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 .
The rejection under section 112(a), scope of enablement is withdrawn since he claims have been limited to methods of treating cancer.
The rejection under section 112(b) is withdrawn in view of the amendments in connection with this ground of rejection.
The rejections under sections 112(a), lack of written description” is maintained:
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 1-6, 25, 35, 38, 41, 42, 44, 46, 49, 52, 57-59 remain 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 methods of administering and antibody drug conjugate comprising an anti-191P4D12 antibody comprising the CDRs of the heavy chain variable region set forth in SEQ ID NO:22 and CDRs of the light chain variable region set forth in SEQ ID NO:23.
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 CDR’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 CDR’s encompassed by the claims. Specifically, Applicant fails to disclose any other CDR’s, besides those covered by 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 CDR combinations.
With regard to the functional definition of the CDR’s that bind anti-191P4D12, 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 sequence combinations to see if the compounds can perform the required binding, 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)).
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.”).
Accordingly, the specification lacks adequate written description for the recited antibody drug conjugates comprising an anti-191P4D12 antibody comprising the CDRs of the heavy chain variable region set forth in SEQ ID NO:22 and CDRs of the light chain variable region set forth in SEQ ID NO:23.
Applicant argues that those of ordinary skill can ascertain the required CDR’s:
PNG
media_image1.png
196
640
media_image1.png
Greyscale
PNG
media_image2.png
245
664
media_image2.png
Greyscale
However, section 112(a) has three separate requirements, see MPEP 2161 (“The written description requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1341, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc) (If Congress had intended enablement to be the sole description requirement of § 112, first paragraph, the statute would have been written differently.) Vas-Cath, Inc.v.Mahurkar, 935 F.2d 1555, 1562, 19 USPQ2d 1111, 1115 (Fed. Cir. 1991) (While acknowledging that some of its cases concerning the written description requirement and the enablement requirement are confusing, the Federal Circuit reaffirmed that under 35 U.S.C. 112, first paragraph, the written description requirement is separate and distinct from the enablement requirement and gave an example thereof.); In re Barker, 559 F.2d 588, 194 USPQ 470 (CCPA 1977), cert. denied, 434 U.S. 1064 (1978). See also, e.g., Vasudevan Software, Inc. v. MicroStrategy, Inc., 782 F.3d 671, 681-685, 114 USPQ2d 1349, 1356, 1357 (Fed. Cir. 2015) [emphasis applied]”).
In the instant case, the required CDR’s may be fully enabled, since their determination may be done without undue experimentation. However, as outlined above, 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 instant CDR’s.
Here, the specification offers no generic teaching as to what regions of the recited antibody were critical for conservation of the recited anti-191PD12 function and which regions could be modified or what amino acid sequences within the variable domains of antibodies directly interact with antigens.
Here, the specification leaves it to others to discover those sequences that can be considered CDR’s that additionally allows for recited anti-191P4D12 activity.
Applicant argues that the specification provides detailed guidance as to how determine the CDR sequences using the Kabat, AbM, Chothia, Contact, IMGT, and AHon numbering systems, all of which were well-known to those skilled in the art at the time the application was filed. However, this evidence is accorded little weight and characterized as an “invitation to experiment”, 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 PTAB also noted that 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 CDR functional requirements.
Rather, the PHOSITA must be able to determine if a sequence accomplishes the recited CDR function from the specification itself in order to meet the written description requirement.
However, the specification here leaves it to others to discover which sequences can be CDR’s that additionally allows for anti-191P4D12 activity since the specification offered no teaching as to what regions of the VH and VL chains can be CDR’s
Even though sequences could be envisioned by the PHOSTIA and could be easily tested as set forth in the specification for conservation of the recited anti-191P4D12 function, this is not enough to describe a CDR so that a PHOSITA could determine beforehand whether or not a particular structure meets the anti-191P4D12 functional requirements.
The rejections under section 102 are withdrawn in favor of the following new ground of rejections under this section, which were necessitated by Applicant’s amendments.
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, 25, 35, 38, 41, 42, 44, 49, 52, 57-59 are rejected under 35 U.S.C. 103 as being unpatentable over obvious over US 20150306245 A1 (hereinafter “Agensys”) in view of Rajc et al., Pathology - Research and Practice. 2017, Vol. 213, No. 9, pages 1102-1108 (hereinafter “Rajc”) in further view of Diamantis et al., British Journal of Cancer (2016) 114, 362–367 (hereinafter “Diamantis”).
