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 .
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.
Claims 3, 5 and 8 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 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.
The rejected claims cover percent identities of the heavy/light chains and an FR region, which is a framework region which is a subdivision of the variable region (Fab) of the claimed antibody.
Here, PHOSITA could envision sequences that meet the percent identity requirement. Further, by using conservative substitutions, a PHOSITA could likely envision an antibody having the same tertiary structure as the claimed antibody.
However, there is no teaching in the specification that the conservation of structure (whether in the DNA or encoded polypeptide) would be a surrogate for conservation of the function claimed, i.e., an antibody with anti-SIRPα activity. That is, there is no teaching as to which residues of the in the recited HC, LC or FR regions that could be altered while still conserving the function of the antibody.
The specification demonstrated the recited function for the antibodies encoded by SEQ ID NO’s, but offered no teaching as to what regions of the recited regions are critical for conservation of the recited function and which regions can be modified. The specification leaves it to others to discover the nature and scope of substitutions, deletions, and insertions that can be made to the regions to arrive at the recited percent identity that additionally allows for anti-SIRPα activity.
Even if applicants attempted to use BLAST homology data to argue that a PHOSITA would be able to address the issue, the evidence is accorded little weight and characterized as an invitation to experiment.
Even though the DNA/polypeptides that could be envisioned by the PHOSTIA could be easily tested as set forth in the specification for conservation of the recited function, this is not enough to describe the structure so that a PHOSITA could determine beforehand whether or not a particular structure meets the functional requirements.
Here, the anti-SIRPα antibody variant is claimed by percent identity and function. However, a PHOSITA cannot determine if a given variant produces an antibody that accomplished the recited function from the specification itself in order to meet the written description requirement.
Claims 14, 18 and 19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating cancer, does not reasonably provide enablement for treating other diseases. 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 standard for determining whether the specification meets the enablement requirement [in accordance with the statute] 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). See also United States v. Telectronics, Inc., 857 F.2d 778, 785, 8 USPQ2d 1217, 1223 (Fed. Cir. 1988) ("The test of enablement is whether one reasonably skilled in the art could make or use the invention from the disclosures in the patent coupled with information known in the art without undue experimentation."). A patent need not teach, and preferably omits, what is well known in the art. In re Buchner, 929 F.2d 660, 661, 18 USPQ2d 1331, 1332 (Fed. Cir. 1991); Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1384, 231 USPQ 81, 94 (Fed. Cir. 1986), cert. denied, 480 U.S. 947 (1987); and Lindemann Maschinenfabrik GMBH v. American Hoist & Derrick Co., 730 F.2d 1452, 1463, 221 USPQ 481, 489 (Fed. Cir. 1984). Determining enablement is a question of law based on underlying factual findings. In re Vaeck, 947 F.2d 488, 495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991); Atlas Powder Co. v. E.I. du Pont de Nemours & Co., 750 F.2d 1569, 1576, 224 USPQ 409, 413 (Fed. Cir. 1984).” See M.P.E.P. § 2164.
Here, the disclosed nature of the invention is treating cancer with anti-SIRPα antibodies. In this regard, determining a particular antibody’s activity in the body is not routine and the level of ordinary skill in the art of treating disease is high, as an ordinary artisan in this art needs specialized knowledge of the complex etiology and pharmacology of diseases. Applicant is reminded of the heightened enablement for these types of inventions: Specifically, the amount of guidance or direction needed 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. 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. [I]n the field of chemistry generally, there may be times when the well-known unpredictability of chemical reactions will alone be enough to create a reasonable doubt as to the accuracy of a particular broad statement put forward as enabling support for a claim. This will especially be the case where the statement is, on its face, contrary to generally accepted scientific principles. Most often, additional factors, such as the teachings in pertinent references, will be available to substantiate any doubts that the asserted scope of objective enablement is in fact commensurate with the scope of protection sought and to support any demands based thereon for proof. [Footnote omitted.].
Therefore, either the state of the art or the specification needs to establish that the instant anti-SIRPα antibodies can treat the scope of diseases claimed.
