DETAILED ACTION
Claim 1 is pending in this application. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . An action on the merits follows.
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.
Claim 1 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for 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.
Claim 1 recites a method which utilizes a genetically modified population of Drosophila whose genome comprises a first promoter sequence activated by a first stressor coupled to a first target sequence corresponding to a first target compound.
The as filed specification does not provide sufficient written description for the genus of promoters activated by any “stressor” other than a heat shock promoter. The specification does not specifically define what constitutes a “stressor” but provides examples of particular stressors in paragraphs 12 and 39 of the instant specification which include heat-shock, cold-shock, UV exposure, dehydration, and nutrient-deficiency. The specification provides only a limited description of the genetic modification of flies, and in particular, Drosophila, in which a transgene comprising a nucleic acid sequence encoding a target polypeptide is operatively linked to a promoter/regulatory element inducible by an environmental “stressor”. The specification does disclose a heat inducible promoter which is an HSP70 promoter combined with an HSP70 5’UTR. The specification does not teach or identify any promoter, 5’UTR, or other regulatory elements other than the HSP70 promoter and 5’UTR, which is/are capable of being induced by any “stressor” other than heat in any insect species including Drosophila. It is further noted that the specification does not provide any working examples of the disclosed invention.
As set forth in MPEP 2163:
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings.
An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). "Compliance with the written description requirement is essentially a fact-based inquiry that will ‘necessarily vary depending on the nature of the invention claimed.’" Enzo Biochem, 323 F.3d at 963, 63 USPQ2d at 1612.
In regards to the written description requirement for genuses, MPEP 2163 states:
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 (see i)(A) above), reduction to drawings (see i)(B) above), 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 i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014)
While the claims recite the use of a genus of promoters “activated by a stressor”, the applicant has not provided any description or reduction to practice of any species within the genus other than a Drosophila fly whose genome has been modified to include a transgene comprising a nucleic acid sequence encoding a target polypeptide, and optionally a marker polypeptide, operatively linked to an HSP70 heat shock promoter and HSP70 5’UTR, which is inducible by an increase in heat. The disclosure of this single species of promoter is not sufficient to reflect the variation within the genus of promoters “activated by any stressor” as claimed, particularly as the specification does not disclose any known or disclosed correlation between function and structure of the HSP70 heat shock promoter and any other promoter which is inducible by other stressors such as cold, nutrient deficiency, or UV exposure. Further, the prior art does not teach the use of additional stress-inducible promoters/regulatory elements in Drosophila flies, or teach that inducible production of recombinant polypeptide in insects mediated by cold-shock, UV exposure, dehydration, and nutrient deficiency was well known or well established at the time of filing. Akmammedov et al., for example, reviews the state of the art for inducible transgenic expression systems and associated problems in Drosophila circa 2017 (Akmammedov et al. (7/31/17) Scientific Reports, Vol. 7:6899.DOI:10.1038/s41598-017-07282-w, pages 1-12). Akmammedov et al. teaches that the state of the art for inducible expression is Drosophila is largely based on polypeptide or chemical induction (doxycycline/tetracycline or GAL4) of the activity of a promoter operably linked to the transgene of interest, or the use of heat shock- where the transgene is operably linked to a heat shock inducible promoter such as HSP70 (Akmammedov et al., Table I). Beech et al., in a broader review of transgenic insects, teaches that while a number transgenic insects other than Drosophila flies had been made at the time of filing, such as species of mosquitoes or silkworms, the use of such insects for protein production was mostly speculative and at the earliest stage of development (Beech et al. (2012) Collection of Biosafety Reviews, Vol. 6, 66-124, see pages 81-83). Beech et al. further does not teach the use of inducible gene expression in non-Drosophila transgenic insects or the use of any “stressors” for inducing gene expression in transgenic insects. Thus, the state of the prior does not establish that “stressor” induced protein expression in transgenic insects including Drosophila was either well known or well developed at the time of filing.
