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 .
Status of Claims
Claims -----1-14 are currently pending and under examination.
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. The claims have an earliest effective filing date of 06/23/2021, corresponding to application Japan 2021-103819
Information Disclosure Statement
The Information Disclosure Statements filed on 04/02/2024, 04/26/2024, 06/06/2024, 09/12/2024, 11/20/2024, 03/13/2025, 06/26/2025, 07/18/2025, 08/13/2025, 08/29/2025, 09/19/2025, 10/06/2025, 12/10/2025, 01/12/2026, 02/23/2026, 03/19/2026, and 04/24/2026 have been considered.
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 1-14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. The claimed methods encompasses preventing cancer and medicaments for use in preventing cancer. Although the specification is enabled for treating cancer, the specification is not enabled for preventing cancer. 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.
MPEP § 2164.01 states:
The standard for determining whether the specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261, 270 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? That standard is still the one to be applied. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Accordingly, even though the statute does not use the term “undue experimentation,” it has been interpreted to require that the claimed invention be enabled so that any person skilled in the art can make and use the invention without undue experimentation. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
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.” These factors include but are not limited to:
The breadth of the claims;
The nature of the invention;
The state of the prior art;
The level of one of ordinary skill;
The level of predictability in the art;
The amount of direction provided by the inventor;
The existence of working examples; and
The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The factors most relevant to this rejection are 1) the amount of direction provided by the inventor and 2) the existence of working examples. In the instant case, the amount of direction provided by the inventor and existence of working examples disclosed in the specification, as filed, would not be sufficient to enable the skilled artisan to make and/or use the claimed invention at the time the application was filed without undue experimentation.
(1) The amount of direction provided by the inventor - The amount of guidance or direction needed to enable an invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004). Due to the high level of unpredictability in the area of disease prevention, particularly cancer prevention, the skilled artisan would need significant guidance in preventing cancer by practicing the claimed method. The skilled artisan recognizes that keeping individuals free of cancer indefinitely is an intractable proposition, if not now wholly impossible, given, for example, that cancers are widely heterogeneous diseases, having widely varying pathologies and etiologies, and with causes that are multifactorial and as yet only partially characterized and poorly understood. It is generally recognized that a disease cannot be prevented unless and until its causes are fully appreciated and understood to a degree that it becomes possible to intercede effectively to block its onset or development by any cause.
(2) The existence of working examples – The examples of the specification demonstrate methods that may be used to treat (cure or ameliorate) cancer; however there is no showing in the specification of any means by which one skilled in the art could prevent cancer. Therefore one skilled in the art would be subject to undue experimentation to practice the instant invention as it is currently claimed.
In conclusion upon careful consideration of the Wands factors that are used to determine whether undue experimentation is required to practice an invention, the amount of direction provided by the inventor and the working examples provided, as filed, is not deemed sufficient to enable the skilled artisan to make and/or use the invention commensurate in scope with the instant claims at the time the application was filed without undue experimentation.
Claim 14 is 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Claim 14 recites a method of treating cancer, comprising administering to a subject an anti-CAPRIN-1 antibody. One skilled in the art would readily appreciate that an anti-CAPRIN-1 antibody could be used to inhibit a CAPRIN-1-expressing cancer; however the claim is drawn to a method of inhibiting any cancer by administering an anti-CAPRIN-1 antibody. Absent empirical determination one skilled in the art would be unable to envision which tumors that do not express anti-CAPRIN-1 would be inhibited by administering the claimed anti-CAPRIN-1 antibody. Applicant is informed that this written description issue may be overcome by amending the claim to specifically recite a method of inhibiting a anti-CAPRIN-1-expressing cancer.
Claims 1-6 and 9-14 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Claim 1 is drawn to a medicament for treatment and/or prevention of cancer, comprising an antibody or a fragment thereof having an immunological reactivity with CAPRIN-1 protein, and a topoisomerase I inhibitor.
