insertion sites and shown to achieve the intended structure + function of the described/claimed invention. Were those peptides found to have achieved such and in possession amended into the base claims, such may overcome the 112(a) rejection, pending the final updated search thereof.
After amendment the above still has not been addressed. As described, that which is inserted is critical/essential to possession and the functionality of the end product – e.g. the internal peptides for inclusion into the Fc region and where inside the Fc region (see e.g. specification para’s 205, 217, 226):
[0205] The engineered antibody obtained by the present invention has, inserted in the Fc region thereof, an internal peptide sequence of a cyclic peptide having a binding ability to a second target molecule different from a first target molecule to be recognized by the antibody and therefore having a binding ability to the first and second target molecules.
[0217] In order to present the internal sequence of a cyclic peptide on the Fc region of an antibody while keeping a target binding activity, an insertion site was searched with reference to the tertiary structure of the Fc region of the antibody. Nine loop portions exposed on the molecular surface and linking secondary structural portions were selected from the Fc region. The loop portions thus selected are shown in FIG. 2. The selected loops include three (T1 to 3) at Top near the hinge of the Fc region, three (M1 to 3) at Middle, and three (B1 to 3) at Bottom. All of their positions on the full Fc amino acid sequence are shown in FIG. 3.
[0226] By using expression vectors obtained by adopting the “B1 group” shown in Example 1 as a peptide insertion position and inserting the internal sequences of the four kinds of cyclic peptides shown in FIG. 1 according to the method of Example 1, preparation of recombinant antibodies and expression evaluation of them were performed also as in Example 1.
As set forth in Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016: 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. Here, the compounds themselves – for which applicant was in possession of and shown to have yielded a structure + functioning end product - still are not claimed. Until such a reasonable search of the invention for which applicant had possession and potential rights to still cannot be carried out, until the claim scope is commensurate therewith (namely, searchable structures in possession).
Claim Rejections - 35 USC § 112(b) – Indefiniteness, Structural Cooperation of the Elements
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.
Claims 8-17 and 25-31 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.
The claims are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are (e.g. the internal peptides for inclusion into the Fc region and where inside the Fc region):
After amendment the above still has not been addressed. As described, that which is inserted is critical/essential to the structural cooperation of all the elements and the functionality of the end product (see e.g. specification para’s 205, 217, 226):
[0205] The engineered antibody obtained by the present invention has, inserted in the Fc region thereof, an internal peptide sequence of a cyclic peptide having a binding ability to a second target molecule different from a first target molecule to be recognized by the antibody and therefore having a binding ability to the first and second target molecules.
[0217] In order to present the internal sequence of a cyclic peptide on the Fc region of an antibody while keeping a target binding activity, an insertion site was searched with reference to the tertiary structure of the Fc region of the antibody. Nine loop portions exposed on the molecular surface and linking secondary structural portions were selected from the Fc region. The loop portions thus selected are shown in FIG. 2. The selected loops include three (T1 to 3) at Top near the hinge of the Fc region, three (M1 to 3) at Middle, and three (B1 to 3) at Bottom. All of their positions on the full Fc amino acid sequence are shown in FIG. 3.
[0226] By using expression vectors obtained by adopting the “B1 group” shown in Example 1 as a peptide insertion position and inserting the internal sequences of the four kinds of cyclic peptides shown in FIG. 1 according to the method of Example 1, preparation of recombinant antibodies and expression evaluation of them were performed also as in Example 1.
Here, the compounds themselves – for which applicant has shown the structural cooperation of all the elements as yielding a structure + functioning end product - still are not claimed. Until such a reasonable search of the invention for which applicant had metes and bounds coverage upon and potential rights to still cannot be carried out, until the claim scope is commensurate therewith (namely, searchable structures with the structural cooperation of all those elements fully set forth).
Claim Rejections - 35 USC § 103 – Obviousness, Held in Abeyance –
Until 35 USC 112(a) & (b) Rejections Addressed –
Reasonable Updated Search Not Possible –
Until Possession & Structural Cooperation of Elements Addressed w/in Claim Scope
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 8-17 and 25-31 remain/are rejected under 35 U.S.C. 103 as being unpatentable over D1-D6 as cited in the international authorities disposition in the related PCT over similar/overlapping claim scope for which the examiner, based on the broadest reasonable scope (BRI) and breadth as still claimed (see also 35 USC 112(a) Written Description rejection below) here within product claims 17-24 and method claims 8-16 finds equivalently prima facie obvious thereover under the equivalent to lack of inventive step standard applied internationally, absent evidence to the contrary:
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Response to Amendments/Arguments – Held in Abeyance Per Above
Per the interview summary of record, applicant’s amendments and arguments have been fully considered but are not found persuasive (except as to new claim 27, not found reasonably taught or suggested as to these specific peptide SEQ ID NO: 7, Fc insertion sites; but see 35 USC 112(a) rejection below as to new claim 27 still though). Un updated google search was carried out as to the State of the Art on IgG antibodies modified at both Fc region &Fab regions following review of claim scope amendments. The prior art recited but not relied upon generally discussed with applicant's representative during a recent interview (summary attached), included the following:
JP 2005503344 (Dyax Corp.; equivalent - WO 02/086070);
AU 5755499 (Ilexus Pty Ltd.; equivalent - WO 00/15214);
WO 2016054603 (City of Hope); and
Valeur et al. New Modalities for Challenging Targets in Drug Discovery. Chem. Int. Ed. 2017, 56, 10294. https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201611914.
Namely, that the prior art of record as applied or in view of the State of the Art appears to contemplate the genus of claim 8 still following amendments. Where the prior art of record applied in the rejection is still deemed to provide the motivation/rationale to arrive at the instantly claimed invention, including new claims 25-26 (routine selection of IgG1 antibodies from known options), even if not teaching or suggesting new claim 27 as to the peptide SEQ ID NO: 7 Fc region insertion sites now claimed. (NOTE: But see 112(a) written description rejection above as to lack of possession as to what peptides may be inserted therein and were shown to achieve the intended structure + function of the described/claimed invention. Were those peptides found to have achieved such and in possession amended into new claim 27, such may overcome the 112(a) rejection pending the final updated search thereof). Notwithstanding new claim 27, all remaining claims 8-26 remain prima facie obvious over the prior art of record as applied and/or in view of the State of the Art that is was known to carry out Fc and Fab region modifications of IgG antibodies with cyclic peptide insertions therein.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAURY AUDET whose telephone number is (571)272-0960. The examiner can normally be reached on M-Th. 7AM-5:30PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/MAURY A AUDET/Primary Examiner, Art Unit 1654
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