Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Claim Status
2. This Office Action is in response to the amendment filed 20 October 2023, wherein Applicant amended claims 2-11 and added new claims 12-14.
Claims 1-14 are under consideration.
Information Disclosure Statement
3. The information disclosure statement (IDS) submitted on 20 October 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the Examiner.
Specification
4. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http://, www., or other browser-executable code. See MPEP § 608.01.
See page 5 of the Instant Specification.
5. The use of the terms “CERVARIX”, “PROVENGE”, “FLUBLOK”, and “TAQMAN” on page 1 of the Instant Specification, which are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Note that “CERVARIX”, “PROVENGE”, “FLUBLOK”, and “TAQMAN” are merely examples and all improper uses of trademarks in the specification should be identified by Applicant and properly addressed.
Claim Objections
6. Claims 1, 4-6, 8, and 10-11 are objected to because of the following informalities:
Regarding claim 1, acronyms should be spelled out when initially used. “CCTCC“ should be spelled out.
Regarding claims 4-6, 8, and 10-11, a comma (Oxford comma) should be added before “and” in a list for clarity.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
7. 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.
8. Claim 9 is 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 9 contains the trademark/trade name “nanobody”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe an antibody and, accordingly, the identification/description is indefinite.
9. 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.
10. Claims 2-4 and 8 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.
When establishing a 35 U.S.C. 112(a) written description rejection, the burden is on the Examiner to set forth a prima facie case providing reasons why the specification is deficient and thus the
claims that relies thereon are rejected. It is important to note that each claim is given its broadest
reasonable interpretation in light of and consistent with the written description (see MPEP 2111 and
2163(II)). Additionally, a full review of the application must be done to understand how the applicant
provides support for the claimed invention during each element and/or step, which includes the
specification, drawings, structural chemical formulas, etc. (see MPEP 2163(II)). Finally, a determination
as to whether the applicant was in possession of the claimed invention at the time of filing is made by
considering (see MPEP 2163(II)):
1) The variety of ways that that applicant may show possession,
2) The level of skill and knowledge in the art, and
3) The predictability in the art.
Each of the claims are drawn, either inherently or explicitly, to the possession of an antibody that is produced by a method involving the insect cell WSK-Sf9. Claim 2 recites “expressing the recombinant protein”, which includes antibodies; claim 3 recites “wherein the composition is a medicine”; claim 4 recites, “wherein the medicine comprises…an antibody”; and claim 8 recites, “an antibody selected from the group consisting of a monoclonal antibody, a Fab antibody, a scFv antibody and a nanobody”. Other than a prophetic statement, the specification does not provide a method of making a composition with an antibody, nor does it define any antibodies that can be used. Additionally, the supplemental information (e.g. the drawings), do not provide any indication of antibodies.
At the time of filing, antibodies must be defined by their set of six CDRs or a VL and VH framework, otherwise they are unpredictable in the art. See the enablement rejection below for the state of the prior art.
In support of the claimed genus of an “an antibody” The specification discloses no specific antibody. Furthermore, no derivatives or variants or mutants thereof are disclosed. Thus, the application fails to provide examples of any species within the claimed genus.
Moreover, the decision arrived at in Amgen v. Sanofi, 598 U.S. 594 (2023) supports expanded analysis of whether a claim drawn to an antibody being specific for an epitope, even a specific epitope, permits an applicant to pursue all possible antibodies that are capable of being produced against such an epitope. Presently, the claimed antibody is not defined by any functional properties. In view of the fact patterns detailed in Amgen v. Sanofi, applicants are not in possession of a method that produces an antibody.
In view of the fact that the examples provided do not demonstrate possession of an antibody, the application has not identified an antibody, and one of ordinary skill in the art at the time of filing would not have recognized the possession of an antibody, there is insufficient written description support for a composition comprising an antibody.
11. Claims 1-14 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The claims are drawn to a Rhabdovirus-negative Spodoptera frugiperda insect cell line WSK-Sf9 that has been deposited with the accession number C202246. However, not all statements or declarations have been provided as described below related to the Budapest Treaty and that all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of a patent. Furthermore, the specification does not recite any deposit information as detailed in the MPEP under 37 CFR 1.809(d). In addition, the biological deposit form filed on 20 October 2023 does not have an English translation.