Agensys discloses a method of preventing or treating cancer in a subject (a method of preventing or treating cancer in. a subject; abstract; paragraphs [0030), [0046)), comprising administering to the subject an effective amount of an antibody drug conjugate (comprising administering to the subject an effective amount of an antibody drug conjugate; abstract; paragraphs [0046), [0424)), wherein the antibody drug conjugate comprises an antibody or antigen binding fragment thereof that binds to 191P4D12 conjugated to one or more units of monomethyl auristatin E (MMAE) (wherein the antibody drug conjugate comprises an antibody or antigen binding fragment thereof that binds to 191P4Dl2 conjugated to one or more units of monomethyl auristatin E; abstract; paragraph [0459)).
The antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions (CDRs) (wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising complementarity determining regions; paragraph [0150)) comprising the amino acid sequences of the CDRs of the heavy chain variable region set forth in SEQ ID NO: 22 (residues 20-136 of SEQ ID NO: 7 of the Agensys reference are 100% identical to Applicants' SEQ ID NO: 22, identified as Anti-191P4D12 mAb Ha22-2(2,4)6.1 variable heavy chain; figure 3A; claim 1) and a light chain variable region comprising CDRs (a light chain variable region comprising CDRs; paragraphs [0151]) comprising the amino acid sequences of the CDRs of the light chain variable region set forth in SEQ ID NO: 23 (residues 23-130 of SEQ ID NO: 8 of the Agensys reference are 100% identical to Applicants' SEQ ID NO: 23, identified as Anti-191P4D12 mAb Ha22-2(2,4)6.1 variable light chain; figure 3B; claim 1); and wherein the subject has breast cancer (paragraph [0047), [0175)).
Agensys does not disclose wherein the subject has hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer. However, Rajc discloses wherein the subject has hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer (wherein the subject has hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer; page 1103, second column, fourth paragraph) and 191P4D12 expression (Nectin-4 (191P4D12) expression in luminal B HER2 negative breast cancer; abstract).
It would have been obvious to one of ordinary skill in the art at the time of the invention to have modified the disclosure of Agensys, to include wherein the subject has hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer, as disclosed by Rajc, in order to better provide effective targeted therapy for a patient having said cancer.
Agensys and Rajc, in combination, disclose the method of claim 1. Agensys does not disclose wherein the HR+/HER2- breast cancer is estrogen receptor (ER) positive and/or progesterone receptor (PR) positive, and HER2 negative. Rajc discloses wherein the HR+/HER2- breast cancer is estrogen receptor (ER) positive and/or progesterone receptor (PR) positive (the HR+/HER2- breast cancer is estrogen receptor (ER) positive and/or progesterone receptor (PR) positive; page 1103, second column, fourth paragraph), and HER2 negative (page 1103, second column, fourth paragraph). It would have been obvious to one of ordinary skill in the art at the time of the invention to have modified the disclosure of Agensys, to include the HR+/HER2- breast cancer is estrogen receptor (ER) positive and/or progesterone receptor (PR) positive, as disclosed by Rajc, in order to better provide effective targeted therapy for a patient having said cancer.
Agensys and Rajc, in combination, disclose the method of claim 1, and Agensys further discloses wherein the subject has locally advanced or metastatic cancer (paragraphs [0118), [0424), [04261).
Claims 49 and 52 cover effective amounts and treatment regiments. However, the amount of the recited ADC in the disclosed composition is a result-effective parameter that will affect the pharmacological and pharmacokinetic properties of the final composition. In this manner, the amount of a specific ingredient in a composition is clearly a result-effective parameter that a person of ordinary skill in the art would routinely optimize.
Specifically, it would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve a desired result. For any compound, the therapeutically effective dose can be estimated initially either in cell culture assays or in animal models, usually rats, rabbits, dogs, or pigs. The animal model also can be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans.