The prior art teaches that cancer cells highly expressed CD47 that activate SIRP α and inhibit macrophage-mediated destruction. In one study, engineered high-affinity variants of SIRPα antagonized CD47 on cancer cells and caused increase phagocytosis of cancer cells. Another study (in mice) found anti-SIRPα antibodies helped macrophages to reduce cancer growth and metastasis, alone and in synergy with other cancer treatments. See:
Weiskopf et al., Science. 2013 May 30;341(6141);
Potential new cancer treatment activates cancer-engulfing cells, 2017, downloaded 4 March 2016 from https://www.sciencedaily.com/releases/2017/02/170206084054.htm and
Yanagita et al., JCI Insight. 2017 Jan 12;2(1):e89140.
Therefore, the use of anti-SIRPα antibodies for treatment of cancer may be characterized as “known”, but use of such compounds to treat other diseases is not predictable since there is no nexus between the use of these antibodies and treatment of other diseases besides cancer. Also, it is unpredictable whether an antibody used for cancer treatment can also be used to treat other diseases, since there doesn’t appear to be a link between cancer treatment with antibodies and treatment of other diseases with the same antibody.
The specification fails to remedy the state of the art. Here the specification shows activity of anti-SIRPα antibodies against cancer cells. Therefore, a nexus may be established between in vitro results and treatment of cancer. The specification does not provide any additional examples or guidance on how to use the recited anti-SIRPα antibodies to treat other diseases. Thus, the specification provides sufficient teachings only for the enablement of treatment of cancers. The prior art provides no compensatory guidance and it would require undue experimentation to practice the invention for treating diseases other than cancer. The amount of experimentation would be undue because it would require determining how to use the antibodies to treat these diseases. Specifically, as outlined above, it is not routine to determine how an antibody will act on complex biochemistry to treat different conditions. In the instant case, it is only known that the instant anti-SIRPα antibodies have cytotoxic activity against SIRPα-positive cancer cells. This means that significant experimentation would be required to determine how the antibodies can be used to treat other diseases not related to SIRPα. Those of ordinary skill in the art cannot extrapolate between the anti-SIRPα activity of the antibodies and the etiology of other diseases. Moreover, there is little guidance, in both the prior art and the specification, with respect to the use of such antibodies to to treat diseases other than 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.
Claims 14, 18 and 19 are 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 14 generically recites cancer but also recites solid tumor separately. The claim also recites specific examples of cancer but are also solid tumors. Therefore, it is unclear what conditions Applicant intends to cover by “cancer” and “solid tumor”.
Claim 14 recites “nervous system disease”. It is unclear what diseases are specifically included by this term.
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 1-3, 5-9, 11, 12, 14-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8-21 of copending Application No. 18/870,605. Although the claims at issue are not identical, they are not patentably distinct from each other.
Specifically, the conflicting claims recite antibodies with an anti-SIRPα binding domain that anticipates the antibodies covered by the rejected claims:
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The conflicting claims also recite associated nucleic acids, expression systems and methods covered by the rejected claims.
Alternatively, the difference between the antibodies covered by the conflicting claims and those covered by the rejected claims is that the conflicting claims may not recite the instant antibodies and associated nucleic acids and expression systems with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the structural elements of the instant anti-SIRPα antibodies with sufficient guidance, particularity, and with a reasonable expectation of success, that the instant invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
The recited FR regions are included in the heavy and light chains of recited in the conflicting claims. Moreover, antibody-drug conjugates targeting tumor antigens, such as anti-SIRPα, are well within the purview of those of ordinary skill, and therefore, prima facie obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
A search of electronic peptide database files uncovered WO 2023231705 and counterpart US 2025/0326840 (published from 18/870,605, which is cited in the double patenting rejection, above) filed by QURE BIOTECHNOLOGY (SHANGHAI) CO., LTD. However, these references do not qualify as prior art under any sub-paragraph of section 102 against the instant application.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's acting supervisor, Gregory Emch, can be reached at telephone number 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646