The claims encompass a large number of anti-CAPRIN-1 antibodies having diverse heavy and light chain CDR amino acid sequences. Following a review of the specification, it appears that Applicant has disclosed numerous anti-CAPRIN-1 binding domains, specifically, those recited in claims 7 and 8; however in view of this disclosure, Applicant is claiming a broad genus of molecules that would be expected to encompass multiple anti- CAPRIN-1 binding domains having diverse heavy and light chain CDR sequences. Even though Applicant has disclosed numerous species within said genus, the specification does not provide adequate written description for the entire claimed genus, because one skilled in the art would be unable to immediately envision, recognize, or distinguish at least most of the members comprised within the genus claimed, specifically, which light and heavy chain CDR sequences (and combinations of said CDR sequences) give rise to antibody molecules capable of binding CAPRIN-1. As detailed below Applicant’s disclosure is not sufficient to demonstrate possession of the entire claimed genus, and as such Applicant’s disclosure does not satisfy the written description requirement of 35 U.S.C. 112(a).
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
PNG
media_image1.png
18
19
media_image1.png
Greyscale
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. In the instant case, Applicant has disclosed numerous species within the genus claimed; however given the substantial antibody structure variation within the genus, the disclosure of said species comprised within the claimed genus is not sufficiently representative of the entire genus.
Furthermore Applicant has not disclosed relevant, identifying characteristics of CDR region amino acid sequences (or combinations thereof) that confer upon an antibody the ability to bind CAPRIN-1, because the instant specification does not provide structural antibody features that correlate with a functional ability to bind CAPRIN-1. To elaborate on why the claimed antibodies lack adequate written description, Mariuzza (Annu. Rev. Biophys. Biophys. Chem., 16: 139-159, 1987) reviews the structural basis of antigen-antibody recognition and teach that naturally occurring conventional antibodies comprise two polypeptides, the so-called light and heavy chains. The antigen-combining site of an antibody is a three-dimensional structure that fully comprises six CDRs, three each from the light and heavy chains. The amino acid sequences of the CDRs are hypervariable, as the amino acid residues contained within the CDRs determine much of the antibody’s antigen-binding specificity. In view of Mariuzza, it is apparent that antibodies having less than all six CDRs that form the antigen binding site of a conventional antibody in their proper context of heavy and light chain variable domains do not describe the particularly identifying structural feature of the antibody that correlates with the antibody’s ability to bind antigen. Absent a description of the at least minimal structural features correlating with a functional ability to bind CAPRIN-1 which are shared by members of a genus commonly sharing this function, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish which heavy and light chain CDR amino acid sequences (or combinations thereof) may be combined such that the resultant heavy and light chain variable regions comprise six CDRs that confer the ability to bind CAPRIN-1.
Furthermore while the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains. For example in a series of experiments involving a monoclonal antibody to Legionella pneumophilia serotype 1, McCarthy et al. (J. Immunol. Methods, 251(1-2): 137-149, 2001) demonstrated that a single VH CDR3 substitution of tyrosine to serine at position 95 resulted in the total loss of antigen recognition in an ELISA. Lin et al. (African Journal of Biotechnology, 10(79):18294-18302, 2011) teach that a single amino acid substitution in the VL CDR3 of an anti-avian infectious bronchitis virus (IBV) single-chain antibody (ZL.80) may abrogate binding. For example at Figure 3, Lin et al. demonstrate that replacing either the Cys105 or Asp106 residue in the VL CDR3 of ZL.80 with an alanine residue reduces binding to near negative control levels. Lin et al. also teach that some single amino acid substitutions in the VL CDR3 of ZL.80 may significantly improve binding. For example replacing the Val108 residue in the VL CDR3 of ZL.80 with a tyrosine residue results in a 12.9-fold increase in affinity compared to parental ZL.80. Accordingly absent empirical determination, one skilled in the art would be unable to predict or envision which CDR residues should be combined such that a resultant antigen-binding site is capable of binding CAPRIN-1. The general knowledge and level of skill in the art does not adequately supplement the omitted description, because specific, not general, guidance is needed. Since the disclosure fails to describe relevant, identifying structural characteristics, in the form of heavy and light chain CDR amino acid sequences, that correlate with the ability to bind CAPRIN-1, and because the disclosed species detailed above are not sufficient to describe the claimed genus, it is submitted that the written description requirement of 35 U.S.C. 112(a) has not been met.
