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 .
No Requirement for Restriction/Election was mailed in this application.
Claims 1-22 are pending and examined upon their merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is the national stage entry of PCT/CN2021/135203 filed on 3 December 2021, which claims the benefit of Chinese Applications: CN202111366667.X filed 18 November 2021, and CN202011405490.5 filed 3 December 2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claims 1-22 have an earliest effective US filing date of 3 December 2020.
Specification
Applicant is put on notice that the disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Specifically page 32 of the Disclosure contains an executable code (“By comparing the IMGT (http://imgt.cines.fr)”). 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:// or other browser-executable code. See MPEP § 608.01. Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities: The claim contains an abbreviation (“CTGF”) that is not spelled out upon its first appearance in the claims (i.e. “Connective Tissue Growth Factor”). 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 18 and 22 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 treating a CTGF-associated disease selected from a fibrotic disease, hypertension, diabetes, myocardial infarction, arthritis, a CTGF-associated disease of cellular proliferation, atherosclerosis, glaucoma, or cancer; does not reasonably provide enablement for preventing any CTGF-associated disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure would require undue experimentation include:
A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
The breadth of the claims.
The broadest reasonable interpretation of the claimed method is that it provides for the prevention of any CTGF-associated disease (claim 18). The scope of diseases encompassed is vast – including any growth/proliferation of tissue throughout the human body.
The state of the prior art.
CTFG was known as a central mediator of tissue growth and fibrosis (see Lipson et al., Fibrogenesis & Tissue Repair, 5(Suppl 1):S24, 2012). While there was a well-established nexus between CTGF and each of the claimed diseases associated with proliferation (fibrotic disease, hypertension, diabetes, myocardial infarction, arthritis, cellular proliferation, atherosclerosis, glaucoma, or cancer), there was nothing in the art, prior to the filing date of the application, that suggested anti-CTFG antibodies could prevent any of these diseases. Therefore, there was no evidence in support of administering anti-CTGF antibodies could result in preventing any of the claimed diseases with a reasonable expectation of success. For example, the following prior art teaches profibrotic pathways in chronic kidney disease (a.k.a. renal fibrosis) are complex requiring not only CTGF, but also EGF and PDGF (Kok et al., Nature Reviews Nephrology, 10: 700-711, 2014; Abstract only). Thus, there was much unpredictability with respect to preventing disease at the time of filing.
Level of skill in the art.
Regarding preventing diseases, a person having ordinary skill would be a medical doctor in charge of prescribing administered treatments. Thus, the level of skill in the art, with respect to the claimed invention, is high.
The amount of direction provided by the inventor; and the existence of working examples.
Additionally, there is no guidance within the instant disclosure that overcomes the unpredictability within the literature. Example I of the disclosure is directed to inhibition of bleomycin-induced pulmonary fibrosis comprising administering CTGF antibodies after bleomycin. This is not predictive of prevention before disease induction, but rather enables treatment of after the disease has begun. Example II is directed to administering CTGF antibodies after initiation of xenograft tumors, which is not predictive of preventing cancer before the presence of tumors. The only remaining working examples within the disclosure (Examples 2.1 through 2.5) are directed to formulation of the antibody compositions themselves. Therefore, the specification as filed does not provide guidance that overcomes the unpredictability within the art of preventing disease.
The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. In the decision of Genentech, Inc, v. Novo Nordisk, 42 USPQ 2d 1001, (CAFC 1997), the court held that:
"[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" and that "[t]ossing out the mere germ of an idea does not constitute enabling disclosure". The court further stated that "when there is no disclosure of any specific starting material or of any of the conditions under which a process is to be carried out, undue experimentation is required; there is a failure to meet the enablement requirements that cannot be rectified by asserting that all the disclosure related to the process is within the skill of the art", "[i]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement".
The instant specification is not enabling because one cannot follow the guidance presented therein, or within the art at the time of filing, and practice the claimed method of preventing disease without first making a substantial inventive contribution.
The nature of the invention; and the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Given that the nature of the invention is directed to in vivo prevention of a wide array of diseases associated with tissue growth/proliferation, a person having ordinary skill in the art would have to perform multiple in vivo experiments – in either human clinical trials or animal models that are predictive of preventing the full array of CTGF-associated diseases encompassed by the claims - in order to demonstrate use of the method with a reasonable expectation of success. The amount of experimentation required for enabling the invention commensurate in scope with what is claimed, goes beyond what is considered “routine” or “reasonable” within the art (see MPEP 2164.06), and constitutes undue further experimentation in order to use the method of the invention to successfully prevent any CTGF-associated disease.
Therefore, Claims 18 and 22 are rejected under 35 U.S.C. 112, first paragraph, for failing to meet the enablement requirement. This rejection may be obviated by removing the “preventing” limitation from these claims.
Allowable Subject Matter
Claims 1-17 and 19-21 are directed to allowable products and depending claims specifically comprising those products. The anti-CTGF antibody sequences of instant claims 1, 2 and 19-21 are novel and non-obvious in the art. Therefore, the pharmaceutical compositions, lyophilized formulations, reconstituted solutions, and articles of manufacture comprising the anti-CTGF antibodies are also novel; as is the method of preparing a lyophilized formulation comprising these antibodies.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STACEY NEE MACFARLANE whose telephone number is (571)270-3057. The examiner can normally be reached M-F 7:30-5 (EST) & Sat. A.M..
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/STACEY N MACFARLANE/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675