Therapeutic efficacy and toxicity, e.g., ED50 (the dose therapeutically effective in 50% of the population) and LD50 (the dose lethal to 50% of the population), can be determined by standard pharmaceutical procedures in cell cultures or experimental animals. The dose ratio of toxic to therapeutic effects is the therapeutic index, and it can be expressed as the ratio, LD50/ED5o. Pharmaceutical compositions which exhibit large therapeutic indices are preferred. The data obtained from cell culture assays and animal studies is used in formulating a range of dosage for human use. The dosage contained in such compositions is preferably within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage varies within this range depending upon the dosage form employed, sensitivity of the patient, and the route of administration. The exact dosage will be determined by the practitioner, in light of factors related to the subject that requires treatment. Dosage and administration are adjusted to provide sufficient levels of the active ingredient or to maintain the desired effect. Factors which can be taken into account include the severity of the disease state, general health of the subject, age, weight, and gender of the subject, diet, time and frequency of administration, drug combination(s), reaction sensitivities, and tolerance/response to therapy. Long-acting pharmaceutical compositions can be administered once or twice daily every 3 to 4 days, every week, or once every two weeks depending on the half-life and clearance rate of the particular formulation.
Normal dosage amounts can vary from micrograms to 100,000 micrograms, up to a maximum total dose, depending upon the route of administration. Guidance as to particular dosages and methods of delivery is provided in the literature and generally available to practitioners in the art.
Moreover, optimal drug regiments are also result-effective parameters that will affect the therapeutic value of the recited composition and are thus also subject to optimization.
In this way, optimization of these parameters is a routine practice, and consequently, would be prima facie obvious, absent factual evidence demonstrating an unexpected benefit of the claimed amount(s).
The rejected claims cover treatment of cancers or not specifically taught by the primary and secondary references and/or treatment of subjects that have previously received traditional therapies of these types of cancers. However, antibody-drug conjugates (ADCs) offer benefits in cancer therapy beyond traditional chemo-, hormone- and immune checkpoint-therapies by selectively targeting cancer cells and delivering potent cytotoxic drugs directly to cancer cells, increasing effectiveness and reducing side effects compared to traditional chemotherapy. This targeted delivery improves the "therapeutic index" by increasing drug concentration in the tumor while decreasing it in healthy tissues, see Diamantis (“Antibody-drug conjugates (ADCs) are an emerging novel class of anticancer treatment agents that combines the selectivity of targeted treatment with the cytotoxic potency of chemotherapy drugs. New linker technology associated with novel highly potent cytotoxic payloads has permitted the development of more effective and safe ADCs. In recent years, two ADCs have been licensed, T-DM1 and brentuximab vedotin, and are already establishing their place in cancer treatment. A plethora of ADCs are being investigated in phases I and II trials, emerging data of which appears promising. As we deepen our understanding of what makes a successful ADC, an increasing number of ADCs will likely become viable treatment options as single agents or in combination with chemotherapy. This review will present the philosophy underlying ADCs, their main characteristics and current research developments with a focus on ADCs in solid tumours.”).
In this way, those of ordinary skill could have applied the instant ADC’s in the manner required and in a predictable fashion for the purposes of treating the recited cancers and treatment of subjects that have previously received traditional therapies of these types of cancers. As outlined above, the primary and secondary references teach treating cancers with anti-191P4D12 (MMAE) ADC’s. Diamantis is added for the proposition that these types of conjugates are applicable to treating the recited cancers or treating of subjects that have previously received traditional therapies. Specifically, Diamantis teaches the particular known technique of using ADC’s an alternate therapy for treating cancers 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 the recited cancers would have yielded predictable results. Accordingly, using the instant anti-191P4D12 (MMAE) ADC’s to treat the recited cancers and treatment of subjects that have previously received traditional therapies of these types of cancers would have been prima facie obvious.
Claim 46 is rejected under 35 U.S.C. 103 as being unpatentable over obvious over US 20150306245 A1 (hereinafter “Agensys”) in view of Rajc et al., Pathology - Research and Practice. 2017, Vol. 213, No. 9, pages 1102-1108 (hereinafter “Rajc”) in further view of Diamantis et al., British Journal of Cancer (2016) 114, 362–367 (hereinafter “Diamantis”) in further view of Chen et al., Determination of Drug-to-Antibody Ratio for Antibody-Drug Conjugates Purified from Serum, Agilent Technologies, pp. 1-9, 2016 (Agilent).
Claim 46 requires specific drug-antibody ratios (DAR) that may not be specifically taught by the primary or secondary references.
