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 .
Applicant’s election without traverse in the reply filed on 6/24/20254 is acknowledged:
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Claims Applicants respectfully submit that at least claims 1-5, 10-11, 13, 15-16, 19, 23-25, 30, 45-47, 57, 61, and 63 cover the elected species and are treated on the merits, below.
Claims 32, 33, 51-53 are withdrawn from consideration as exclusively covering a non-elected invention.
Claim Rejections - Rejection under the Judicially Created Doctrine of
Improper Markush Grouping
Claims 1-5, 10-11, 13, 15-16, 19, 23-25, 30, 45-47, 57, 61 are rejected under the judicially created doctrine of "improper Markush grouping". The Markush group of Formula (VIII) contains a plethora of nested variables. This is an improper grouping of alternatively useable species. MPEP 803.02 describes a Markush grouping as " ... "selected from the group consisting of A, Band C." The examiner respectfully directs the Applicant's attention to MPEP 803.02 shown below for convenience:
"A Markush-type claim recites alternatives in a format such as "selected from the group consisting of A, Band C." See Ex parte Markush, 1925 C.D. 126 (Comm'r Pat. 1925). The members of the Markush group (A, B, and C in the example above) ordinarily must belong to a recognized physical or chemical class or to an art-recognized class. However, when the Markush group occurs in a claim reciting a process or a combination (not a single compound), it is sufficient if the members of the group are disclosed in the specification to possess at least one property in common which is mainly responsible for their function in the claimed relationship, and it is clear from their very nature or from the prior art that all of them possess this property. Inventions in metallurgy, refractories, ceramics, pharmacy, pharmacology and biology are most frequently claimed under the Markush formula but purely mechanical features or process steps may also be claimed by using the Markush style of claiming. (See MPEP § 2173.05(h))."
Furthermore, the members of a proper Markush grouping " ... ordinarily must belong to a recognized physical or chemical class or to an art-recognized class." MPEP 803.02 also states that members of a Markush grouping are " ... sufficiently few in number or so closely related that a search and examination of the entire claim can be made without serious burden." This paragraph of the MPEP is shown below for convenience: "If the members of the Markush group are sufficiently few in number or so closely related that a search and examination of the entire claim can be made without serious burden, the examiner must examine all the members of the Markush group in the claim on the merits, even though they may be directed to independent and distinct inventions. In such a case, the examiner will not follow the procedure described below and will not require provisional election of a single species. (See MPEP § 808.02.)"
A Markush claim contains an "improper Markush grouping" if:
1. The species of the Markush group do not share a "single structural similarity,"
- Meaning they do not belong to the same recognized physical or chemical class
or same art-recognized class (see explanation supra), or
2. The species do not share a common use,
- Meaning they are not disclosed in the specification or known in the art to be
functionally equivalent.
If 1 or 2 above apply to a Markush grouping, a rejection under the judicially approved "improper Markush grouping" doctrine is proper.
The compounds of Formula (I) do not share a "single structural similarity" since there is no common core due to the wide range of compounds possible given variables. For a Markush grouping to be proper, the alternatives represented by the grouping must have a "significant structural element that is shared by all of the alternatives" or the species must all share a common use and recognized as "functionally equivalent". A significant structural element that is shared by all of the alternatives refers to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity. Each alternative does not have a common chemical structure which occupies a large portion of the structure or have a structurally distinctive portion in view of the prior art which is essential to the claimed common activity/properties.
Here, all the groups are highly variable, including the combinations of CDR’s.
Additionally, as a result of the wide range of compounds possible by the instant Markush formula, each compound does not belong to the same recognized physical or chemical class or to the same art-recognized class and no credible evidence for a common use amongst all claimed compounds exists. A person of ordinary skill in the art would understand that compounds with such greatly varied structure cannot be expected to have predictable properties. This is a central concept to basic organic chemistry and common knowledge of those with ordinary skill in the art and taught in the first chapter of the organic text CAREY, FA. Organic Chemistry 6th Ed. McGraw Hill. 2006, chapter 1, p. 9. Therefore, in the absence of evidence to the contrary, all compounds within the metes and bounds of the extraordinarily large Markush grouping of the instant claims cannot be individually envisioned and each expected to be functionally equivalent.
