DETAILED ACTION
Claims 1, 4-7, and 10-24 are currently pending in the instant application. Claims 1, 4, 5, 7, 10-14, 17-20, 23, and 24 are allowed. Claims 6, 15, 16, 21, and 22 are rejected. The closest prior art of record is Liu et al. (WO 2021018003) which fails to teach or suggest applicant’s instantly claimed invention.
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 Preliminary Amendment filed 8 February 2024 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows: “the disclosures of which are hereby incorporated by reference in its entirety.”
MPEP 211.02 and MPEP 201.06(c)(IV) state the following in regard to “Incorporation by Reference” and PCT Rule 20.6, Rule 20.7 and Rule 4.18 are directed specifically to International applications:
MPEP 211.02, in-part
For applications filed on or after September 21, 2004, a claim under 35 U.S.C. 119(e) or 120 and 37 CFR 1.78 for benefit of a prior-filed provisional application, nonprovisional application, international application designating the United States, or international design application designating the United States that was present on the filing date of the continuation or divisional application, or the nonprovisional application claiming benefit of a prior-filed provisional application, is considered an incorporation by reference of the prior-filed application as to inadvertently omitted material, subject to the conditions and requirements of 37 CFR 1.57(b). The purpose of 37 CFR 1.57(b) is to provide a safeguard for applicants when all or a portion of the specification and/or drawing(s) is (are) inadvertently omitted from an application. See MPEP § 201.06 and 217. However, applicants are encouraged to provide in the specification an explicit incorporation by reference statement to the prior-filed application(s) for which benefit is claimed under 35 U.S.C. 119(e) or 120 if applicants do not wish the incorporation by reference to be limited to inadvertently omitted material pursuant to 37 CFR 1.57(b). See 37 CFR 1.57(c). See also MPEP §§ 217 and MPEP § 608.01(p).
When a benefit claim is submitted after the filing of an application, and the later-filed application as filed did not incorporate the prior-filed application by reference, applicant cannot add an incorporation by reference statement of the prior application. An incorporation by reference statement added after an application’s filing date is not effective because no new matter can be added to an application after its filing date (see 35 U.S.C. 132(a)). See Dart Indus. v. Banner, 636 F.2d 684, 207 USPQ 273 (C.A.D.C. 1980). See also 37 CFR 1.57(b).
MPEP 201.06(c)(IV), in-part
201.06(c) 37 CFR 1.53(b) and 37 CFR 1.63(d) Divisional-Continuation Procedure [R-07.2015]
IV. INCORPORATION BY REFERENCE
An applicant may incorporate by reference the prior application by including, in the continuing application-as-filed, an explicit statement that such specifically enumerated prior application or applications are “hereby incorporated by reference.” The statement must appear in the specification. See 37 CFR 1.57(c) and MPEP § 608.01(p). The inclusion of this incorporation by reference statement will permit an applicant to amend the continuing application to include subject matter from the prior application(s), without the need for a petition provided the continuing application is entitled to a filing date notwithstanding the incorporation by reference. For applications filed prior to September 21, 2004, the incorporation by reference statement may appear in the transmittal letter or in the specification. Note that for applications filed prior to September 21, 2004, if applicants used a former version of the transmittal letter form provided by the USPTO, the incorporation by reference statement could only be relied upon to add inadvertently omitted material to the continuation or divisional application.
An incorporation by reference statement added after an application’s filing date is not effective because no new matter can be added to an application after its filing date (see 35 U.S.C. 132(a)). If an incorporation by reference statement is included in an amendment to the specification to add a benefit claim under 35 U.S.C. 120 after the filing date of the application, the amendment would not be proper. When a benefit claim under 35 U.S.C. 120 is submitted after the filing of an application, the reference to the prior application cannot include an incorporation by reference statement of the prior application. See Dart Indus. v. Banner, 636 F.2d 684, 207 USPQ 273 (C.A.D.C. 1980).
