DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's amendment and remarks, filed 12/2/25, are acknowledged.
Claims 32, 76-77, 90-93 have been amended.
Claims 32, 76-77, 90-93 are pending and are under examination
In view of Applicant’s remarks, the rejection under 112b and 112a over the limitation reciting wherein SEQ ID NO: 2 is numbered from 2-308 is withdrawn. In claim 32, each recited position corresponds to the position in SEQ ID NO: 2 as numbered 2-308. In other words, the first position in SEQ ID NO: 2 is numbered 2, the second position in SEQ ID NO: 2 is numbered 3, and so on. Therefore, the residue numbered R167 in the instant claims, for example, corresponds to the 166th position in SEQ ID NO: 2.
The other 112b rejection and the prior art rejections are withdrawn in view of Applicant’s claim amendment.
The 112a rejection below has been modified to the extent necessary to address Applicant’s claim amendments.
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 32, 76-77, 90-93 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. Specifically, there is insufficient written description to demonstrate that applicant was in possession of the claimed genus of variant G-CSFR and variant G-CSF.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See MPEP 2163.
The instant claims are directed to a system comprising a receptor comprising a variant ECD of G-CSFR and a variant GSF. The claims encompass a large genus of structurally distinct variants that are at least 85% identical to SEQ ID NO: 1 and 2, except wherein the variants comprise at least one mutation in site II and/or site III interface region selected from a list of mutations recited in claim 32 The claims encompass an enormous genus of variant G-CSFR and G-CSF. For example, SEQ ID NO: 2 is 307 amino acids in length and variants 85% identical thereto could differ in up to 45 amino acid positions, in any combination, in addition to the specifically recited substitutions recited in the claims. The claims could encompass variants having 85% identity that comprise amino acid additions or deletions. The claims also encompass a genus of specific site II and site III substitutions in any combination. For example, the claims could encompass G-CSFR variant with one of the 16 site II mutations alone, or in any combination, or any of the 12 site III mutations alone, or in any combination. The claims would also encompass any combination of the 16 site II and 12 site III mutations. Thus, the claims could potentially encompass millions of different G-CSF and GCSRR variant pairs with different combinations and subcombinations of mutations. The claims require that the variant G-CSF binds the receptor preferentially over a wild type G-CSFR ECD, and that the receptor binds the variant G-CSF preferentially over a wild type G-CSF.
The state of the art is such that protein chemistry is one of the most unpredictable areas of biotechnology. Whisstock et al (Quarterly Review of Biophysics, 2003, 36, pp307-340) teach that the prediction of protein function from sequence and structure is a difficult problem, because homologous proteins often have different functions. Even single amino acid changes in a proteins amino acid sequence can have dramatic effects on protein function. For example, Wang et al. , 2001, show that a single amino acid determines lysophospholipid specificity of the S1P1 (EDG1) and LPA1 (EDG2) phospholipids growth factor receptors (e.g., abstract). These references demonstrate that even a single amino acid substitution or what appears to be an inconsequential chemical modification will often dramatically affect the biological activity and characteristic of a protein.
The specification discloses that G-CSF of SEQ ID NO: 1 and ECD of G-CSFR of SEQ ID NO: 2 with certain specific paired mutations that can function as claimed. The specification in Table 7 discloses 13 embodiments that function as claimed. For example, in Table 7 design 130 represent a particular embodiment of a variant G-CSF having SEQ ID NO: 1, with E46R, L108K and D112R mutations, paired with a variant ECD of SEQ ID NO: 2, with R41E and R167D mutations (see Table 6 which defines each design). However, these species are not sufficiently representative of the broad genus of different variants encompassed by the instant claims. Regarding claim 77, it is noted that this would still encompass up to 45 other mutations (including substitution, additions or deletions) because of the least 85% identity language of claim 32, from which the claim depends. The specification provides no guidance regarding what other changes could be made while maintaining the claimed function . The specification discloses that the variants were identified by a process involving making mutation combinations and testing for the claimed function. However, this trial and error process does not provide any information as to the actual structure of a variant that would have the claimed function. The application at best describes a roadmap for producing candidate variant polypeptides, and then determining which actually exhibit the claimed activity. See Novozymes A/S v. DuPont Nutrition Biosciences. 107 USPQ2d 1457 (Fed. Cir. 2013). In Novozymes the court held that the problem is that “the specification failed to inform the reader which member of that group was the right one.” Accordingly, because “[t]he actual inventive work of producing a [working variant] was left for subsequent inventors to complete,” the application provided insufficient written description for the claims.
