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 .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 7/20/2026 has been entered.
Claims 1, 3, 6, 7, 20-21, 33, 49, 62-69, 71-77, 104 and 105 are now pending. Claims 1, 21, 104 and 105 are amended.
Claims 1, 3, 6, 7, 20-21, 33, 49, 62-69, 71-77, 104 and 105 are currently under prosecution.
Maintained Rejection
(Arguments Addressed)
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, 3, 6, 7, 20-21, 33, 49, 62-69, 71-77, 104 and 105 remain 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. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to a method of treating a tumor or cancer in a subject in need thereof, comprising administering to the subject an effective amount of a CD93/IGFBP7 blocking agent. The claims recite that the CD93/IGFBP7 blocking agent: (1) specifically inhibits the IGFBP7 signaling pathway, (2) blocks the interaction between CD93 and IGFBP7, (3) is an anti-CD93 antibody, (4) blocks the interaction between CD93 and MMRN2, (5) does not block the interaction between CD93 and MMRN2, or (6) an anti-IGFBP7 antibody. Thus, the claims identify the CD93/IGFBP7 blocking agent by function only, where the function is listed above in (1)-(6).
The instant specification discloses the following:
Agent Inhibiting the IGFBP7/CD93 Signaling Pathway
[0118]
The agent may be any of an antibody, a polypeptide, a peptide, a polynucleotide, a peptidomimetic, a natural product, a carbohydrate, an aptamer an avimer, an anticalin, a speigelmer, or a small molecule. Particular examples of what the agent may be are described below, and methods for identifying suitable agents feature in a subsequent aspect of the application. In some embodiments, the agent is a fusion protein (such as a fusion protein that comprises a half-life extending domain (e.g., a Fc domain)).
Anti-CD93 or Anti-IGFBP Antibodies
[0125]
A. Anti-CD93 Antibodies
[0143]
In some embodiments, the anti-CD93 antibody is anti-human CD93 monoclonal antibody selected from the group consisting of EPR5386 (abcam), 3D12 (sigma-aldrich), 1A4 (sigma-aldrich), 1A10E10, 2F7D11, R139, R3, mNI-11, X-2, and MM01.
[0147]
B. Anti-IGFBP7 Antibodies
[0162]
In some embodiments, the anti-IGFBP7 antibody is anti-human IGFBP7 monoclonal antibody selected from the group consisting of mAb AEDO-9 (clone name, same for the following antibodies) (Bosterbio). ID9E7 (LifeSpan BioSciences), 5A4A9) (LifeSpan BioSciences), 192520 (R&D systems), H3 (Santa Cruz/Biotechnology), 40012B (R&D Systems), EPR11912(B) (Abcam), MM0346-3N37 (Abcam), 01 (i.e., MM01, Sino Biological), 003 (i.e., R003, Sino Biological). In some embodiments, the anti-human IGFBP7 monoclonal antibody is mAb 003 (i.e., R003, Sino Biological) or a humanized version thereof.
Thus, the instant specification discloses: 9 anti-CD93 antibodies and 10 anti-IGFBP7 antibodies, as shown above in [0143] and [0162], that function to treat cancer. The specification fails to disclose any structural sequences or structures required of the CD93/IGFBP7 blocking agent to possess the function to (1) inhibit the IGFBP7 signaling pathway, (2) blocks the interaction between CD93 and IGFBP7, (3) is an anti-CD93 antibody, (4) blocks the interaction between CD93 and MMRN2, (5) does not block the interaction between CD93 and MMRN2, or (6) an anti-IGFBP7 antibody.
To provide adequate written description and evidence of possession of the claimed CD93/IGFBP7 blocking agent genus, the instant specification can structurally describe representative agents that function as listed above in (1)-(6), or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
Although Applicants may argue that it is possible to screen for IGFBP7 or CD93 agents that function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n 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.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future agents yet to be discovered that may function as claimed. The CD93 or IGFBP7 antigens provides no information about the structure of the agent that binds to it.
