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.
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 1-25 and 28-44 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 anti-DLL-3 antibody-drug conjugates.
To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”); In re Gosteli, 872 F.2d 1008, 1012 (Fed. Cir. 1989) (“the description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed”).
With regard to the recited genus of conjugates, the following applies:
Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 94 USPQ2d 1161 (Fed. Cir. 2010) states that “...a generic claim may define the boundaries of a vast genus of chemical compounds...the question may still remain whether the specification, including the original claim language, demonstrates that the applicant invented species sufficient to support a claim to a genus”. See page 1171.
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.
See also Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a “laundry list” disclosure of every possible moiety does not constitute a written description of every species in a genus because it would not “reasonably lead” those skilled in the art to any particular species.
Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) states that “it is well established in our law that conception of a chemical compound requires that the inventor be able to define it so as to distinguish it from other materials, and to describe how to obtain it”.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or structural features common to the members of the genus, which features constitute a substantial portion of the genus, so that one of skill in the art can “visualize or recognize” the members of the genus (Emphasis added). Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997).
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. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)(“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B(i), the court states, "An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention."
Courts have stated that “[i]n claims involving [non-genetic] chemical materials, generic formulae usually indicate with specificity what the generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate description of the claimed genus.” Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089 (1998). (emphasis added).
There is no such specificity here, nor could one skilled in the art identify conjugates encompassed by the claims. Specifically, Applicant desires patent protection for anti-DLL-3 antibody-drug conjugates. However, in view of the above, the specification does not provide adequate written description of the claimed genus of conjugates. Specifically, Applicant fails to disclose any other conjugates, besides those covered by the formulas in the specification and claims, and in relation to the above, these disclosed species or subgenre do not represent the substantial variety covered by the genus of conjugates.
With regard to the functional definition of the drug or linker components, the specification does not clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed (see Vas-Cath at page 1116) because the specification contains almost no information by which a person of ordinary skill in the art would understand that the inventors possessed the all of the recited conjugates. At best, it simply indicates that one should test an inordinate number of compounds to see if the compounds can perform the required function of a linker or drug, see In re ’318 Patent Infringement Litigation, 583 F.3d 1317, 1327 (Fed. Cir. 2009) (“[A]t the end of the day, the specification, even read in light of the knowledge of those skilled in the art, does no more than state a hypothesis and propose testing to determine the accuracy of that hypothesis. That is not sufficient.”).
The Examiner acknowledges that a working example or exemplified embodiment is not necessarily a requirement for description. However, where a generic claim term is present in a claim, as in the present application, and defined only by functional characteristics, the specification must convey enough information, e.g., via sufficient representative examples, to indicate invention of species sufficient to constitute the genus. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 967 2 (Fed. Cir. 2002). The written description requirement “requires a description of an invention, not an indication of a result that one might achieve if one made that invention.” Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997); see also Novozymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d 1336, 1350 (Fed. Cir. 2013) (“A patent...‘is not a reward for the search, but compensation for its successful conclusion.’ ... For that reason, the written description requirement prohibits a patentee from ‘leaving it to the ... industry to complete an unfinished invention.’” (citations omitted)).
Accordingly, the specification lacks adequate written description for the recited anti-DLL-3 antibody-drug conjugates.
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.
Claims 37 and 38 are 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. The intended uses recited in claims 37 and 38 do not further limit the composition of claim 36, from which these claims depend.
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.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-21, 28-44 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2021/007371 and counterparts US Publication No. 20220348648 and US Patent No. 12,441,789 (collectively “WO 371”) in view of:
WO 2014/130879 (WO 879); and
Saunders et al., SCIENCE TRANSLATIONAL MEDICINE, vol. 7, no. 302, 26 August 2015, pages 1-15 (Saunders); and
WO 2019/234220 (WO 220); and
US 20170218078 (US 078); and
WO 2019/131988 (WO 988).
WO 371 (see paragraphs [088], [0089], [0092], [0109] - [0111], [0115], [0180]; claims 1-10) discloses anti-DLL3 antibodies comprising CDRs or heavy chain variable domains and light chain variable domains being identical to those defined in present claims. The four exemplified monoclonal antibodies of the present application form also the examples of WO 371 (see in particular example 8). The general teaching of WO 371 encompasses antibody-drug conjugates wherein the antibody is one of the disclosed anti-DLL3 antibodies of WO 371 that shall enable the delivery of therapeutic agents to DLL3-positive cancer cells for anti-cancer treatments (see paragraphs [0234], [0235], [0263], [0265], [0267], [0276], [0277]; claims 17-19). The general teaching of WO 371 also comprises the use of linkers for attaching a drug to the disclosed anti-DLL3 antibodies of WO 371 (see paragraphs [0122], [0123], [0125] - [0127], [0129]). The teachings of WO 371 relating to antibody-drug conjugates and linkers represent general aspects which may be combined with the anti-DLL3 antibodies specifically disclosed in the examples of WO 371.
The difference between the antibodies and conjugates covered in the rejected claims and those disclosed by WO 371 is that WO 371 and the claimed inventions does not teach the invention 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, based on the above, WO 371 teaches the structural elements of the claimed antibodies and conjugates with sufficient guidance, particularity, and with a reasonable expectation of success, that the 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 rejected claims recited drug-to-antibody ratios (DAR) and conjugation strategies. However, the recited conjugation strategies that are within the purview of those of ordinary skill. Moreover, DAR is results-effective variable which is optimized. Therefore, using these conjugations strategies or DAR, in the absence of an unexpected benefit, would have been prima facie obvious.
