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 .
Response to Amendment
Applicant's response filed 31 March 2025 has been received and entered. Claims 7, 18, 25-27, 34 and 51-53 have been amended and claims 3-5, 8-10, 13, 15-16, 20, 23, 30-32, 35-37, 40, 42-46, 49, 60 and 62-63 have been canceled. Claims 1-2, 6-7, 11-12, 14, 17-19, 21-22, 24-29, 33-34, 38-39, 41, 47-48, 50-59 and 61 are currently pending and under consideration in the instant Office action.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Any objection or rejection of record which is not expressly repeated in this action has been overcome by Applicant's response and withdrawn.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-2, 6-7, 11-12, 14, 17-19, 21-22, 24-29, 33-34, 38-39, 41, 47-48, 50-59 and 61 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statements (IDS) submitted on 31 March 2025, 28 August 2025, 25 March 2026 and 13 July 2026 have been considered by the examiner.
Drawings
The drawings are objected to because they do not comply with 37 CFR 1.84(a)(1) (India ink, or its equivalent that secures solid black lines, must be used for drawings) and 1.84(l) (every line, number, and letter must be durable, clean, black, sufficiently dense and dark, and uniformly thick and well defined). For example, Figure 5 has features which are not clear due to lack of black ink. Understanding the features in the figures is necessary for understanding the invention (components). Additionally, the text and lines of the figures appear blurry because the lines are not solid, as required.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The use of the term VELOCIMMUNE® (see page 19), which is a trade name or a mark 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.
The use of the term TWEEN®20 (see [0082]), which is a trade name or a mark 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.
The use of the term HELEOS® (see [0305]), which is a trade name or a mark 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.
The use of the term Optilab® (see [0305]), which is a trade name or a mark 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.
The use of the term Expi293F™cells (see [0315]), which is a trade name or a mark 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. (NOTE: Expi293F appears in the very next line and does not include the proper symbol).
Applicant should review the specification for other instances of trademarks (see at least [0325]).
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.
The disclosure is objected to because of the following informalities:
Table 1A at page 20 of the specification makes reference to FGFR1c antibodies and includes information regarding the amino acid sequences of the referenced antibodies. While the table recites “Sequence in Patent Reference”, the mention of sequence identifiers with the “Seq ID NO.” notation can cause confusion between the sequences being referenced from a different source and the actual sequences and sequence identifiers in the instant specification. This actually may cause confusion with the printer if the instant application matures into a patent. It is suggested that instead of using the notation necessary for Sequence compliance, “Seq ID NO.” could be replaced with the generic term “sequence” along with the number. The same issue is also found in Tables 2A and 3A. Paragraph [0162] also references sequences from other sources using the sequence identifier format. Again, it might be advisable to use a different format for referencing the sequence other than “SEQ ID NO:” to avoid confusion with the sequences in the instant application. See also [0167], [0206], [0207] and Table 5
Appropriate correction is required.
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 1-2, 6, 19, 21-22, 24-29, 33, 47-59 and 61 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 instant claims are directed to a multispecific binding molecule (MBM), methods of administering such, nucleic acid encoding such and methods of producing such. Claims 1 and 28 recite that the MBM comprises 3 antigen-binding modules which specifically bind to 3 different targets; FGFR1c, GH1 domain of KLB and GH2 domain of KLB.
The instant specification discloses trispecific binding constructs which are based on antibodies and antibody structures. The specification disclosure is limited to specific structures which comprise a bispecific antibody wherein an scFv is attached to the antibody or an Fab is attached to the antibody. The instant specification does not describe any other types of molecules which might be encompassed by the generic recitation of “multispecific binding molecule” nor does it describe any other types of structures which will bind all three targets in a coordinated fashion and result in a molecule that mimics FGF21 and functions to activate FGFR1c/KLB. “Binding molecule” is not limited to antibodies and the instant specification only describes antibody molecules which will function in the “multispecific binding molecule”. In order to use the claimed invention, the MBM will need to function in the manner disclosed in the specification and the only structures which are disclosed which will perform in the manner required are antibody constructs. Chemical molecules can bind proteins; aptamers can bind proteins; receptor molecules can bind proteins; however, the instant specification fails to provide an adequate written description for any binding molecules which are not antibodies and also fails to provide a multispecific binding molecule which does not have the structure of a bispecific antibody linked to an scFv or an Fab (see structures in Figures 6A and 8B).
The structures of the MBM’s of the claims are not adequately described. In AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., Ill USPQ2d 1780 (Fed. Cir. 2014) AbbVie had claims to functionally claimed antibodies and Centocor presented evidence that the antibodies described in AbbVie's patents were not representative of other members of the functionally claimed genus. The decision states, “When a patent claims a genus using functional language to define a desired result, ‘the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus.’ Id. at 1349. We have held that 'a sufficient description of a genus ... requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can “visualize or recognize” the members of the genus.’ Id. at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). Here, the claimed invention is a class of fully human antibodies that are defined by their high affinity and neutralizing activity to human IL-12, a known antigen. AbbVie's expert conceded that the '128 and '485 patents do not disclose structural features common to the members of the claimed genus.”
