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 amendment and argument of 7/13/26 are entered.
Claims 7, 16-17, and 28 are amended.
Claims 23, 25, 32, and 34 are canceled.
Claims 7-22, 24, 26-31, 33, and 35-36 are pending and are considered herein.
Claim Status, Canceled Claims
In light of the cancelation of Claims 23, 25, 32, and 34, all rejections and objections thereto, are withdrawn.
Claim Rejections - 35 USC § 112
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.
In light of the amendment, canceling the Markush of nested ranges, the rejection of Claim 16 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, is withdrawn.
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.
In light of the acceptance of the terminal disclaimer against U.S. Patent No. 11,642,384, all rejections for double patenting against the same, are withdrawn.
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.
In light of the amendments, requiring a promoter, the rejections of Claims 17-24, 26-33, and 35-36 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, are withdrawn
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.
In light of the removal of SPINK3, SPINK10, SPINK11, and SPINK12, the rejections of Claims 17-22, 24-31, and 33-36 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, are withdrawn.
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.
While the rejections for written description are withdrawn (the rejection was meant to be enablement, so the present action is nonfinal):
Claims 7-22, 24, 26-31, 33, and 35-36 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating netherton syndrome with an HSV expressing SKPINK5, administered topically, transdermally, subcutaneously, intradermally, or transmucosally to a subject with a loss-of-function mutation in a SPINK5 gene, does not reasonably provide enablement for the breadth of SPINKs, cross-corrections with distinct spinks, atopic dermatitis or other disorders, and for the breadth of administrations. 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/use the invention commensurate in scope with these claims.
The claims are broad for the SPINK proteins SPINK1, SPINK2, SPINK4, SPINK5, SPINK6, SPINK7, SPINK8, SPINK9, SPINK13, and SPINK14 (specifically listed in Claims 17 and 28), in the context of a wide range of delivery methods (e.g., Claims 26-27 and 35-36), and expressing the SPINK protein in any specific tissue, including the cell types listed in Claim 19, and with at least the intents to enhance/increase/augment/supplement the level of the SPINK in one or more cells of a subject, which may also be specifically human (e.g., Claim 18).
The specification teaches the purpose of expressing these SPINK proteins is to treat disorders (e.g., paragraph 149). For example, SPINK 1 is taught to be associated with hereditary pancreatitis (PCTT) and tropical calcific pancreatitis (e.g., Id). SPINK2 is taught to be associated with spermatogenic failure 29 (SPGF29) (e.g., Id.). SPINK5 is taught for Netherton Syndrome (NS) or Atopic Dermatitis (AD) (e.g., paragraph 149). SPINK 4, SPINK6, SPINK7, SPINK8, SPINK9, SPINK 13, and SPINK14 are provided with no associated condition in the specification. Moreover, the cell types (e.g., Claim 19) and SPINK proteins, being separate, indicate that any SPINK may be utilized in any tissue, and thus may be used to treat any other SPINK’s-related conditions.
The brunt of the specification focuses on the treatment of NS with SPINK5 (e.g., TITLE), beyond the mere statements above of associations with each of the specifically described SPINK proteins and their associated disorders.
In the examples Applicant utilized their HSV-S5 vector, which was screened to be the highest SPINK5 producing virus in Vero cells (examples). The transgene in this case was codon-optimized, and there was no demonstration that non-codon optimized would produce any comparable levels of SPINK5. The specification teaches this codon-optimized version increases the stability and/or yield in the target cell (paragraph 57). At paragraph 251, it is noted that the expression, from HSV-S5 can produce secretion from keratinocytes at therapeutically-relevant levels.
Following this, it is noted that BALB/c mice were used, as SPINK5-/- is neonatal lethal
in animals (paragraph 249), and teaches treatment of the mice by topical administration post-
abrasion, and intradermally (paragraph 251-252). From this, expression was found in the skin.