The instant application has not provided a sufficient description showing possession of the necessary functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus of variants. Further, the Court has interpreted 35 U.S.C. §112, first paragraph, to require the patent specification to “describe the claimed invention so that one skilled in the art can recognize what is claimed. Enzo Biochem, Inc. v. Gen-Probe Inc, 63 USPQ2d 1609 and 1618 (Fed. Cir. 2002).
In evaluating whether a patentee has fulfilled this requirement, our standard is that the patent’s “disclosure must allow one skilled in the art ‘to visualize or recognize the identity of’ the subject matter purportedly described.” Id. (quoting Regents of Univ. of Cal. v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed Cir. 1997)).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear 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.)
Also, it is noted that the Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See University of Rochester v. G.D. Searle & Co., lnc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004). Thus, one of skill in the art would conclude that the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus. See Eli Lilly, 119 F. 3d 1559, 43, USPQ2d 1398.
Applicant argues that the amendment overcomes the rejection. However, the claims are rejected for the reasons set forth above.
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.
Claim 32, 76-77, and 90-93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 306 of copending Application No. 18/286,045 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘045 application claims a system comprising a variant G-CSF and a receptor comprising a variant ECD of G-CSFR, wherein the variant G-CSF binds selectively to a receptor comprising a variant ECD of G-CSFR (i.e. binds preferentially over wild-type), and wherein the variant G-CSF and receptor comprising at least one mutation in a site II interface region and a site III interface region. The ‘045 application further claims that variant G-CSF comprises E46R, L108K and D112R, mutations, and that the variant G-CSFR ECD comprises R41E and R167D mutations.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicants attempt that the rejection be held in abeyance until allowance is acknowledged.
The following is a new ground of rejection necessitated by Applicant’s claim amendments.
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 32, 76-77, 90-93 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.
Claim 32 is indefinite in the recitation that the variant G-CSFR or variant G-SCF comprises a sequence having at least 85% identity to SEQ ID NO: 2 or SEQ ID NO: 1, “expect” wherein the variant comprises at least one mutation selected from the recited groupings. A claim directed to a variant G-CSF comprising SEQ ID NO: 1, except for at least one mutation, for example, would be clear. This would be interpreted as requiring all of SEQ ID NO: 1 expect for the specified mutations. However, the combination of the at least 85% identity language with “except” wherein the variant comprises the specified mutations renders the claims indefinite. It is unclear whether the claims would encompass variants with less than 85% identify, if the variants that cause less than 85% identity were selected from the recited mutations. Or do the claims require that the variants have at least 85% identity to SEQ ID Nos: 1 and 2 including the one or more substituted positions required in the instant claims. For example, SEQ ID NO: 2 is 307 amino acids in length, and one could vary 46 positions outside of the recited positions in the claims to arrive at a polypeptide having 85% identity (i.e. 261/307 positions that are identical). Would the claims encompass making 20 other changes to said 85% identical variant selected from the specific site II and site III positions recited in claim 32? This would then have 241/307 positions in common, wherein 20 of the variant positions are selected from the recited positions and 46 are elsewhere, but would overall be 78% identical to SEQ ID NO: 2. Or would the claims require that the sum of all variant positions, including those specifically recited, needs to result in a variant G-SCFR at least 85% identical to SEQ ID NO: 2. The scope of the claims is unclear and indefinite. For the purposes of examination, the claim is being interpreted as requiring a least one of the recited substitutions, and an overall 85% identity to the recited SEQ ID Nos:. Amendment to remove the “except” language would be remedial in the context of the 85% identity. Alternatively, Applicant could amend claim 32 to remove the “at least 85% identity” language to overcome the rejection. For example, a variant G-CSFR comprising SEQ ID NO: 2 “except” wherein it comprises at least one mutation selected from the recited group would also be clear and definite.
No claim is allowed.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644