20.6 Confirmation of Incorporation by Reference of Elements and Parts
(a) The applicant may submit to the receiving Office, within the applicable time limit under Rule 20.7 , a written notice confirming that an element or part is incorporated by reference in the international application under Rule 4.18 , accompanied by:
(i) a sheet or sheets embodying the entire element as contained in the earlier application or embodying the part concerned;
(ii) where the applicant has not already complied with Rule 17.1(a) , (b) or (b-bis) in relation to the priority document, a copy of the earlier application as filed;
(iii) where the earlier application is not in the language in which the international application is filed, a translation of the earlier application into that language or, where a translation of the international application is required under Rule 12.3(a) or 12.4(a) , a translation of the earlier application into both the language in which the international application is filed and the language of that translation; and
(iv) in the case of a part of the description, claims or drawings, an indication as to where that part is contained in the earlier application and, where applicable, in any translation referred to in item (iii).
(b) Where the receiving Office finds that the requirements of Rule 4.18 and paragraph (a) have been complied with and that the element or part referred to in paragraph (a) is completely contained in the earlier application concerned, that element or part shall be considered to have been contained in the purported international application on the date on which one or more elements referred to in Article 11(1)(iii) were first received by the receiving Office.
(c) Where the receiving Office finds that a requirement under Rule 4.18 or paragraph (a) has not been complied with or that the element or part referred to in paragraph (a) is not completely contained in the earlier application concerned, the receiving Office shall proceed as provided for in Rule 20.3(b)(i) , 20.5(b) , 20.5(c) , 20.5bis(b) or 20.5bis(c) , as the case may be.
20.7 Time Limit
(a) The applicable time limit referred to in Rules 20.3(a) and (b) , 20.4 , 20.5(a) , (b) and (c) , 20.5bis(a) , (b) and (c) , and 20.6(a) shall be:
(i) where an invitation under Rule 20.3(a) , 20.5(a) or 20.5bis(a) , as applicable, was sent to the applicant, two months from the date of the invitation;
(ii) where no such invitation was sent to the applicant, two months from the date on which one or more elements referred to in Article 11(1)(iii) were first received by the receiving Office.
(b) Where neither a correction under Article 11(2) nor a notice under Rule 20.6(a) confirming the incorporation by reference of an element referred to in Article 11(1)(iii)(d) or (e) is received by the receiving Office prior to the expiration of the applicable time limit under paragraph (a), any such correction or notice received by that Office after the expiration of that time limit but before it sends a notification to the applicant under Rule 20.4(i) shall be considered to have been received within that time limit.
4.18 Statement of Incorporation by Reference
Where the international application, on the date on which one or more elements referred to in Article 11(1)(iii) were first received by the receiving Office, claims the priority of an earlier application, the request may contain a statement that, where an element of the international application referred to in Article 11(1)(iii)(d) or (e) , or a part of the description, claims or drawings referred to in Rule 20.5(a) , or an element or part of the description, claims or drawings referred to in Rule 20.5bis(a) is not otherwise contained in the international application but is completely contained in the earlier application, that element or part is, subject to confirmation under Rule 20.6 , incorporated by reference in the international application for the purposes of Rule 20.6 . Such a statement, if not contained in the request on that date, may be added to the request if, and only if, it was otherwise contained in, or submitted with, the international application on that date.
The instant application is a 371 application which has an International filing date of 23 August 2022. The incorporation by reference statement is being added by way of a Preliminary Amendment filed 8 February 2024, which is after the instant application's International filing date of 23 August 2022. Therefore, the “incorporation by reference” statement being added to the instant specification by way of the Preliminary Amendment is deemed new matter.
Applicant is required to cancel the new matter in the reply to this Office Action.
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 6, 16, 21, 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 the treatment of EGFR and/or ALK mediated cancers, fails to provide the required enablement for prevention or treatment of all cancers. 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 instant claims are drawn to a method of preventing or treating cancer. The specification fails to provide information that would allow the one skilled in the art to practice preventing cancer or treating all cancers.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is
permissible, if it is merely routine, or if the specification in question provides a reasonable
amount of guidance with respect to the direction in which the experimentation should
proceed to enable the determination of how to practice a desired embodiment of the
claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
the nature of the invention
the state of the prior art
the predictability of the art
the amount of direction or guidance provided
the presence or absence of working examples
the breadth of the claims
the quantity of experimentation necessary
the relative skill of those in the art
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention - is a method of preventing or treating cancer comprising administering a compound or composition of crystal form 1.
