DETAILED ACTION
Claims 1-17 are currently pending in the instant application. Claims 1-13, 16, and 17 are rejected. Claims 8-10 are objected. Claims 14 and 15 appear allowable.
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 .
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because page 80 of the specification provides the sequence:
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Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Claim Objections
Claims 8-10 are objected to because of the following informalities: Claim 8 ends in a comma. Claims 9 and 10 do not end in a period. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 2 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 pre-AIA the applicant regards as the invention. Specifically, claim 2 recites the limitation
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in the formula (II):
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There is insufficient antecedent basis for this limitation in the claim as formula II has:
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instead of
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. Notice the nitrogen versus the “W”.
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 12-13 and 16-17 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 a neoplastic disease or autoimmune disease which can be ameliorated by inhibition of bcl-2 in a subject having such a disease does not reasonably provide enablement for the treatment or prevention of any neoplastic or autoimmune 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.
As stated in the MPEP 2164.01 (a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the amount of direction or guidance present,
5. the presence or absence of working examples,
6. the breadth of the claims,
7. the quantity of experimentation needed, and
8. the level of the skill in the art.
In the instant case,
The nature of the invention
The nature of the invention of 12, 13, 16, and 17 are methods of treating any neoplastic or autoimmune disease, such as any cancer or Alzheimer’s disease (see pages 37-38 of the instant specification). Page 32 of the specification provides that the term “treating” includes a subject with a “predisposition toward it”, i.e. prevention. Furthermore, the instant claims cover 'diseases' that are known to exist and those that may be discovered in the future, for which there is no enablement provided.
The state of the prior art and the predictability or lack thereof in the art
The state of the prior art is that the pharmacological art involves screening in vitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. what compounds can treat or prevent which specific diseases by what mechanism). There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face.
The instant claimed invention is highly unpredictable as discussed below:
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute.
Applicants are claiming the treatment of various diseases such as, cancer, Alzheimer’s disease, etc.
Applicants’ claims are also drawn to the treatment or prevention of Alzheimer’s disease. It is the state of the art that there is no known cure or prevention for Alzheimer’s disease and that there are only four medications available in the United States available to temporarily slow the early stages of Alzheimer’s disease. The current drugs for the treatment of Alzheimer’s disease, Aricept, Exelon, Reminyl and Cognex, treat early stages of Alzheimer’s disease by delaying the breakdown of acetylcholine. Memantine, which blocks excess amounts of glutamate treats late stage Alzheimer’s disease. (URL:http://www.cnn.com/2003/HEALTH/conditions/09/24/alzheimers.drug.ap/index.html.
Furthermore, Layzer, Cecil Textbook of Medicine (article enclosed), states that “some degenerative diseases are difficult to classify because they involve multiple anatomic locations” (see page 2050). Alzheimer’s disease has traditionally been very difficult or impossible to prevent or event to treat effectively with chemotherapeutic agents. See e.g., the Cecil Textbook of Medicine, 20th edition (1996), Vol. 2, wherein it is stated that “[t]here is no cure for Alzheimer’s disease, and no drug tried so far can alter the progress of the disease” (pg. 1994).
Applicant’s claims are for the treatment and prevention of various cancers. The state of the prior art is that cancer therapy remains highly unpredictable. The various types of cancers have different causative agents, involve different cellular mechanisms, and consequently, differ in treatment protocol. It is known that the challenge of cancer treatment has been to target specific therapies to pathogenetically distinct tumor types, that cancer classification has been based primarily on morphological appearance of the tumor and that tumors with similar histopathological appearance can follow significantly different clinical courses and show different responses to therapy (Golub et al. page 531) Furthermore, it is known that chemotherapy is most effective against tumors with rapidly dividing cells and that cells of solid tumors divide relatively slowly and chemotherapy is often less effective against them. It is also known in the prior art (Lala et al. page 91) that the role of NO in tumor biology remains incompletely understood with both the promotion and inhibition of NO mentioned for the treatment of tumor progression and only certain human cancers may be treated by selected NO-blocking drugs. These example shows that there are different cellular mechanisms, the unpredictability in the art and the different treatment protocols.
Hence, in the absence of a showing of correlation between all the diseases claimed as capable of treatment by the administration of the compounds of the claims one of skill in the art is unable to fully predict possible results from the administration of the compound of the claims due to the unpredictability, for example, since it is known that the challenge of cancer treatment has been to target specific therapies to pathogenetically distinct tumor types, that cancer classification has been based primarily on morphological appearance of the tumor and that tumors with similar histopathological appearance can follow significantly different clinical courses and show different responses to therapy.
The amount of direction or guidance present and the presence or absence of working examples
The only direction or guidance present in the instant specification is the listing of diseases applicant considers as treatable on pages 37 and 38. Additionally, in vitro data is found on pages 80-83 and In vivo is found on pages 82-83 for the treatment (excluding prevention) of neoplastic and autoimmune diseases which can be ameliorated by inhibition of bcl-2 However, the disclosure does not provide how the in vitro and in vivo data correlates to the treatment and prevention of the assorted diseases claimed when not related to the inhibition of bcl-2.
Further, there is no disclosure regarding how all types of diseases claimed having diverse mechanisms are treated or prevented. Receptor activity is generally unpredictable and a highly structure specific area, and the data provided of is insufficient for one of ordinary skill in the art in order to extrapolate to the other compounds of the claims. It is inconceivable as to how the claimed compounds can treat the extremely difficult diseases embraced by the instant claims.
Applicants have not provided any competent evidence or disclosed tests that are highly predictive for the pharmaceutical use of the instant compounds. Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.” See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The breadth of the claims
The breadth of the claims 12, 13, 16, and 17 are methods of treating any neoplastic or autoimmune disease, such as any cancer or Alzheimer’s disease (see pages 37-38 of the instant specification). Page 32 of the specification provides that the term “treating” includes a subject with a “predisposition toward it”, i.e. prevention. Furthermore, the instant claims cover 'diseases' that are known to exist and those that may be discovered in the future, for which there is no enablement provided.
The quantity of experimentation needed
The quantity of experimentation needed is undue experimentation. One of skill in the art would need to determine what diseases out of the multitude claimed would be benefited by the administration of the compound of the claims.
The level of the skill in the art
The level of skill in the art is high. However, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro and in vivo screening to determine which compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity.
Thus, the specification fails to provide sufficient support of the broad use of the compound of the instant claims for the treatment of the various claimed diseases and disorders as a result necessitating one of skill to perform an exhaustive search for which disorders can be treated or prevented by what compounds of the instant claims in order to practice the claimed invention.
Thus, factors such as “sufficient working examples”, “the level of skill in the art” and “predictability”, etc. have been demonstrated to be sufficiently lacking in the instantly claimed methods. In view of the breadth of the claim, the chemical nature of the invention, and the lack of working examples regarding the activity of the claimed compounds, one having ordinary skill in the art would have to undergo an undue amount of experimentation to use the invention commensurate in scope with the claims.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001 (3/13/1997), states that “ a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[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”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which diseases can be treated or prevented by the compound encompassed in the instant claim, with no assurance of success.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1-11 is/are rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-11 of prior U.S. Patent No. 10,377,755. This is a statutory double patenting rejection.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 12 and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12 and 13 of U.S. Patent No. 10,377,755. Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims anticipate the instantly claimed method claims as the conflicting claims are drawn to
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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.
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/REBECCA L ANDERSON/Primary Examiner, Art Unit 1626 ____________________ 2 September 2026
Rebecca Anderson
Primary Examiner
Art Unit 1626, Group 1620
Technology Center 1600
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