However, it is noted that the art understands that a promoter is needed for expression of
the SPINK5, otherwise the protein (as taught throughout, the important part) is needed for
treatment. With regard to the disorders encompassed, unlike NS, it is well known that many
genes have been linked to AD (Bauer (2017) “Atopic Eczema: Genetic Associations and
Potential Links to Developmental Exposures”, International Journal of Toxicology, 36(3): 187-
98). Thus, the Artisan would not know which of the group with AD would be treatable with
SPINK5 expression.
With regard to SPINK 4, SPINK6, SPINK7, SPINK8, SPINK9, SPINK 13, and SPINK14, the Art does not recognize any gene therapy with these genes, to treat any specific disease. In fact, SPINK4 is associated with several cancer types, including colorectal cancer (Kazanjian, et al (2010) “Atonal Homolog 1 Is Required for Growth and Differentiation Effects of Notch/[gamma]-Secretase Inhibitors on Normal and Cancerous Intestinal Epithelial Cells” Gastroenterology, 139: 918-28, e.g., p. 920, col. 2). Thus, the Artisan would not predict any therapy with this gene. Moreover, such does not even show a cause-and-effect, so it is not even predicted to produce cancer. Similar arguments may be made with the other SPINK proteins. For example, SPINK1 at the time of invention, was associated with cancers (e.g., Rasanen, et al. (2016) “Emerging Roles of SPINK1 in Cancer”, Clinical Chemistry, 62(3): 449-57, ABSTRACT). More, SPINK2 was known to be associated with pancreatitis (e.g., Petersen (2017) “Familial Pancreatic Cancer”, Siminal Oncology, 43(5): 548-53, p. 549, last paragraph). SINK4 was not known to be be associated with more than as a marker in bladder cancer (e.g., Goldstein, et al. (2017) “Genomic Activation of PPARG Reveals a Candidate Therapeutic Axis in Bladder Cancer”, Cancer Research, 77: 6987-98, p. 6992, col. 1, paragraph 3). SPINK6 is known to be affected by Gingipains of Porphyromonas gingivalis, but no cause and effect is known for any disorder but the Gingipains may control SPINK6 (e.g., Plaza, et al. (2016) “Gingipains of Porphyromonas gingivalis Affect the Stability and Function of Serine Protease Inhibitor of Kazal-type 6 (SPINK6), a Tissue Inhibitor of Human Kallikreins”, Journal of Biological Chemistry, 291(36): 18753-64, ABSTRACT). While SPINK7 appears to serve ans an inhibitory checkpoint for esophageal epithelial inflammatory responses (Azouz, et al. (2018) “The antiprotease SPINK7 serves as an inhibitory checkpoint for esophageal epithelial inflammatory responses”, Science Translational Medicine, 10(444)eaap9736, 14 pages long, ABSTRACT), demonstrating no specific disorder to treat. The examiner was unable to find a single thing associated with SPINK8 known at the time of filing. SPINK9 is associated with non-palmoplantar skin, but the state of the art only recognized that it “may” play a role in various cascades in the tissue, not that it would treat anything (e.g., Brattsand, et al. (2009) “SPINK9: A Selective, Skin-Specific Kazal-Type Serine Protease Inhibitor” Journal of Investigative Dermatology, 129: 1656-65, ABSTRACT). SPINK13 is associated with sperm maturation, but the Art still had not developed to the point to know therapy could be affect3ed, but instead, it expects that further study will provide SPINK13 as a putative target for male contraceptives (e.g., Ma, et al. (2013) “Spink13, an Epididymis-specific Gene of the Kazal-type Serine Protease Inhibitor (SPINK) Family, Is Essential for the Acrosomal Integrity and Male Fertility” The Journal of Biological Chemistry, 288(14): 10154-65, ABSTRACT). The Examiner found no disease associated with SPINK14. Thus, the diseases not known in a cause-and-effect relation, such that it would be predicted that increasing the production in those cells would treat anything, or if the lowered level is an effect of the disease, rather than causative. Moreover, in some SPINKs it is not even known to be associated with any specific disease.