In this case, the only factor present in the claims is a recitation of the agent function: (1) inhibit the IGFBP7 signaling pathway, (2) blocks the interaction between CD93 and IGFBP7, (3) is an anti-CD93 antibody, (4) blocks the interaction between CD93 and MMRN2, (5) does not block the interaction between CD93 and MMRN2, or (6) an anti-IGFBP7 antibody.
The claims broadly encompass any agent that functions inhibit the IGFBP7/CD93 signaling pathway and treat cancer. The instant specification fails to describe structural features common to the members of the genus, which features constitute a substantial portion of the genus because the instant specification discloses 9 anti-CD93 antibodies and 10 anti-IGFBP7 antibodies that functions as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antigen binding protein does, rather than what it is. Other than the antibodies listed in paragraphs above, the specification fails to provide any structural features coupled to the claimed functional characteristics.
Given the lack of representative examples to support the full scope of the claimed CD93/IGFBP7 blocking agent and those used in the claimed methods, and lack of reasonable structure-function correlation with regards to the unknown sequences in the antibodies that provide CD93 or IGFBP7 binding function and cancer treating function, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of the CD93/IGFBP7 blocking agents that is required to practice the claimed invention. Since the specification fails to adequately describe the product to which the claimed method uses, it also fails to adequately describe the method.
Examiner Suggestion: Amend the claims to recite the structure critical to the anti-CD93/IGFB7 blocking agent; such as an anti-CD93 antibody comprising all six heavy and light chain CDRs, or comprising both the heavy and light chain variable domain; or an anti-IGFBP7 antibody comprising all six heavy and light chains CDRs or comprising both heavy and light chain variable domains.
Response to Arguments
Applicant describe the invention and argue that one skilled in the art at the time of the present application would have reasonably expected that anti-CD93 or anti-IGFBP7 blocking antibodies of different formats can achieve desired anti-tumor effects. Furthermore, the inventors of the present application have demonstrated consistent anti- tumor effects of exemplary anti-CD93 blocking antibody or exemplary anti-IGFBP7 antibody in various animal models implanted with cancer cells of different kinds, including pancreatic cancer, melanoma, and multiple breast cancer kinds including TNBC (e.g., Examples 2, 6-7, 11-13, and 15; FIGS. 2A, 6B-6C, 18C, 20C, 23A-23B). Applicant argues that the subject matter presently claimed is directed to novel methods of treating a cancer or tumor in a subject by administering into the subject an anti-CD93 or an anti-IGFBP7 blocking antibody. Applicants respectfully submit that when the invention is directed to novel methods (e.g., methods of treatment) of using a class of agent, disclosure of certain species of the class of the agent is sufficient to support for such claims when at least some of the agents are known and/or disclosed in the application. See e.g., In re Herschler. Applicant argues that the CD93/IGFBP7 blocking agent recited in present claims which is a) an anti-CD93 antibody that specifically binds to CD93 or b) an anti-IGFBP7 antibody that specifically binds to IGFBP7 were not only known but also accessible to the public at the time of the present application as evidenced by the present application as filed. Applicant lists two examples in Figure 16: a) anti-CD93 antibodies that block the interaction between CD93 and IGFBP7 were known at the time, such as MM01 from SinoBiological, and b) anti- IGFBP7 antibodies that block the interaction between CD93 and IGFBP7 were known at the time, such as R003 from SinoBiological.
Applicant argues that methods for generating, screening, and obtaining anti-CD93 and anti-IGFBP7 antibodies were known and because the specification expressly discloses representative antibodies together with screening assays, the amount of structural description required is correspondingly reduced under Capon.