Although screening techniques can be used to isolate antibodies that possess the ability to bind CAPRIN-1, Applicant is reminded that the written description requirement of 35 U.S.C. 112 is severable from the enablement provision. As stated in Vas-Cath Inc. v. Mahurkar (CA FC) 19 USPQ2d 1111, 935 F2d 1555, “The purpose of the ‘written description’ requirement is broader than to merely explain how to ‘make and use’; the applicant must also convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.”
Accordingly given the unpredictability associated with antibody CDR region changes on antigen binding and given the lack of particularity with which the claimed antibodies are described in the specification, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish at least most of the members of the genus to which the claims are directed, and therefore the specification would not reasonably convey to the skilled artisan that Applicant was in possession of the claimed invention at the time the application was filed.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-14 are rejected under 35 U.S.C. 102a1 as being anticipated by Okano et al (US20120301476; published 11/29/2012).
Okano et al teach a medicament and method for treatment of cancer comprising an antibody against CAPRIN-1 (Okano et al, pg. 12, paragraph 0124) as an active ingredient with immunoreactivity (Okano et al, pg. 117, claim 1) and irinotecan (Okano et al, pg. 9, paragraph 0095) wherein the CAPRIN-1 antibody comprises heavy chain variable region reference SEQ ID NO: 43 (comprises 100% sequence identity to instant SEQ ID NO: 39, which comprises the instant SEQ ID NOs: 36-38) and light chain variable region SEQ ID NO: 47 (comprising 100% sequence identity to instant SEQ ID NO: 43, which comprises the instant SEQ ID NOs: 40-42). The antibodies were reactive to CAPRIN-1 protein having an amino acid sequence shown by any one of even numbered SEQ ID NOs: 2-30 (100% sequence identity to even number instant SEQ ID NOs: 2-30) (Okano et al, pg. 20, paragraph 0180). Therefore the invention of Okano et al meets the limitations of claims 1-3, 7-8 and 12-14.
Regarding claim 4, 10, and, 11 Okano et al teach the antibody is reactive to the cell surface of breast cancer cells (Okano et al, pg. 18, paragraph 0167).
Regarding claim 5, Okano et al teach the antibody can bind a CAPRIN-1 polypeptide comprising SEQ ID NO: 37 (100% sequence identity to instant SEQ ID NO: 31, pg. 101)
Regarding claim 6, Okano et al teach that the antibody can be a monoclonal antibody (Okano et al, pg. 18, paragraph 0167).
Regarding claim 9, Okano et al teach that the antibody can be humanized or chimeric (Okano et al, pg. 7, paragraph 0079).
Nonstatutory Double Patenting
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 1-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over 1) claims 1-14 of copending Application No. 19/105,447 (reference application), 2) claims 1-18 of copending Application No. 19/137,714 (reference application), 3) claims 1-20 of copending Application No. 19/105,407 (reference application), 4) claims 1-20 of copending Application No. 19/105,394 (reference application), 5) claims 1-20 of copending Application No. 19/103,661 (reference application), 6) claims 1-20 of copending Application No. 19/103,152 (reference application), 7) claims 1-19 of copending Application No. 18/573,750 (reference application), 8) claims 1-14 of copending Application No. 18/292,656 (reference application), 9) claims 1-18 of copending Application No. 18/292,094 (reference application), 10) claims 1-14 of copending Application No. 18/292,078 (reference application), 11) claims 1-32 of copending Application No. 17/910,549 (reference application), 12) claims 4, 6, 8-12, 14, and 17-22 of copending Application No. 17/910,544 (reference application), and 13) claims 1, 7-13, and 16-20 of copending Application No. 17/910,538 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other, because the instant and conflicting claims both recite the same antibodies, as well as the use of said antibodies in the treatment of cancer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPHINE K DARPOLOR whose telephone number is (571)272-0115. The examiner can normally be reached 7:30ET-4:30ET.
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, Samira Jean-Louis can be reached at (571)270-3503. 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.
/J.K.D./Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
Prosecution Insights