With regard to cross-correction (i.e., the SPINK protein Markush claim is separately depending from the independent claims, from the methods of administration claims, and they are both separately depending from the independent claim from the cells affected). Each of the SPINK proteins may be a SPINK protein, but their specificities are distinct, and thus, one SPINK’s deficiency would not be predicted to be treatable by way of another SPINK’s expression. For example, while SPINK1 targets trypsins (e.g., Granda, et al. (2023) “Inhibition of mouse trypsin isoforms by SPINK1 and effect of human pancreatitis-assocaited mutations”, Pancreatology, 23: 358-366, ABSTRACT), SPINK5 targets various serine proteases, primarily Kallikreins (e.g., Furio, et al. (2015) “KLK5 Inactivation Reverses Cutaneous Hallmarks of Netherton Syndrome”, PLOS Genetics, 11(9): e1005389, 20 pages, ABSTRACT). Thus, one SPINK may not be used in another’s tissue or disease. This also emphasizes that the delivery by one route or another would not necessarily transfect the proper target tissue. For example, topical delivery of HSV to the skin, would likely transfect the skin, and such, even if delivering SPINK2 would not necessarily treat spermatogenic failure 29.
With regard to SPINK5 and atopic dermatitis, the specification states the studies were performed in BALB/c mice as there is no practical disease model for spink5 deficiency. Desargues, et al. (2005) “SPINK5-deficient mice mimic Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity” Nature Genetics, 37: 56-65, teaches SPINK5-/- mice faithfully replicate the key features of NS (ABSTRACT). Thus, the Artisan would see that NS could be so treated. However, in atopic dermatitis, Bauer (2017) “Atopic Eczema: Genetic Associations and Potential Links to Developmental Exposures”, International Journal of Toxicology, 36(3): 187-98, teaches over 30 genes have been linked to AD with the Flg and Tmem79/Matt genes being common (ABSTRACT). Thus, the correlation of treatment for AD is not backed up by the prior art.
Thus, for the vast majority of disorders, the Artisan would have to look to the art and experiment to find a disease associated in many cases, experiment to determine if the relation is cause-and-effect and predicts therapy, determine if the vector can be delivered to the tissue in large enough amounts and expressed in large enough amounts, and determine if it will treat the disease by way of direct action or and cross-corrective methods for other SPINK deficiencies, and lastly, determine if it will not instead cause cancer or other disorders by overexpression of the protein in each case.
Such is considered undue experimentation as it is required for the vast majority of embodiments encompassed, and thus, the claims are not enabled for other than the scope specifically provided in the initial paragraph.
Response To Argument – Enablement
Applicant’s argument of 7/13/26 is accepted and the rejection is changed to enablement, as the form paragraph was the incorrect one. However, as best can be translated, the arguments are answered in terms of enablement.
Applicant argues that claim 7 is to limited and not properly part of the rejection (p. 9, paragraph 3), and that the rejection is enablement, while the form paragraph is written description.
Such is persuasive. Claim 7, and depending claims are withdrawn from the rejection, and an enablement is provided for the other sets of claims.
Applicant argues the description and codon optimized sequences (pp. 9-11).
Such is persuasive. The rejection was never on codon optimized sequences. It was a review of the disclosure.
Applicant argues that undue experimentation is enablement, again, and argues that the rejection is incorrect, arguing the sequences are disclosed (pp. 11-12).
Such is persuasive. The form paragraph was incorrect.
Applicant argues that it is not proper to import claim limitations from the specification in to the claims, and that the claims are not to treatments (p. 12, last paragraph).
Such is not persuasive. Doing it just to do it has no utility, much less enablement. Here, the only purpose for performing these methods is to treat disease.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT M KELLY whose telephone number is (571)272-0729. The examiner can normally be reached M-F: 8a-5p.
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ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638
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