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 .
Claims 7-36 are pending as amended 3/24/23, and are considered herein.
Formalities:
The drawings of 3/22/23 are accepted.
The specification of 3/22/23 is accepted.
The IDS filings of 9/9/23 (two filings), 2/12/24, and 9/24/24 have been considered for their references therein, and is provided herewith signed by the Examiner to indicate consideration.
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.
Claim 16 is 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 16 recites the broad recitation “at least 80% … sequence identity”, and the claim also recites “at least 85%, at least 90%, … or 100% sequence identity” which are the narrower statements of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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 7-10 and 12-36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,642,384. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claims 7 and 17: Patent Claim 1 teaches a pharmaceutical composition of the same HSV encoding SPINK5 and an excipient. Claim 7 teaches formulation for several forms of administration, matching the present claims administration forms. The whole purpose for making this pharmaceutical composition is for treating NS or AD (e.g., TITLE; paragraph bridging pages 57-58). Thus, it would be obvious to administer the same to treat NS or AD, through these form of administration. The Artisan would do so and expect it to work, as it is a claimed pharmaceutical patented just for this purpose.
Claim 8: Claim 4 teaches to use the human SPINK5, which indicates intent to treat humans.
Claim 9: These symptoms of NS are present in NS, and thus, are necessarily treated when treating NS.
Claim 10: These symptoms are present in AD, and thus, it would necessarily be treated in such methods of administering the pharmaceutical compositions.
Claims 12 and 20: Claim 2 teaches HSV-1 genome.
Claims 13 and 21: Claim 3 teaches the same inactivating mutation Markush.
Claims 14 and 22: Claim 6 teaches inactivating mutations in one or both ICP4 genes.
Claims 15 and 23-24: Claim 4 teaches human SPINK5.
Claim 16: Claim 5 teaches the same identities to the same sequence identifiers.
Claim 18: Humans suffer from NS and AD, and thus, it would be obvious to treat them, as that is the purpose of the compositions.
Claim 19: Claim 7 teaches topical administration and such would necessarily deliver the to the skin cells including keratinocytes.
Claim 25: Claim 1 teaches the promoter, operably linked.
Claims 26-27: Claim 7 teaches several of the same formulations for these types of administration.
Claims 28 and 34: Claim 1 recites a pharmaceutical composition comprising a replication defective HSV comprising a sequence encoding SPINK5 operatively linked to a promoter suitable for transcription in a mammal cell, and a pharmaceutically acceptable excipient.
Claim 29: Claim 2 is to an HSV-1 genome.
Claim 30: Claim 3 teaches an inactivating mutation in the same Markush of coding regions.
Claim 31: Claim 6 teaches an inactivating mutation in one or both copies of ICP4.
Claim 32: Claim 1 teaches SPINK5.
Claim 33: Claim 4 teaches human SPINK5.
Claim 35-36: Claim 7 teaches several formulation forms for the same route of administration.
Thus, in light of the patent, the invention is obvious. The Artisan would do so as it is claimed, and a pharmaceutical composition taught specifically for treating NS and AD, as the essential written description for such pharmaceutical compositions. The Artisan would expect success, as it is claimed and specifically for treating these disorders.
Claims 7-36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,642,384 in view of Brown, et al. (2006) “Dermal and Transdermal Drug Delivery Systems: Current and Future Prospects”, Drug Delivery, 13: 175-87.
As shown above, the various claims are obvious over the base patent alone, however, the aspect of abrading the skin, prior to administration is not taught.
However, the Artisan, interested in topical delivery, would be aware of Brown. Brown teaches the use of abrasion to deliver drugs across the skin barrier (transdermal delivery) (Abstract; paragraphs bridging pages 180-81).
Thus, in light of the patent and Brown, the Artisan would have found it obvious to abrade the skin prior to administration. The Artisan would do so because it increases the permeability of the skin protective layer to get into the skin. The Artisan would expect success, as it is utilized for art-recognized purposes.
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 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. 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 claims, as seen by non-rejected claims 7-17, 25, and 34, are generic to methods of treatment (17 and depending) and pharmaceutical compositions (28 and depending), to herpes simplex viruses comprising merely a coding sequence for a SPINK protein.
The whole of the specification teaches that the encoded SPINK protein must be transcribed and translated, so that the SPINK protein is expressed and present to treat the subject. Claim 17 indicates the SPINK protein itself must be increased/enhanced/etc., in level of the SPINK of protein. This goes for the pharmaceutical compositions, too, as they must be efficacious in the treatment intended in order to be pharmaceutical compositions.