However, there are a limited and finite number of DAR’s for a given antibody- drug conjugate (ADC), around 8. The prior art demonstrates that optimization of the DAR is a critical part of ADC development, since the DAR value affects the efficacy of the drug, as low drug loading reduces the potency, while high drug loading can negatively affect pharmacokinetics (PK)1 and toxicity. At the time the invention was
made, easy, accurate and reproducible DAR calculation of ADC’s was within the
purview of those of ordinary skill, see Agilent:
PNG
media_image3.png
436
440
media_image3.png
Greyscale
In this manner, it would have been obvious to one have ordinary skill in the art at the time that applicant’s inventions was made to have made ADC’s with the recited DAR with a reasonable expectation that the resulting ADC with a DAR of 2 would be useful in treating cancer. In this connection, it is well-settled that ADC’s with a DAR from 1-8 are well within the purview of those of ordinary skill; and it would have been obvious to one of ordinary skill in the art at the time the invention was made to choose from this finite number of DAR options with a reasonable expectation of success of producing a ADC functional with a functional DAR.
Specifically, it is well within the skill of the artisan to try any of the 1-8 DAR’s. As outlined above, a DAR value affects the efficacy of the drug, as low drug loading reduces the potency, while high drug loading can negatively affect pharmacokinetics (PK)1 and toxicity. Here, a skilled chemist at the time would simply make the known ADC’s of the known 8 DAR’s. Indeed, it would have been part and parcel to make the different DAR’s to find one that is pharmaceutically acceptable. Therefore, the applied references provide ample reason to make the recited ADC’s with a DAR in the required range.
With regard to any unpredictability associated with the DAR’s, the notion that unpredictability confers patentability in cases of DAR’s of known ADC’s should be disregarded since a rule of law equating unpredictability to patentability, applied in this case, would mean that any new ADC based on a different DAR would be separately patentable, simply because the formation and properties of each ADC must be verified through testing. This cannot be the proper standard since the expectation of success need only be reasonable, not absolute.
Here, the references provide the reasonable expectation of success, as outlined above. Namely, the references demonstrate the reasonable expectation of success since the references sufficiently characterize the instant ADC’s including the required heavy and light chains, see above. With regard to any alleged unexpected property possessed by those ADC’s with a specific DAR, it is error to assume that any superior property is unexpected, especially in the instant case, where the pharmacodynamic and pharmacokinetic properties of different DAR’s are not predictable. In this case, given the range of possible DAR’s, one skilled in the art would expect different DAR’s to provide ADC’s having a range of properties, some of which would be superior, and some of which would be inferior.
Rather, Applicant has conducted a common optimization of the known DAR’s to produce the claimed ADC, which is routine. Specifically, Applicant engaged in routine, verification testing to optimize selection of one of several known and clearly suggested DAR’s to prepare a pharmaceutically-acceptable conjugate. In this regard, creating a “product or process that is more desirable, for example because it is stronger, cheaper, cleaner, faster, lighter, smaller, more durable, or more efficient . . . to enhance commercial opportunities . . . is universal—and even common-sensical.” see DyStar Textilfarben GmbH v. C.H. Patrick Co., 464 F.3d 1356 at 1368. Therefore, the recited ADC’s with the recited DAR ‘s obvious, since DAR’s are routine and prima facie obvious.
Applicant argues that the claims have been amended to recite that the subject has locally advanced or metastatic head and neck cancer; and wherein:
(i) the subject has progressed or relapsed following a platinum-based therapy;
and/or
(ii) the subject has previously received a therapy with an inhibitor of programmed cell death protein-1 (PD-1) or an inhibitor of programmed cell death-ligand 1 (PD-L1).
However, as outlined above, Diamantis is added for the proposition ADC’s, as disclosed by the applied references, are applicable to treating the recited cancers or treating of subjects that have previously received traditional therapies. Specifically, Diamantis teaches the particular known technique of using ADC’s an alternate therapy for treating cancers was recognized as part of the ordinary capabilities of one skilled in the art, therefore providing a reasonable expectation of success.
Any alleged unexpected result is not commensurate across the entire scope of ADC’ claimed.
The double patenting rejections are maintained:
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, 25, 35, 38, 41, 42, 44, 46, 49, 52, 57-59 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No.12257340 in view of Rajc, Diamantis and Agilent.
Although the claims at issue are not identical, they are not patentably distinct from each other. Specifically, the conflicting claims recite methods of treating cancer with anti-191P4D12 (MMAE) ADC’s which anticipate those methods of treating recited by the rejected claims. Alternatively, the difference between the methods covered in the rejected claims and those covered by the conflicting claims is that the conflicting claims may not recite the instant methods 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 elements of the instant methods 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).