Applicant also presents the Federal Circuit's recent decision in Teva V. Eli Lilly (Teva Pharmaceuticals International GmbH V. Eli Lilly & Co., No. 24-1094 (Fed. Cir. Apr. 16, 2026), provided here as Exhibit A) provides further confirmation that Rochester is inapposite here. Applicants argue that assuming arguendo that CD93 antibodies were less extensively studied than physiologically active steroids in Herschler, neither Herschler nor any subsequent Federal Circuit decision establishes that a claimed class of agents must satisfy any quantitative threshold of prior-art development before it may serve as the well-known tools of a method claim. Applicants argue the fact that anti-CD93 antibodies and anti-IGFBP7 antibodies bind different proteins does not establish a lack of written description. Applicants argue like the antibodies in Teva that bound different regions of CGRP, Applicants' disclosed antibodies interact with different components of the same signaling interaction yet perform the same claimed therapeutic function by disrupting the CD93/IGFBP7 signaling pathway.
Applicant’s arguments have been considered but are not persuasive.
Examiner points again to MPEP 2163 II.A.3(a):
3. Determine Whether There is Sufficient Written Description to Inform a Skilled Artisan That Inventor was in Possession of the Claimed Invention as a Whole at the Time the Application Was Filed
An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that "[w]ithout such disclosure, the claimed methods cannot be said to have been described.").
In this situation, the claims are drawn to a method of treating a tumor or cancer, comprising administering an effective amount of CD93/IGFB97 blocking agent that inhibits the IGFBP7/CD93 signaling pathway and blocks the interaction between CD93 and IGFPB7. No compounds are disclosed that can be used in the claimed methods, and no disclosure of which agents, including antibodies, that can function as claimed. Thus, to provide support for the claimed method, there needs to be support for the products used therein.
With regards to Teva, the case notes the following:
“Although there was just one humanized anti-CGRP antagonist antibody, it is also disclosed several murine version and prior art CGFR antagonist antibodies” [pg 13, 2nd paragraph]
“As already discussed, a reasonable jury could have found that, by priority date, (1) anti-CGFRP antagonist antibodies and methods of making them were already known, and (2) humanization was a routine procedure. The specification disclosed several examples of murine anti-CGRP antagonist antibodies and prior-art methods of humanization.” [pg 14-15]
The Teva case is directed to humanized versions of well-known murine antibodies. Anti-CGRP antibodies are well known in the art and the method of humanizing antibodies is also well known. The specification of the Teva case well-described anti-CGRP proteins, which is not the case this instant case This is unrelated case the claimed antibodies are not well known in the art, nor were they well described in the instant specification. Applicant also is claiming two different proteins, which is not the same as anti-CGRP antibody that can bind to different sites on the same protein. With regards to In re Herschler, this case is drawn to physiologically active steroids, which are well known and well established in the art. “CD93 antibodies” and “IGFBP7 antibodies” are not well known in the art and the instant specification only discloses a set number of manufacturer antibodies and commercial monoclonal antibodies. Thus, there is a limited number of these monoclonal antibodies and do not provide full scope of the genus of the claimed antibodies, which is the opposite case of what happened in Teva.
With regards to screening for agents that function as claimed: Examiner points again to the following: the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n 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.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future agents yet to be discovered that may function as claimed. The CD93 or IGFBP7 antigens provides no information about the structure of the agent that binds to it.
Applicant argues that this does not apply to the present case as the present case is “based on clear support and compelling evidence”.
However, the present case does indeed lack support as anti-CD93 and anti-IGFBP7 are not well known antibodies and were not extensively described in the instant specification. A handful of commercial antibodies does not provide support or provide guidance in the art to give possession of these antibodies.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH A ALSOMAIRY whose telephone number is (571)272-0027. The examiner can normally be reached Monday-Friday 7:30 AM to 5:30 PM.
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, Gregory Emch can be reached at (571) 272-8149. 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.
/SARAH A ALSOMAIRY/Examiner, Art Unit 1646
/Zachariah Lucas/Supervisory Patent Examiner, Art Unit 1600
Prosecution Insights