WO 879 (see examples) and Saunders disclose the anti-DLL3 antibody SC16LD6.5 used as reference in the present application, and drug-linker conjugates thereof wherein the drug is a pyrrolobenzodiazepine dimer. These conjugates are proposed for the treatment of DLL3-expressing tumors, in particular pulmonary tumors
The in vivo pharmacological effects reported on figures 1-3, 12, 13 cannot indeed be considered to apply to the claims encompassing anti-DLL3 antibodies incompletely defined with only some of the CDRs or with only light chain variable domains or heavy chain variable domains, and antibodies bearing mutations and variations so as to have at least 95% sequence identity with the VH and VL domains of the antibodies 2-C8-A, 10-018-A, 6-G23-F without however any guarantee of exhibiting the claimed specificity for DLL3.
The antibody 7-l1B is shown to be a non-specific antibody (see figure 11 and paragraph [0070] of the present application), thereby not fulfilling the claimed specificity for DLL3 and lacking a crucial aspect for in vivo pharmaceutical uses. Therefore, no particular technical effect that could be useful for in vivo pharmaceutical uses is considered to be associated with rejected claims covering the antibody 7-I1-B.
In this manner, the instant anti-DLL3 antibodies, and drug-linker conjugates thereof wherein the drug is a pyrrolobenzodiazepine dimer were well within the purview of those of ordinary skill. Accordingly, using the recited antibodies in combination with the recited drug-linkers for the purposes of providing the instant conjugates would have been prima facie obvious.
WO 220 also discloses anti-DLL3 antibodies:
comprising claimed SEQ ID NO: 8, 9, 10 (see sequences 25, 26, 27);
comprising claimed SEQ ID NO: 13, 14, 15 (see sequence 224);
comprising sequence 210 having 86.5% identity with claimed SEQ ID NO: 23, 24, 25;
comprising sequence 224 having 93.25% identity with claimed SEQ ID NO: 12 and 89.5% identity with claimed SEQ ID NO: 32;
comprising sequence 74 having 95.8%, 96.2%, 96.7% identity with respectively
claimed SEQ ID NO: 63, 64, 65;
comprising sequence 243 having 96.2%, 96.6%, 97.7% with respectively claimed SEQ ID NO: 67, 68, 69;
comprising claimed SEQ ID NO: 18, 19, 29 (see respectively sequences 7, 8, 152).
US 078 discloses an anti-DLL3 antibody comprising sequence 194 having 93% identity with claimed SEQ ID NO:22.
WO 988 (see sequence 95) discloses an anti-DLL3 antibody having 99.1% identity with claimed SEQ ID NO:27.
In the absence of any unexpected benefit, those of ordinary skill would have a reasonable expectation of using these antibodies since they have anti-DLL3 activity.
Claims 22-27 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2021/007371 (WO 371) in view of US 20160297890 (US 890).
US 980 teaches the following drug-linkers:
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192
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216
410
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In this way, those of ordinary skill could have applied these drug-linkers in the manner required and in a predictable fashion for the purposes of obtaining the recited conjugates. As outlined above, the WO 371 teaches the recited anti-DLL3 antibodies and conjugates thereof. US 890 is added for the proposition the recited drug-linkers are applicable to these conjugates. Specifically, US 890 teaches that the particular known technique of using the recited drug-linkers in antibody-drug conjugates was recognized as part of the ordinary capabilities of one skilled in the art. In this manner, those of ordinary skill would have recognized that applying the known technique to antibody-drug conjugates, such as those that use anti-DLL3 antibodies as taught by WO 371, would have yielded predictable results. Accordingly, using the recited drug-linkers for the purposes of providing anti-DLL3 antibody drug conjugates would have been prima facie obvious.
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 1-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12441789 in view of:
WO 2014/130879 (WO 879); and
Saunders et al., SCIENCE TRANSLATIONAL MEDICINE, vol. 7, no. 302, 26 August 2015, pages 1-15 (Saunders); and
WO 2019/234220 (WO 220); and
US 20170218078 (US 078); and
WO 2019/131988 (WO 988).
Although the claims at issue are not identical, they are not patentably distinct from each other. Specifically, the antibodies covered in the conflicitng claims anticipate those of covered in the rejected claims. Alternatively, the difference between the antibodies covered in the conflicting claims and those covered by the recjected claims is that the conflicitng claims may fail to recite the instant antibodies 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 antibodies with sufficient guidance, particularity, and with a reasonable expectation of success, that the 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 ancillary references demonstrate that the instant antibodies and conjugates covered in the rejected claims are prima facie obvious, as outlined above.
Claims 1-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-75 of U.S. Application No. 18/272,049 in view of:
WO 2014/130879 (WO 879); and
Saunders et al., SCIENCE TRANSLATIONAL MEDICINE, vol. 7, no. 302, 26 August 2015, pages 1-15 (Saunders); and
WO 2019/234220 (WO 220); and
US 20170218078 (US 078); and
WO 2019/131988 (WO 988).
Although the claims at issue are not identical, they are not patentably distinct from each other. Specifically, the antibodies covered in the conflicting claims anticipate those of covered in the rejected claims. Alternatively, the difference between the antibodies covered in the conflicting claims and those covered by the rejected claims is that the conflicting claims may fail to recite the instant antibodies 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 antibodies with sufficient guidance, particularity, and with a reasonable expectation of success, that the 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 ancillary references demonstrate that the instant antibodies and conjugates covered in the rejected claims are prima facie obvious, as outlined above.
This is a provisional double patenting rejection.
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, Janet Epps-Smith, can be reached at telephone number (571)272-0757. 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