The state of the prior art - the pharmacological art requires the screening of potential drug candidates in vitro and in vivo to determine if the drug candidates exhibit the desired pharmacological activities.
In order to treat a disease: one would need to precisely identify what the disease is, identify what biological target is connected with the disease, demonstrate that the drug candidate in some way modulates the normal processes of the biological target, and demonstrate that a patient benefited from such modification without detrimental side effects. Typically, this process includes in vitro laboratory screening, preclinical in vivo screening, and three phases of clinical trials. Once this arduous process has been successfully completed by a drug candidate, subsequent drug candidates will benefit from the established proof of concept. The subsequent drug candidates must demonstrate a substantial correlation between their biological activity and that of the known drug candidate.
In order to prevent a disease: one would need to precisely identify those subjects likely to acquire such a disease, administer Applicant’s claimed invention, and demonstrate that the patient did not develop the disease as a result of the administration of the claim invention.
In the instant case, the prior arts recognize that therapeutic agents have potential to exhibit antagonistic property toward the EGFR and ALK kinases, which can be used to treat EGFR or ALK -mediated cancers (Zubair et al. Int. J. Mol. Sci. 2023; 24: 2651 and Sullivan et al. Ther Adv Med Oncol. 2016;8(1):32–47). There is no prior art that recognizes and EGFR or ALK inhibitor can treat all cancers or prevent any cancer.
The predictability or unpredictability of the art – the law recognizes the pharmaceutical art as an unpredictable art and requires each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18 24 (CCPA 1970). Accordingly, the more unpredictable an area is the more specific disclosure is necessary in order to satisfy the statute. Section 2164.02 of the MPEP provides:
"[C]orrelation” as used herein refers to the relationship between in vitro and in
vivo animal model assays and a disclosed or a claimed method of use . . . if the
art is such that a particular model is recognized as correlating to a specific
condition, then it should be accepted as correlating unless the examiner has
evidence that the model does not correlate.
In light of these remarks, the Examiner finds that one of ordinary skill in the art would agree with the court; that is, the pharmaceutical art is unpredictable. Thus, a substantial correlation is necessary for establishing the potential of new therapeutics.
Additionally, within pharmaceutics, the art of cancer therapeutics is well known to be unpredictable due to the differing etiologies and mechanisms of action for particular cancers. There are more than 200 known cancers; treatment applicable to one is unlikely to be applicable to another. Bianchi et al. (Current Opinion in Cell Biology. 2020; 63:135-143) attributes this unpredictability to tissue specificity, noting most cancer driver genes are mutated in a tissue-dependent manner, which affects therapeutic response (page 135). For example, BRAF inhibition is an effective therapy for BRAF-mutated melanomas, but not BRAF-mutated colon cancer (page 140); same mutation, different tumors, therefore different therapeutic outcomes. Therefore, from the well-established state of cancer arts, a skilled practitioner would not conclude all cancers could be treated, managed or improved with the same therapeutic agent.
The amount of direction or guidance presented – the instant specification provides an explanation of the biological activity of EGFR and ALK on pages 1-2, and discusses the implication of EGFR and/or ALK inhibitors in the treatment of EGFR and/or ALK-mediated cancers. There is no direction or guidance provided that supports a use of a EGFR and/or ALK inhibitor as a drug for preventing cancer or treating all cancers. EGFR and ALK assay data is found on page 32-36. Pages 37-39 provide in vivo data for certain ALK tumors.
The amount of guidance or direction to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. MPEP § 2164.03 (quoting In re Fisher, 427 F.2d 833, 839, 166 USPQ 18 24 (CCPA 1970)). As identified supra, the pharmaceutical art is recognized as unpredictable.
Thus, in order to support a claim for preventing or treating all cancers a vast amount of evidence is required because such a claim is not supported by the prior art or the instant specification.
