Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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 claim amendments filed 8/5/25. Claims 18-19, 22-24, 29-40, 43-45, 47, 56, and 63-70 are pending and under examination.
Notice
The examiner in charge of your application in the USPTO has changed. To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to SPE Adam Weidner of Art Unit 1651.
Withdrawn Rejections
The rejection under §101 is withdrawn.
The rejections under §112(b) are withdrawn.
The enablement rejection is withdrawn.
The written description is withdrawn in part. The maintained portion of the rejection is set forth below.
Claim Objections
Claims 44 and 65-69 are objected to because of the following informalities:
Only one period is allowed in a claim except for when used with abbreviations (MPEP §608.01(m)).
Claim 44 subsection (g) recites “SEQ ID NO: 478., and”, where the number “478” does not appear to be an abbreviation and so should not be accompanied by a period.
Further, claims 18-19, 22-24, 29-40, 43-45, 47, 56, and 63-64 recite “SEQ ID NO:”, using a colon. New claims 65-69 utilize “SEQ ID NO.”, with a period. While “No.” is an abbreviation of “number” and so the period is acceptable (see MPEP §2422 for explicit indication that this format is acceptable), referring to SEQ ID NOs should nevertheless be consistent between claims. While the Examiner suggests using the colon throughout (MPEP §2422 also indicates this is the preferred phrasing), using the period throughout is also acceptable. However, the same format should be used throughout the claims.
Appropriate correction is required.
Claim 47 is objected to because of the following informalities: part (e) states “bone or cancer” which appears to be a misspelling of “bone cancer”.
Appropriate correction is required.
Claims 24 and 44 are objected to because of the following informalities: Claim 18 has been amended to indicate that the CD3e and PMSA are both human and primate. The claim has also been amended to make clear that the CDRs are those of the PMSA binding domain. Claim 24 depends from claim 18 and so should include similar changes, i.e., clearly indicating the amino acid sequences are for the PMSA portion of the antibody. While not directly dependent on claim 18, the antibodies of claim 44 appear to be the same antibodies and so should also contain similar language.
Appropriate correction is required.
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 18-19, 22-24, 29-40, 43-45, 47, 56, and 63-68, 70 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.
The issue of a lack of written description may arise when the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process. This position is consistent with court decisions and with further regard to the proposition that, as original claims, the claims themselves provide in haec verba support sufficient to satisfy the written description requirement, the Federal Circuit has explained that in jpsis verbis support for the claims in the specification does not per se establish compliance with the written description requirement:
Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement. The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997). See also: University of Rochester v. G.D. Searle & Co., 69 USPQ2d 1886 1892 (CA FC 2004).
Thus, an original claim may provide written description for itself, but it must still be an adequate written description, which establishes that the inventor was in possession of the invention.
In this instance, the claims are drawn to a bispecific single chain antibody, which comprises a CD3e binding domain, which must function to bind to a CD3e polypeptide, and a PSMA binding domain, which must function to bind to a PSMA polypeptide. As amended, claim 18 requires the six CDRs for the PMSA binding domain that define/correlate to the function of binding PMSA. The antibody comprises, for example, a “CDR- L1 comprising the amino acid sequence of SEQ ID NO: 269”, a “CDR-L2 comprising the amino acid sequence of SEQ ID NO: 270’, a “CDR-L3 comprising the amino acid sequence of SEQ ID NO: 271”, a “CDR-H1 comprising the amino acid sequence of SEQ ID NO: 274’, a “CDR-H2 comprising the amino acid sequence of SEQ ID NO: 275”, and a “CDR-H3 comprising the amino acid sequence of SEQ ID NO: 276”. As amended, it is now clear that these CDRs represent the PMSA binding portion of the antibody. However, this means that the CD3 epsilon binding portion remains undefined by any relevant structure.
Applicant is reminded that “generalized language may not suffice if it does not convey the detailed identity of an invention.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1892 (CAFC 2004). A description of what a material does, or must be capable of doing, rather than of what it is, does not suffice to describe the claimed invention (emphasis added).
In general, due to structural differences, it must be determined by empirical examination whether any given antibody such as that to which claim 18 is drawn is an antibody that is capable of binding to both human and primate “CD3e” polypeptide. The Federal Circuit has decided that 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 Noelle v. Lederman, 69 USPQ2d 1508 1514 (CA FC 2004) (citing Enzo Biochem II, 323 F.3d at 965; Regents, 119 F.3d at 1568).