It is apparent that C202246 is required to practice the claimed invention because it is a necessary limitation for the success of the invention as stated in the claims. As a required element it must be known and readily available to the public or obtainable by a repeatable method set forth in the specification, or otherwise readily available to the public. If it is not so obtainable or available, the enablement requirements of 35 U.S.C. § 112, first paragraph, may be satisfied by a deposit of C202246. See 37 CFR 1.802. One cannot practice the claimed invention without this specific cell line. One cannot determine whether a cell line has the necessary characteristics without access to C202246. Therefore, access to C202246 is required to practice the invention. The specification does not provide a repeatable method for C202246 without access to the ThermoFisher Sf9 cell line with the specific lot number 2043331, and it does not appear to be readily available material.
Deposit of C202246 in a recognized deposit facility would satisfy the enablement requirements of 35 U.S.C. 112., because the strains would be readily available to the public to practice the invention claimed, see 37 CFR 1.801- 37 CFR 1.809.
If a deposit is made under the terms of the Budapest Treaty, then an affidavit or declaration by applicants or someone associated with the patent owner who is in a position to make such assurances, or a statement by an attorney of record over his or her signature, stating that the deposit has been made under the terms of the Budapest Treaty and that all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of a patent, would satisfy the deposit requirements. See 37 CFR 1.808.
If a deposit is not made under the terms of the Budapest Treaty, then an affidavit or declaration by applicants or someone associated with the patent owner who is in a position to make such assurances, or a statement by an attorney of record over his or her signature, stating that the deposit has been made at an acceptable depository and that the following criteria have been met:
(a) during the pendency of this application, access to the invention will be afforded to one determined by the Commissioner to be entitled thereto;
(b) all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon granting of the patent;
(c) the deposit will be maintained for a term of at least thirty (30) years and at least five (5) years after the most recent request for the furnishing of a sample of the deposited material;
(d) a viability statement in accordance with the provisions of 37 CFR 1.807; and
(e) the deposit will be replaced should it become necessary due to inviability, contamination or loss of capability to function in the manner described in the specification.
In addition, the identifying information set forth in 37 CFR 1.809(d) should be added to the specification. See 37 CFR 1.803 - 37 CFR 1.809 for additional explanation of these requirements.
Applicant has already deposited the material in a recognized facility and identified the date, location, and materials deposited in the Instant Specification. However, Applicant is missing declarations as listed above.
12. Claims 2-4 and 8 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 method of producing cytokines, hormones, or a recombinant enzyme, does not reasonably provide enablement for a method of producing an antibody. 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.
With respect to claims 2-4 and 8, in making a determination as to whether an application has met the requirements for enablement under 35 U.S.C. 112 ¶ 1, the courts have put forth a series of factors. See, In re Wands, 8 USPQ2d 1400, at 1404 (CAFC 1988). The factors considered include: (1) the breadth of the claims, (2) the nature of the invention, (3) the relative skill of those in the art, (4) the presence of absence of working examples, (5) the amount of direction or guidance provided, (6) the state of the prior art, (7) the level of predictability in the art, and (8) the quantity of experimentation necessary.
1) The claims are drawn to a composition that can include an antibody; this antibody can include polyclonal antibodies in addition to the defined monoclonal, Fab, scFv, or nanobody. It could also read on full length or truncated/mutated CDRs.
2) The nature of the invention a recombinant protein expressed by a Rhabdovirus-negative Spodoptera frugiperda insect cell line WSK-Sf9 with a CCTCC accession number C202246.
3) The relative skill of those in the art is high.
4) The specification provides no working examples for any antibodies.
5) The specification provides no direction or guidance for using the cell line to create a medicine with antibodies.
