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 .
Specification
The disclosure is objected to because of the following informalities:
The amendment to the specification on 3/21/2024 inserting the paragraph concerning the sequence listing is no longer accurate. Applicant submitted a new sequence listing on 4/1/2024. This paragraph should have been corrected to reflect the 4/1/2024 sequence listing. In particular, applicant is advised that there is no provision for reciting “approximately” when providing the size of the file in bytes. The actual size must be recited.
Appropriate correction is required.
Claim Objections
Claim 13 is objected to because of the following informalities: The claim has an extraneous comma (“,”) after “host.” 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 9-10 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.
Claim 9 is directed to an antibody that competes for binding to human KLB or monkey KLB with the anti-KLB antibody according to claim 1. The specification does not identify any epitope bound by any antibody encompassed by claim 1. The specification identifies no competing antibodies. There is no disclosed structure/function relationship disclosed for any antibody having the required properties. This genus of antibodies is not adequately described. Note that Test Example 3 is with respect to competitive binding of antibodies hAb991-13, hAb18-98, and hAb-23 and FGF21/FGF19 for binding to KLB. It does not show competition between or among antibodies.
Claim 10 is directed to anti-KLB antibodies according to claim 1 having one or more the recited characteristics. The specification does not provide functional information for the antibodies of claim 1 commensurate with the characteristics recited in claim 1.
Table 7 (mAb-99 humanized antibodies), Table 9 (mAb-18 humanized antibodies), and Table 10 (includes hAb-23 antibody) show binding data.
Paragraph [0149] of the specification states that the experimental results show that the antibodies of the present disclosure have significant activation activity for CHOK1-hKLB&hFGFRIc cells, and the activation degree is stronger than that of the control molecule. This statement is not supported by the specification. Table 13 shows activation of the KLB&FGFR1c receptor by the hAb99-13 antibody but no other antibody.
Paragraph [0152] of the specification states that the experimental results show that the antibodies of the present disclosure have significant activation activity for HEK293T-hKLB&hFGFR1c and the activation activity is stronger than that of the control molecule. This statement is not supported by the specification. Table 14 shows agonistic activity of hAb99-13 and hAb18-8 for the recombinant cell line HEK293T-hKLB&FGFR1c. No activity is disclosed for any other antibody.
Paragraph [0155] of the specification states that the experimental results show that the antibodies of the present disclosure have weak activation activity on HEK293-hFGFR1c, indicating that the activation of human KLB and human FGFR1c stable cell lines by the antibodies of the present disclosure is human KLB-dependent. This statement is not supported by the specification. Table 15 shows this activity for hAb99-13, hAb18-8, and hAb-23. No activity is disclosed for any other antibody.
Antibody hAb-23 has the VH/VL of SEQ ID NOS: 18/19. See specification paragraph [0122].
Antibody hAb99-13 has the VH/VL of SEQ ID NOS: 40/34. See Table 7.
Antibody hAb18-8 has the VH/VL of SEQ ID NOS: 49/57. See Table 9.
These three antibodies are insufficient to adequately describe the subgenus of antibodies having the characteristics of claim 10. The specification fails to adequately describe which characteristics of claim 10, parts (A)-(E) are possessed by each of antibodies of claim 1. There is no disclosed structure/function relationship disclosed for any antibody having any or all of the recited characteristics. Note that antibody hAb99-13 and antibody hAb18-8 do not share the same sets of six CDRs with all of the antibodies in claim 1, parts (i) and (ii), respectively. The subgenus of antibodies encompassed by claim 10 is not adequately described.
Claim 14 is 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 inducing FGF21/FGF19 signaling, does not reasonably provide enablement for all methods embraced by the claim. 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.
Paragraph [0073] of the specification defines “treatment” as including preventing the occurrence or recurrence of a disease, alleviating symptoms, alleviating/reducing any direct or indirect pathological consequences of the disease, preventing metastasis, decreasing the rate of disease progression, ameliorating or alleviating the disease state, and regressing or improving prognosis. In some embodiments, the antibody of the present disclosure is used to delay the development of or slow the progression of a disease. As claim 14 does not require treatment of any particular disease and does not require any particular therapeutic outcome, all aspects of treatment must be enabled.
At least for example, there is no evidence of record nor reason to believe that administration of the claimed antibodies will prevent or cure or reverse symptoms of Alzheimer’s Disease. Note that claim 14 as written is not directed to treating any particular disease.
At least for example there is no evidence of record nor reason to believe that administration of the claimed antibodies will prevent or cure NASH, type 2 diabetes obesity, dyslipidemia, cardiovascular diseases, and/or metabolic syndrome.
At least for example, there is no evidence of record nor reason to believe that administration of the claimed antibodies will reverse diabetic neuropathy or diabetic retinopathy (pathological consequences of type 2 diabetes) or reverse cardiac tissue damage (pathological consequences of cardiovascular disease).
The scope of the claims is not enabled.
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 2, 5, 6, 10, 11, and 14 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.
Regarding claims 2, 5, 6, 10, 11, 14 the phrases “preferably” and “more preferably” render the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 11 is indefinite in reciting a “therapeutically effective amount” in the absence of reciting a therapeutic effect. The claim does not clearly define the amount of antibody required in the composition.
The term “associated” in claim 14 is a relative term which renders the claim indefinite. The term “associated” 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. It is unclear what degree of association with FGF21 and/or FGF19 that is required to provide the metes and bounds for the diseases to be treated..
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.
Claim 4 is 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.
Claim 4 depends upon claim 1. At least for example, claim 2, part (iv) references SEQ ID NOS: 2 and 3; however, the CDRs recited in claim 1 are not present in SEQ ID NOS: 2 and 3. At least for example, the HCDR2 in SEQ ID NO: 2 does not correspond to the HCDR2 in SEQ ID NOS: 40-48. At least for example, claim 4, part (i), references SEQ ID NOS: 30-32 and 33-36 and claim 4, part (ii) references SEQ ID NOS: 50-51 and 52-55. However, the CDRS recited in claim 1 are not present in these SEQ ID NOS. With respect to the “at least 90% sequence identity” limitations in claim 4, this variability must be outside the CDRs required by claim 1; otherwise, the claim would not be properly dependent.
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.
Claims 1, 7-8, and 11 are allowable. The prior art of record does not disclose anti-KLB antibodies having the CDR sequences required by claim 1 or the heavy chain/light chain sequences required by claims 7-8.
With respect to the “at least 90% sequence identity” limitations in claim 7, this variability must be outside the CDRs required by claim 1; otherwise, the claim would not be properly dependent. SEQ ID NO: 78 contains SEQ ID NO: 40 and SEQ ID NO: 79 contains SEQ ID NO: 34 for hAb99-13. SEQ ID NO: 80 contains SEQ ID NO: 49 and SEQ ID NO: 81 contains SEQ ID NO: 57 for hAb18-8. SEQ ID NO: 20 contains SEQ ID NO: 18 and SEQ ID NO: 21 contains SEQ ID NO: 19 for hAb-23.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE P ALLEN whose telephone number is (571)272-0712. The examiner can normally be reached 7:00-3:30 EST Monday-Friday.
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/Marianne P Allen/Primary Examiner, Art Unit 1647
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