The AbbVie decision considers how large of a genus is involved and what species of the genus are described in the patent. With the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus. See Ariad, 598 F.3d at 1353 (The written description requirement guards against claims that “merely recite a description of the problem to be solved while claiming all solutions to it and ... cover any compound later actually invented and determined to fall within the claim's functional boundaries.”).
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing 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.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B(1), the court states, “An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.”
Thus, given the level of skill and knowledge and predictability in the art, those of skill in the art would not conclude that the applicant was in possession of the claimed genera of MBMs based on disclosures set forth above. "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004). For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly.
In the absence of sufficient recitation of distinguishing characteristics, the specification does not provide adequate written description of the claimed genus, which are MBMs comprising 3 antigen-binding modules. One of skill in the art would not recognize from the disclosure that the applicant was in possession of the claimed genus. 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).
Thus, one of skill in the art would reasonably conclude that the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the genus of MBM’s as encompassed by the claims.
Claims 19 and 56 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.
Claim 19 is a method which administers an MBM to a subject with a metabolic disorder. Claim 56 is a method wherein the MBM is administered to a subject in an amount effective to treat a metabolic condition and/or improve metabolism. However, the claims are not enabled for treatment of any and all metabolic conditions or for improving “metabolism” as broadly claimed. The MBM of the instant claims is a trispecific molecule that mimicks FGF21 in that it activates FGFR1c/β-Klotho. However, not all metabolic disorders/conditions or metabolism in general are related to FGF21 activity such that administration of the MBM of the instant claims would be effective to treat such conditions. While claim 19 does not specifically recite treatment, the claim administers to a subject with a metabolic disorder and the only disclosed use of such would be for treating. While limitations from the specification are not read into the claims, the claims are read in light of the specification. The art recognizes well over 200 metabolic disorders, many of which are genetic conditions which have no relation or nexus to FGF21 or activation of FGFR1c/β-Klotho. For example, Wilson disease is an inherited disorder caused by a mutation that results in the accumulation of copper in the body; variegate porphyria is an inherited disorder which leads to the build-up of compounds normally involved in the production of heme; Tay-Sachs disease is an inherited neurodegenerative condition caused by a deficit of beta-hexosaminidase A; sarcosinemia characterized by an increased level of the amino acid sarcosine in the blood and urine. The majority of metabolic disorders known to the skilled artisan are not related to FGF21 or activation of FGFR1c/β-Klotho and therefore, would not be treated by the administration of the MBM of the instant claims nor would there be a therapeutically effective amount for such treatment.
Claim 56 is directed treatment by administering to a subject an effective amount to treat the disorder or condition. However, the method fails to indicate what the result is to be achieved in a specific way and merely indicates effective to treat. The instant claim is not enabled for the breadth of treating with an effective amount to treat because the administration of the MBM would not be expected to treat all metabolic disorders or improve all metabolism because the biological effects of the administration of the MBM are limited to those effects that are related to activation of FGFR1c/β-Klotho. Therefore, the claims are not enabled for the reasons provided above.
Claims 58-59 and 61 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.
Claim 58 is directed to a nucleic acid or plurality of nucleic acids encoding the MBM of claim 28. However, there is no requirement that the MBM of claim 28 be a protein as claim 28 only describes the MBM by functional language. Therefore, claim 59 is not enabled for encoding an MBM which is not comprised of amino acids.
Claim 59 is directed to a cell engineered to express the MBM of claim 28. However, “engineered to express” fails to provide any steps or components which would be necessary to express an MBM. Furthermore, if the MBM is not protein or composed of amino acids, it would be impossible for a cell to be engineered to express the MBM.
As pointed out above in the 112(a) rejection of the claims, the instant specification only describes antibody structures which function as the MBM (see claims 7, 14, 34 and 41). A single nucleic acid, without something more, will not encode an MBM which is a bispecific antibody with an scFv or Fab linked to the antibody. Antibodies are comprised of multiple chains and a single nucleic acid which is expressed in a cell would not result in the various chains of the antibody associating properly to form a functional binding molecule. Therefore, the claims are not enabled as currently drafted.
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 22 and 48 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 instant claims recite “reduced effector function”. The term “reduced” in claims 22 and 48 is a relative term which renders the claims indefinite. The term “reduced” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2 and 29 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. The instant claims recite “wherein the MBM is a trispecific binding molecule”. However, claims 2 and 29 depend from claims that recite an MBM which has 3 antigen-binding modules which would be a trispecific binding molecule. Therefore, claims 2 and 29 do not appear to further limit the subject matter of the claims from which they depend. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Allowable Subject Matter
Claims 7, 11-12, 14, 17-18, 34, 38-39 and 41 are 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.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christine J Saoud whose telephone number is (571)272-0891. The examiner can normally be reached M-F, 8am-4pm.
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, Julie Z Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Christine J Saoud/Primary Examiner, Art Unit 1645
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