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 .
Status of Claims
Claims 1, 10-11, 13-31, and 34 are pending as of the response and amendments filed on 4/1/26. Claims 2-9, 12, and 32-33 have been canceled. Claims 19-29 are currently withdrawn from examination as being drawn to a non-elected invention. Claims 1, 10-11, 13-18, 30-31, and 34 are currently under examination.
Applicant’s arguments in response to the rejection under 35 USC 112(a) for lack of written description are summarized and addressed below.
Applicant has described the claimed invention as a technology platform for covalently and reversibly conjugating protein drug moieties to polymeric moieties to improve their pharmacokinetic properties without the need for an amide protecting group. Applicant has further discussed how amide protecting groups were previously required in the art to avoid early and undesired drug release during synthesis, and that the linker moiety -L1- of formula (I-a) of claim 1 as amended covalently and reversibly connects -D to a carrier moiety Z without the need for amide protecting groups. Applicant has further argued the example protein drug moieties of the disclosure merely serve as model moieties that can be exchanged for different protein drug moieties without requiring undue experimentation.
Applicant’s arguments have been fully considered but are not found fully persuasive. While the amendments to the claims and discussion of the background of the invention are greatly appreciated, it is noted that the claims recite the conjugated to be composed of “at least one moiety -D” conjugated to “at least one moiety” -L1-L2- to “at least one moiety” Z. As such, there is no limit to the number of moieties D, -L1-L2-, and Z of the claimed conjugates, encompassing an endless number of such moieties. As discussed in the previous office action, if a claimed genus has a substantial variance, the disclosure must describe a sufficient variety of species to demonstrate written description. Applicant’s specification only describes conjugate species consisting of a single protein moiety D conjugated to a single moiety -L1-L2- to a single moiety Z; see Exs. 2b, 15b, 21, and 32 in specification. Additionally, the synthetic schemes present in the specification only describe making conjugates formed by a single protein moiety D conjugated to a single moiety -L1-L2- to a single moiety Z. Therefore, Applicant doesn’t have adequate written description for the claimed conjugates, which can be composed of any number of moieties D conjugated to an endless number of moieties -L1-L2-, to any number of moieties Z. One of ordinary skill in the art would have to practice undue experimentation to determine how to make conjugates composed of potentially hundreds or thousands of protein moieties D, conjugated to any number of moieties -L1-L2- to any number of moieties Z. It is maintained that the specification does not reflect a sufficient variety of the claimed species to demonstrate written description of the claimed conjugates. To overcome this rejection, it is suggested the claims be amended to reflect a conjugate composed of a single moiety -D conjugated via a single moiety -L1-L2- to a single moiety Z. While the rejection over claim 34 with respect to lack of written description for treating or preventing a disease is withdrawn, the lack of written description over this claim is still maintained as this claim requires administering a conjugate of claim 1, and claim 1 remains rejected for the reasons discussed above.
The rejection of claims 1-18, 30-31, and 34 under 35 USC 112(b) is withdrawn in consideration of the amendments and Applicant’s remarks. However, a new rejection under 35 USC 112(b) is made over claim 30 based on amendments, discussed below.
Claims 1, 10-11, 13-18, 30-31, and 34 were examined and are rejected.
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.
Claim 1, 10-11, 13-18, 30-31, and 34 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.
Independent claim 1 is drawn to a conjugate comprised of a moiety comprising at least one moiety -D conjugated via at least one moiety -L1-L2- to at least one moiety Z, with -D defined as a primary or secondary amine containing moiety of a drug D-H. The conjugate of claim 1 encompasses potentially millions of drugs that meet D-H, encompassing any protein drug moieties. The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated:
“To fulfill the written description requirement, a patent specification must
describe an invention and do so in sufficient detail that one skilled in the art can
clearly conclude that "the inventor invented the claimed invention." Lockwood
v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In
re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he
description must clearly allow persons of ordinary skill in the art to recognize
that [the inventor] invented what is claimed."). Thus, an applicant complies with
the written description requirement "by describing the invention, with all its
claimed limitations, not that which makes it obvious," and by using "such
descriptive means as words, structures, figures, diagrams, formulas, etc., that
set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at
1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398”.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” See MPEP 2163.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co., the court stated: “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus... ."). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398”. The MPEP 2163 does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. Although the MPEP does not define what constitute a sufficient number of representatives, the Courts have indicated what doesn’t constitute a representative number of species to adequately describe a broad genus. The originally filed disclosure discloses conjugate species wherein -D represents ubiquitin or the protein HHCMET, but there is no description of conjugates having -D represented by the millions of other potential proteins. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). For these reasons, the claimed invention lacks written description. The claim(s) contains subject matter which was not described in the specification and the few examples do not constitute a representative number species to adequately describe a broad generic. In Gostelli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618. For written description, the analysis (a) considers actual reduction to practice, (b) disclosure of drawing or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties, functional characteristics when coupled with known or disclosed and (d) Representative number of examples.
(a) Actual reduction to practice/ (b) Disclosure of drawing or structural chemical formulas:
The originally filed disclosure discloses example conjugates wherein -D is ubiquitin or the protein HHCMET.
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties, functional characteristics when coupled with known or disclosed:
The claims are drawn to conjugates composed of a protein drug -DH conjugated to at least one moiety -L1-L2 to at least one moiety Z which broadly discloses the structures, in generic structural terms; for instance, -D is defined as any primary or secondary amine or any protein drug -DH; L2 is any spacer moiety or a single bond; and Z is any polymer moiety or a C8-24 alkyl.
(d) Representative number of examples:
The MPEP states that a broad genus can be described by a showing of representative number of examples. The claims in the instant application are broad. In the instant case, the conjugate encompasses at least one protein moiety -D conjugated via at least one moiety -L1-L2- to at least one moiety -Z, wherein -D is any primary or secondary amine of any protein drug -DH; -L1- is defined by formula (I-a); -L2- is a single bond or spacer moiety; and Z is any polymeric moiety or a C8-24 alkyl. However, the specification fails to provide a representative number of examples for these. The specification provides a few examples of conjugates wherein -D is ubiquitin or the protein HHCMET. Additionally, the conjugates described in the specification are composed of limited species for -L1-L2- and Z, as shown:
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. No other examples or description of conjugates wherein -D is anything other than ubiquitin or HHCMET are provided. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). For these reasons, the claimed invention lacks written description. The claim(s) contains subject matter which was not described in the specification in such a way to reasonably convey to one of ordinary skill in the art that the inventor, at the time the application was filed, had possession of the claimed invention. Claims 10-11, 13-18, 30-31, and 34 are similarly rejected as these claims depend from claim 1.
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.
Claim 30 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 30 as amended refers to attachment of a linker of formula (II) at the dashed line to -Q, however, -Q is not defined by the claim.
Claim 30 also refers to a linker of formula (I) in step (c), however, formula (I) is not defined within the claim, and amended claim 1 no longer recites formula (I). Therefore, the metes and bounds are unclear, and the claim is indefinite.
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.
Information Disclosure Statement
The IDS filed on 4/1/26 has been considered.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH PIHONAK whose telephone number is (571)270-7710. The examiner can normally be reached Monday-Friday 9:00-5:30 EST.
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SARAH . PIHONAK
Primary Examiner
Art Unit 1627
/SARAH PIHONAK/ Primary Examiner, Art Unit 1627
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