For the compositions: It should be noted that the composition claims are limited by the specification, to pharmaceutical compositions which are in such form as to permit the biological activity of the active ingredient(s) to be effective (paragraph 49), and axiomatically, to be effective an effective amount must necessarily be administered, and the specification states that the “effective amount” is at least the amount to affect a measurable improvement or prevention of one more symptoms of a particular disorder (paragraph 50).
The specification teaches, throughout, that the compositions utilized (i.e., the herpes vectors encoding the SPINK protein), must express the SPINK in order to increase the levels and exhibit a therapeutic effect on the subject (e.g., paragraph 21 and the examples). It is taught to operably link promoters to the coding sequence to effect its transcription (paragraph 43). Also mentioned is the generic “regulatory sequence”, but the same is taught only in context of promoters (e.g., paragraph 44). Other known regulatory sequences may include enhancers, etc., but these all require a promoter to effect the efficient transcription of the coded sequence. Paragraph 83 exemplifies many promoters, and talks about other components, but each of these is known to still require a promoter to effect efficient transcription of the coded sequence. I.e., it is clear that the promoter is always required from the specification.
The Art recognizes the use of promoters for the transcription of a DNA encoded sequence, and does not recognize the simple use of enhancer or other element to effect its transcription.
Thus, the Artisan would not recognize Applicant to be in possession of HSV encoding SPINK protein(s) without an operably linked promoter, either in the methods, or in the compositions themselves.
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 17-22, 24-31, and 33-36 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. 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 claims, as seen by dependent claims 23 and 32 are generic for SPINK3, SPINK10, SPINK11, and SPINK12. I.e., there are 14 SPINK proteins, and Claims 23 and 32 claim all of the SPINK proteins as a Markush, meaning that the rejected claims are generic for SPINK3, SPINK10, SPINK11, and SPINK12.
However, the specification provides no antecedent basis, much less description of SPINK3, SPINK10, SPINK11, and SPINK12. The purpose of the SPINK coding sequence, is taught throughout the specification, for the purpose of increasing SPINK protein production in the cells (e.g., paragraph 113). And the production thereof is meant to improve symptoms of specific conditions. For example, SPINK5 is taught for NS and AD (TITLE, paragraph 149), while SPINK1 is linked with PCTT (Id.). On the other hand, the Artisan is left with the prior for reasons to treat conditions with SPINK3, SPINK10, SPINK11, and SPINK12.
The Art however, teaches that SPINK3 is associated with increased efficacy of cancers (e.g., Tiwari, et al. (2015) “SPINK1 promotes colorectal cancer progression by downregulating Metallothioneins expression”, Oncogenesis, 4: e162, 12 pages, TITLE). Official notice is taken to say that it also increases the chemoresistance of breast cancer. However, no specific treatment is taught in the art in how to treat it with SPINK1 without causing/potentiating cancers, which could kill the subject before any beneficial effect is had. Thus, the compositions and methods would, at best, be for the purpose of seeing what happens, which lacks utility, much less description.
With regard to another of the generic SPINKs addressed herein, SPINK10 is associated with being downregulated in the sciatic nerve in diabetic mice (e.g., Gu, et al. (2018) “Differential gene expression profiling of the sciatic nerve in type 1 and type 2 diabetic mice”, Biomedical Reports, 9(4): 291-304, TABLE SIII).
Thus, given the associations with negative effects that might kill the subject before any beneficial effect is seen, and lack of knowledge of cause-and-effect for these generic SPINK proteins in the Art, the Artisan would not have understood Applicant to have been in possession of the generic SPINK protein is presently claimed.
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 7-36 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. 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 claims are broad for the SPINK proteins SPINK1, SPINK2, SPINK4, SPINK5, SPINK6, SPINK7, SPINK8, SPINK9, SPINK13, and SPINK14 (e.g., specifically listed in Claims 23 and 32), in the context of a wide range of delivery methods (e.g., Claims 26-27), and expressing the SPINK in any specific tissue, including the cell types listed in Claim 19.
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 252), and teaches treatment of the mice by topical administration post-
abrasion, and intradermally (paragraph 255). 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. They are 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.
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.
Thus, for the vast majority of disorders, the Artisan would have to look to the art and would often find no specific causative relation between any specific SPINK and disorder, and would have to test for cross-correction, delivering to different tissues, and use of distinct SPINKS to treat any specific disorder by way of raising the amount of any specific SPINK in any specific tissue.
Such is considered undue experimentation as it is required for the vast majority of embodiments encompassed.
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