Therefore, based on the limited description provided in applicant's specification as discussed in detail above for the genus of promoters capable of stressor induced production of a target compound in a Drosophila, and the undeveloped stated of the prior art with respect to “stressor” induced expression of proteins in transgenic insects including Drosophila, the skilled artisan cannot envision the detailed chemical structure of the transgenic Drosophila or the inserted stressor inducible transgenes as defined by the specification or the detailed chemical structure of the genus of promoters/regulatory sequences activatable by any stressor encompassed by the claims. As such, the specification does not demonstrate that applicant was in possession of and/or had reduced to practice the generic invention as claimed. Applicant is reminded that adequate written description requires more than a mere statement that it is part of the invention. See Fiers v. Revel, 25 USPQ2d 1602 at 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Thus, for the reasons outlined above, claim 1 does not meet the requirements for written description under 35 U.S.C. 112, first paragraph.
Claim 1 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for 1) a method for heat induced polypeptide production in a Drosophila fly comprising providing a population of transgenic Drosophila flies whose genome comprises a transgene comprising an HSP70 promoter and an HSP70 5’UTR operably linked to a nucleic acid sequence encoding a polypeptide of interest, cultivating the population of transgenic Drosophila, exposing the population of transgenic Drosophila to at least 37OC for a period of time sufficient to induce expression of the polypeptide of interest, estimating the concentration of the polypeptide of interest based on detection of the fluorescent or bioluminescent compound, the either A) harvesting the population of transgenic Drosophila if the estimated concentration of the target compound is above the threshold concentration, homogenizing the Drosophila to form a homogenized mixture, and separating a portion of the mixture which comprises the polypeptide of interest from a portion of the mixture which does not comprise the polypeptide of interest, or B) applying a second dose of the heat stressor if the estimated concentration of the target compound is below the threshold concentration until the concentration of the first target compound is above the threshold concentration, does not reasonably provide enablement for providing or generating any population of transgenic Drosophila capable of expressing any target compound wherein exposure of the transgenic Drosophila to any “stressor” result in production/expression of a target compound by the transgenic Drosophila. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
Claim 1 recite a method which utilizes a genetically modified population of Drosophila whose genome comprises a promoter sequence activated by a first stressor coupled to a first target sequence corresponding to a first target compound. The as filed specification does not provide sufficient guidance for the use of promoters associated with any “stressor” other than heat shock. The specification does not define what constitutes a “stressor” but provides examples of particular stressors in paragraphs 12 and 39 of the instant specification which include heat-shock, cold-shock, UV exposure, dehydration, and nutrient-deficiency. In contrast to the breadth of the generic invention, the specification provides only limited guidance for the genetic modification of flies, specifically Drosophila, in which a transgene comprising a nucleic acid sequence encoding a target polypeptide operatively linked to an HSP70 promoter and HSP70 5’UTR, inducible by an environmental “stressor” which is heat, is inserted via a P element into the genome of the Drosophila. The specification does not teach other promoters, 5’UTR, or other regulatory elements, other than the heat inducible HSP70 promoter and HSP 5’UTR, which are capable of being induced by any stressor in Drosophila. It is further noted that the specification does not provide any working examples of the disclosed invention. Thus, while the claims are extremely broad and encompass making and using transgenic Drosophila whose genome comprises one or more promoters selected from an ill-defined number of “stressor” inducible promoters which are induced by at least heat, cold, nutrient deprivation, dehydration, or UV exposure, the specification only provides specific guidance for a single embodiment which is a Drosophila fly whose genome comprises a transgene comprising a heat inducible HSP70 promoter and HSP 5’UTR for driving expression of a target polypeptide.