This rejection may be overcome by either amending the claims to include only the species that share a single structural similarity and a common use such as the compounds which have a constant core and are clearly enabled by the instant specification.
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 1-5, 10-11, 13, 15-16, 19, 23-25, 30, 45-47, 57, 61 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 antibody drug conjugates (ADC’s), compositions and methods of using the same.
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 ADC’s, 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 the scope of ADC’s encompassed by the claims. Specifically, Applicant fails to disclose any other ADC’s, 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 ADC’s.
With regard to the functional definition anti-DLK1 antibody, linker or active agent, 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 compounds. At best, it simply indicates that one should test an inordinate number of compounds to see if the compounds can perform the required function. 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 ADC’s.
Claims 3, 4 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 conjugates comprising antibodies with a % homology to HC and LC variable regions.
The specification demonstrates the recited function for the polypeptide encoded by the recited SEQ ID NO’s, but offered no teaching as to what regions of the recited protein were critical for conservation of the recited function and which regions could be modified. So, the specification leaves it to others to discover the nature and scope of substitutions, deletions, and insertions that can be made to arrive at a 90% homology sequence that additionally allows for the required recited activity.
Any use of BLAST homology data to argue that a PHOSITA would be able to address the issue, but 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 was not enough to describe the structure so that a PHOSITA could determine beforehand whether or not a particular structure meets the functional requirements.
Therefore, the PHOSITA cannot determine if the peptides claimed produce a protein that accomplished the recited function from the specification itself in order to meet the written description requirement.
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 1-5, 10-11, 13, 15-16, 19, 23-25, 30, 45-47, 57, 61 and 63 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 1 recites combinations of CDR’s and the dependent claims cover fragments (e.g., HCVF, LCVF) comprising the CDR’s. It is unclear which fragments correspond or comprise the recited CDR’s. Therefore, the intended structures of the antibodies are unclear.
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 1-5, 10-11, 13, 15-16, 19, 23-25, 30, 45-47, 57, 61 and 63 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019050362, as evidenced by counterpart U.S. Publication No. 20210214432 based on an application by Baek et al. (Lim) in view of WO 2017089890, as evidenced by counterpart U.S. Publication No. 20200297865 based on an application by Kim et al. (Kim).
All citations are made with reference to the counterpart U.S. Publications.
Lim teaches the required anti-DLK1 antibodies:
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Lim specifically indicates that the instant antibodies can be formulated into anti-DLK1 antibody drug conjugates:
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Lim may fail to explicitly teach the required X group comprising a linker-active agent moiety. However, at the time of the invention, these linker-active agents were preferred in ADC’s. It is for that proposition that the rejection joins Kim. Specifically, Kim teaches that the elected species was a preferred linker-active agent component in ADC’s for cancer therapy:
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See Example 7B.
In this way, those of ordinary skill could have applied the required linker-active agents in the manner required and in a predictable fashion for the purposes of obtaining providing the instant ADC’s. As outlined above, Lim teaches that the required anti-DLK1 antibodies were intended for ADC’s. Kim is added for the proposition the recited linker-active agents are applicable to these ADC’s. Specifically, Kim teaches that the particular known technique of using the recited linker-active agents in ADC’s was 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 ADC’s, such as those suggested by Lim, would have yielded predictable results. Accordingly, using the recited linker-active agents for the purposes of preparing the instant anti-DLK1 ADC’s 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 1-5, 10-11, 13, 15-16, 19, 23-25, 30, 45-47, 57, 61 and 63 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-11 of U.S. Patent No. 11306141 in view of WO 2017089890, as evidenced by counterpart U.S. Publication No. 20200297865 based on an application by Kim et al. (Kim).
Although the claims at issue are not identical, they are not patentably distinct from each other.
The conflicting claims cover ADC’s with the required anti-DLK1 antibodies. Kim is added for the proposition the recited linker-active agents are applicable to these ADC’s. Specifically, Kim teaches that the particular known technique of using the recited linker-active agents in ADC’s was 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 ADC’s, such as those suggested by Lim, would have yielded predictable results. Accordingly, using the recited linker-active agents for the purposes of preparing the instant anti-DLK1 ADC’s would have been prima facie obvious.
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