The presence or absence of working examples - there are no working or prophetic examples in the specification that demonstrate that the instant compounds or compositions thereof may prophylactically treat and prevent cancer, nor any examples that the instant compounds would treat a cancer not mediated by EGFR and/or ALK. The assays in the specification demonstrate that the instant compounds were tested for their ability to inhibit the kinases in vitro (pages 32-36 of the instant specification).
The breadth of the claims – is incommensurate in scope with the disclosure because a fair reading of the specification fails to support a finding that the compounds of crystal form I may prevent or treat all cancers in a patient.
The quantity of experimentation necessary – generally speaking, the amount of experimentation to transform a molecule into medicine is vast and the success thereof is low. Recent statistics indicate that the attrition rates during drug development remain high. Schafer et al. Drug Discovery Today 2008, 13 (21/22), 913-916. The article makes clear that there are many steps necessary to promote a new molecular entity toward its clinical use, any one of which is cumbersome.
For instance, Schafer et al. discloses: "proof of concept trials have failed when the decision to enter clinical development was based on preclinical experiments using the wrong compound, the wrong experimental model, or the wrong endpoint.” It can be gleaned from this article that a plethora of experimentation is needed to identify the lead compound (i.e. one among many in a Markush-type claim), to establish which preclinical tests are predictive of clinical success, and to establish which diseases are the best to target for each lead compound.
There is generally a vast amount of experimentation to take a drug from bench to the clinic. See e.g., Horig et al. Journal of Translational Medicine 2004, 2(44) (“Successful drug development requires satisfying a matrix of domains from relevance to the disease and the drug-ability of the target through feasibility and convenience of drug delivery, demonstration of favorable benefit-risk profile in order to achieve a drug label that reflects physician and patent acceptance.") The Examiner finds that one of ordinary skill in the art would agree with the statements in these articles; that is, the amount of experimentation required to enable a pharmaceutical drug is extensive.
The level of skill in the art - the level of ordinary skill in the art may be found by inquiring into: (1) the type of problems encountered in the art; (2) prior art solutions to those problems; (3) the rapidity with which innovations are made; (4) the sophistication of the technology; and (5) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of those factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983).
Based on the typical education level of the active workers in the field of pharmaceuticals and/or medicine, as well as the high degree of sophistication required to solve problems encountered in the art, the Examiner finds that a person of ordinary skill in the art would have at least a college degree in a field related to medicine and/or the pharmaceutical art and at least four years of work experience, i.e. a masters or doctorate level scientist/clinician.
Therefore, claims 6, 16, 21, and 22 are rejected because the Examiner finds that the Wands factors suggest a conclusion that the skilled artisan would not be able to make and use the instant invention without undue experimentation, although the level of skill for an ordinary person in the art is high. That is, due to the breadth of the claims, the unpredictability of the art, the lack of guidance or direction from the disclosure, the lack of any working examples, and the amount of experimentation needed illustrate that a person having ordinary skill in the art would not be able to prevent or treat all cancer.
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.
Claim 15 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 15 contains multiple trademark/trade names such as Olaparib, Rubraca, Zejula, Keytruda, Opdivo, Tecentriq, Imfinzi, and Bavencio . 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 additional anticancer drugs or antitumor drugs and, accordingly, the identification/description is indefinite.
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 15 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. Specifically, claim 15 is dependent upon claim 5 which has “other anticancer drug or antitumor drug”, however, claim 15 references “the cytotoxic drug”, “the hormone drug”, “The antimetabolite drug”, “the tumor-targeted drug”, the PARP inhibitor drug”, “the adjuvant therapy drug”, and “the antitumor biological drug”, which are not found in claim 5 but are found in claim 14. 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.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA L ANDERSON whose telephone number is (571)272-0696. The examiner can normally be reached Monday-Friday from 6am-2pm.
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, Andrew Kosar can be reached at 571-272-0913. 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.
/REBECCA L ANDERSON/Primary Examiner, Art Unit 1626 ____________________ 20 July 2026
Rebecca Anderson
Primary Examiner
Art Unit 1626, Group 1620
Technology Center 1600
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