Nonetheless, Rajc, Diamantis and Agilent are applied for the proposition that the recited subject has hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer; and treatment of cancers or not specifically taught by the primary and secondary references and/or treatment of subjects that have previously received traditional therapies of these types of cancers; and the required DAR’s are within the purview of those of ordinary skill, and thus prima facie obvious, as outlined above.
Moreover, the conflicting claims may recite conjugates, whereas the rejected claims recite methods of treating. However, the specification of the conflicting patent discloses the utility of the recited conjugates as covered by the instant methods of using the conjugates, see Sun Pharmaceutical Industries, Ltd., v. Eli Lilly and Co. where the district court ruled that the claims of the ‘826 patent were invalid in light of the ‘614 patent which disclosed gemcitabine’s use in cancer treatment, but did not claim it. In making this ruling, the district court relied on the Federal Circuit’s earlier rulings on double patenting of compound claims, mainly Geneva Pharmaceuticals, Inc, v. GlaxoSmithKline PLC, 349 F. 3d 1373 (Fed. Cir. 2003), and Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc., 518 F.3d 1353 (Fed. Cir. 2008). In both of these cases, the Federal Circuit found claims of a later patent invalid for obviousness-type double patenting where an earlier patent claimed a compound, disclosing its utility in the specification, and a later patent claimed a method of using the compound for a use described in the specification of the earlier patent. The cases also established that in determining the scope of the conflicting conjugate claims for a double patenting rejection one must look to the specification to interpret the utility of the conjugates.
Claims 1, 25, 35, 38, 41, 42, 44, 46, 49, 52, 57-59 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 9314538 in view of Rajc, Diamantis and Agilent.
Although the claims at issue are not identical, they are not patentably distinct from each other. Specifically, the conflicting claims recite methods of treating cancer with anti-191P4D12 (MMAE) ADC’s which anticipate those methods of treating recited by the rejected claims. Alternatively, the difference between the methods covered in the rejected claims and those covered by the conflicting claims is that the conflicting claims may not recite the instant methods 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 elements of the instant methods 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).
Nonetheless, Rajc, Diamantis and Agilent are applied for the proposition that the recited subject has hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer; and treatment of cancers or not specifically taught by the primary and secondary references and/or treatment of subjects that have previously received traditional therapies of these types of cancers; and the required DAR’s are within the purview of those of ordinary skill, and thus prima facie obvious, as outlined above.
Moreover, the conflicting claims may recite conjugates, whereas the rejected claims recite methods of treating. However, the specification of the conflicting patent discloses the utility of the recited conjugates as covered by the instant methods of using the conjugates, see Sun Pharmaceutical Industries, Ltd., v. Eli Lilly and Co. where the district court ruled that the claims of the ‘826 patent were invalid in light of the ‘614 patent which disclosed gemcitabine’s use in cancer treatment, but did not claim it. In making this ruling, the district court relied on the Federal Circuit’s earlier rulings on double patenting of compound claims, mainly Geneva Pharmaceuticals, Inc, v. GlaxoSmithKline PLC, 349 F. 3d 1373 (Fed. Cir. 2003), and Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc., 518 F.3d 1353 (Fed. Cir. 2008). In both of these cases, the Federal Circuit found claims of a later patent invalid for obviousness-type double patenting where an earlier patent claimed a compound, disclosing its utility in the specification, and a later patent claimed a method of using the compound for a use described in the specification of the earlier patent. The cases also established that in determining the scope of the conflicting conjugate claims for a double patenting rejection one must look to the specification to interpret the utility of the conjugates.
Applicant again argues that the claims have been amended to recite that the subject has locally advanced or metastatic head and neck cancer; and wherein:
(i) the subject has progressed or relapsed following a platinum-based therapy;
and/or
(ii) the subject has previously received a therapy with an inhibitor of programmed cell death protein-1 (PD-1) or an inhibitor of programmed cell death-ligand 1 (PD-L1).
Again, Diamantis is added for the proposition ADC’s, as disclosed by the applied references, are applicable to treating the recited cancers or treating of subjects that have previously received traditional therapies. Specifically, Diamantis teaches the particular known technique of using ADC’s an alternate therapy for treating cancers was recognized as part of the ordinary capabilities of one skilled in the art, therefore providing a reasonable expectation of success.
Any alleged unexpected result is not commensurate across the entire scope of ADC’ claimed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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 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.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646
Prosecution Insights