6-8) The state of the prior art is such that it is well established in the art that the formation of an intact antigen-binding site of antibodies generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope (Paul, Fundamental Immunology, 1993, 3: 292-295, under the heading “Fv Structure and Diversity in Three Dimensions”) (See PTO-892: Notice of References Cited). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (Paul, page 293, first column, lines 3-8 and line 31 to column 2, line 9 and lines 27-30).
Additionally, Bendig (Methods: A Companion to Methods in Enzymology, 1995, 8: 83-93) (See PTO-892: Notice of References Cited) reviews that the general strategy for “humanizing” antibodies involves the substitution of all six CDRs from a rodent antibody that binds an antigen of interest, and that all six CDRs are involved in antigen binding (see entire document, but especially Figures 1-3). It is noted that Bendig used Kabat CDRs in their humanization process (Page. 86, Column 2, ¶ 2). Similarly, the skilled artisan recognized a “chimeric” antibody to be an antibody in which both the heavy chain variable region (which comprises the three heavy chain CDRs) and the light chain variable region (which comprises the three light chain CDRs) of a rodent antibody are recombined with constant region sequences from a human antibody of a desired isotype (see entire document, but especially Figures 1-3).
Thus, the state of the art recognized that it would be highly unpredictable that a specific antibody comprising less than all six parental CDRs would have antigen binding function. The minimal structure which the skilled artisan would consider predictive of the function of binding the antigen of a murine or humanized antibody includes six CDRs (three from the heavy chain variable region and three from the light chain variable region) in the context of framework sequences which maintain their correct spatial orientation and have the requisite binding function. One of skill in the art would neither expect nor predict the appropriate functioning of the antibody fragments and mutated antibodies of the instant claims as broadly as claimed.
In the case of antibodies, it is especially important to disclose which residues are permissive to mutation. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff (Proc. Natl. Acad. Sci. USA, 1982, 79: 1979-1983) (See PTO-892: Notice of References Cited). Rudikoff teaches that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function (Abstract).
Therefore, it is impossible to know, absent further undue experimentation, the combination of CDRs or VL/VH frameworks that will work in a medicine. Any modifications (mutations/truncations) will also be unpredictable in function, when, as set forth above, even a single change of an encoded amino acid can unpredictably affect antibody structure and function, leads to one having no predictability or expectation of success for the function of any given antibody modification. Such random experimentation to identify at a later time what structure or fragment or modification is or is not functional and is embraced by Applicant’s claims is undue experimentation.
Moreover, claims not containing elements critical or essential to the practice of the invention, such as antibodies or antibody fragments not having all of the relevant functional complementarity determining regions (CDRs) in the proper site on an appropriate antibody heavy or light chain framework, are not enabled by the disclosure. See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976). Note that an enabling disclosure for the preparation and use of only a few analogs of a product does not enable all possible analogs where the characteristics of the analogs are unpredictable. See Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ 2d 1027 (CAFC 1991).
In view of the lack of the predictability of the art to which the invention pertains as evidenced by the art above, the lack of guidance and direction provided by applicant, and the absence of working examples, undue experimentation would be required to make and use functional antibody molecules comprising fewer than all six complete parental CDRs with a reasonable expectation of success, absent a specific and detailed description in applicant’s specification of how to effectively practice this and absent working examples providing evidence which is reasonably predictive that the claimed antibodies are functional, commensurate in scope with the claimed invention.
Allowable Subject Matter
13. The following is a statement of reasons for the indication of allowable subject matter: the closest prior art is Maghodia (Protein Expr. Purif., July 2016, 122: 45-55) (See IDS filed 20 October 2023) that teaches a Sf9 cell line that is rhabdovirus-negative. However, Maghodia does not teach that the cell is WSK-Sf9, which was derived from the ThermoFisher Sf9 cell line with the specific lot number 2043331.
Therefore, a Rhabdovirus-negative Spodoptera frugiperda insect cell line WSK-Sf9 that has been deposited with the accession number C202246 is free of the prior art of record.
Conclusion
14. No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA E LY whose telephone number is (571)272-5169. The examiner can normally be reached Monday - Thursday, 8:00 am - 5:00 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached at (571) 270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KRISTINA E. LY/Examiner, Art Unit 1671
/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671