Further, at the time of filing, inducible protein expression in transgenic insects, including Drosophila, for protein production and purification was not considered either well developed or predictable. Akmammedov et al., for example, reviews the state of the art for inducible transgenic expression systems and associated problems in Drosophila circa 2017 (Akmammedov et al. (7/31/17) Scientific Reports, Vol. 7:6899.DOI:10.1038/s41598-017-07282-w, pages 1-12). Akmammedov et al. teaches that the state of the art for inducible expression is Drosophila is largely based on polypeptide or chemical induction (doxycycline/tetracycline or GAL4) of the activity of a promoter operably linked to the transgene of interest, or the use of heat shock- where the transgene is operably linked to a heat shock inducible promoter such as HSP70 (Akmammedov et al., Table I). Further, neither Akmammedov et al. nor the prior art as a whole at the time of filing teaches inducible gene expression in Drosophila using promoters responsive to cold, nutrient deficiency, dehydration, or UV exposure. Beech et al., in a broader review of transgenic insects, teaches that while a number transgenic insects including Drosophila flies had been made at the time of filing, the use of such insects for protein production was mostly speculative and at the earliest stage of development (Beech et al. (2012) Collection of Biosafety Reviews, Vol. 6, 66-124, see pages 81-83). Beech et al. further does not teach the use of inducible gene expression in transgenic insects based on the use of any non-heat “stressors” for inducing gene expression including UV light. Thus, the state of the prior does not establish that “stressor” induced protein expression within the genus of transgenic insects was either well known or well developed at the time of filing, with the exception of heat-shock induced gene expression in Drosophila using the HSP70 promoter.
Therefore, in view of the art recognized underdeveloped and unpredictable nature of “stressor” induced protein expression in transgenic insects including Drosophila at the time of filing, the lack of guidance provided by the specification for expression regulatory elements such as promoters capable of being activated by any “stressor” in a Drosophila other than the heat inducible HSP70 promoter, the lack of any working examples, and the breadth of the claims, it would have required undue experimentation to practice the breadth of the instant method as claimed in claim 1.
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.
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,991,994, hereafter referred to as the ‘994 patent. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
Claims 1-16 of the ‘994 patent recite essentially the same method as in instant claim 1 with the exception that the claims of the ‘994 patent re limited to a promoter activated by a stressor comprising heat stress. As such, the ‘994 patent claims represent a species of the broader instant claims which read on the use of any promoter activated by any stressor. It is well established that a species of a claimed invention renders the genus obvious. In re Schaumann, 572 F.2d 312, 197 USPQ 5 (CCPA 1978). As such, the claims of the ‘994 patent render obvious instant claim 1.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/075,362, hereafter referred to as the ‘362 application. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The claims of the ‘362 application recites methods which are a species of the instant broader methods. Comparing independent claim 1 of the ’362 application with instant claim 1, the ‘362 application claim 1 recites a method comprising a similar set of method steps as recited in instant claim 1, with the exception that the step of estimating a concentration of the target compound in comparison to a threshold concentration is recited in dependent claim 12 of the ‘362 application. Further, claim 1 of the ’362 application is limited to a first promoter activated by a heat stressor, which is a species of the broader genus of promoters activated by a stressor as claimed in instant claim 1. It is further noted that the ‘362 application claims contain additional limitations regarding certain aspects of each step of the method which are likewise considered species of the broader method of instant claim 1. It is well established that a species of a claimed invention renders the genus obvious. In re Schaumann, 572 F.2d 312, 197 USPQ 5 (CCPA 1978). As such, the claims of the ‘362 application render obvious instant claim 1.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
No claims are allowed.
Any inquiry concerning this communication from the examiner should be directed to Anne Marie S. Wehbé, Ph.D., whose telephone number is (571) 272-0737. If the examiner is not available, the examiner’s supervisor, Maria Leavitt, can be reached at (571) 272-1085. For all official communications, the technology center fax number is (571) 273-8300. Please note that all official communications and responses sent by fax must be directed to the technology center fax number. For informal, non-official communications only, the examiner’s direct fax number is (571) 273-0737. For any inquiry of a general nature, please call (571) 272-0547.
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Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634
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