Supporting the position taken herein, there is no way to a priori look at an antigen sequence (CD3e) and envisage the combination of six CDRs that will bind that antigen. Even when provided with several related antibodies that bind the desired target, this does not represent the astronomical and potentially unknowable breadth of all possible amino acid sequences which will result in the desired binding properties. This is exemplified by the Court decision in Abbvie (Abbvie v Janssen 759 F.3d 1285 (Fed. Cir. 2014)), where Abbvie developed over 200 antibodies that shared 99.5% identity in the variable regions (p.7) and which bound the target, but in no way allowed one to envisage the unique structure of Centocor' s antibodies which bound the same target but shared only 50% sequence similarity (see table on page 11).
Applicant has disclosed three combinations of three CDRs on the light chain which define binding to CD3e (claim 65), yet this does not allow the skilled artisan to envisage even a single other combination of CDRs which would predictably have the same binding properties.
“As this court has repeatedly stated, the purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.’ Rochester, 358 F.3d at 920 (quoting Reiffin v. Microsoft Corp., 214 F.3d 1342, 1345 (Fed. Cir. 2000)). It is part of the quid pro quo of the patent grant and ensures that the public receives a meaningful disclosure in exchange for being excluded from practicing an invention for a period of time. Enzo, 323 F.3d at 970.” Id. 598 F.3d at 1353-1354.
In conclusion, it is submitted that in this case, since the claims are so broad (all possible sequences which bind both human and primate CD3e), and the disclosure is so comparably limited (three combinations of light chain CDRs and 10 combinations of heavy chain CDRs), any alleged conception has no more specificity than simply a wish to know the identity of any material with the requisite biological properties, which can be used to practice the claimed processes, so as to achieve the claimed objectives or effects. In such instances, the alleged conception fails not merely because the field is unpredictable or because of the general uncertainty surrounding experimental sciences, but because the conception is incomplete due to factual uncertainty that undermines the specificity of the inventor’s idea of the invention. Burroughs Wellcome Co. v. Barr Laboratories Inc., 40 F.3d 1223, 1229, 32 USPQ2d 1915, 1920 (Fed. Cir. 1994). Since the claims are not necessarily limited to known materials having the properties of the claimed “bispecific single chain antibody”, but rather to such material that might be identified, given the bid set forth in the instant disclosure to do so, it is noted that one cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481, 1483 (Bd. Pat. App. & Int. 1993).
Newly added claims 65 and 67 define the light chain while claims 66 and 68 define the heavy chain. However, three CDRs are insufficient to define the binding properties of antibodies. It is well-known in the art that specificity of an antibody stems from the interaction of six CDRs and CDRs are not generally recognized as interchangeable, such that using three CDRs from one antibody would not be reasonably expected to confer the same binding properties or even the same binding target when combined with three CDRs from other antibodies. For example, WO 2008068048 (cited on form 892) discloses an antibody with a heavy chain comprising three CDRs (SEQ ID NO: 2) that binds secreted aspartyl protease from Candida sp. US 20170355756 (form 892) describes the same three CDRs in the heavy chain (C10-VH3) combined with a different light chain that binds human TDP-43. There is no evidence in the instant specification that defining only the light chain or only the heavy chain CDRs is sufficient to conserve the required binding properties. As such, the specification fails to set forth a structure-function correlation sufficient to claim all possible antibodies defined by function and three CDRs.
Therefore, claims 18-19, 22-24, 29-40, 43-45, 47, 56, and 63-68, 70 do not meet the written description requirement.
Allowable Subject Matter
Claim 69 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Claim 69 defines all six CDRs of the PMSA binding portion (due to dependence on claim 18) as well as the six CDRs of the CD3e binding portion, sufficient to describe the structure associated with the claimed functions. Note that combining claims 65 and 66—including their dependence on claim 18—represents sufficient written description for the antibody as a whole.
Response to Arguments
Applicant's arguments filed 8/5/25 have been fully considered but they are not persuasive.
Regarding the written description rejection, Applicant argues that claim 18 now defines all six CDRs as specifically those of the PMSA binding region and that it is clarified this is human or primate PMSA. While this is persuasive for the PMSA binding region, it does not address the lack of adequate structure for the CD3e binding region. As stated in the previous rejection, the written description rejection used PMSA as an example for discussion of the deficiencies (p.17 “nevertheless, as an example”). While the rejection used PMSA to exemplify the issue, the deficiencies noted therein applied equally to the CD3e portion. The rejection herein has been amended solely to discuss the CD3e portion explicitly (now that the PMSA deficiency no longer exists) and to address the new limitations where only three of the six CDRs are defined. Thus, while Applicant persuasively argues “it is indeed clear which ‘PMSA’ polypeptides are bound by the antibody having the structural features recited by the claims” (remarks 8/5/25 p.19), it remains that there are no such structural features for the CD3e portion recited by the claims.
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-F 9-16.
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/Adam Weidner/ SPE, Art Unit 1651