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 1/7/26 are entered.
Claims 1, 21, 25, and 33 are amended.
Claims 18-19, 26, 31-32, and 34-35 are canceled.
Claim 36 is newly added.
Claims 1-4, 12-17, 21-25, 27-30, 33, and 35 are pending and considered herein.
Claim Status, Canceled Claims
In light of the cancelation of Claims 18-19, 26, 31-32, and 34-35, all rejections/objections thereto, are withdrawn.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.
Claims 1-2, 12-14, 16-17, and 30 remain/are newly rejected, on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,123,376. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1: Patent Claim 1 teaches treating a human with liver or lung fibrosis, comprising systemic or local administration of allogenic human amnion epithelial cell derived exosomes.
Claim 2: The subject is human in Claim 1.
Claim 12: Claims 1 and 6 teach lung or liver fibrosis.
Claim 13: Claims 1 and 6 teach the steps and treatment of lung fibrosis, and thus, it presumed the same affects reverse lung fibrosis and suppression of primary lung fibroblasts.
Claim 14: Claim 3 teach miRNAs affecting the same pathways.
Claim 16: Claim 5 teaches the bank of lyophilized exosomes from immortalized amniotic epitheilal cell line.
Claim 17: Claim 4 teaches the bank of cell lines, and Claim 5 teaching the bank of amniotic epithelial cell lines from which the exosomes are derived, makes it clear that it can be so-derived.
Claim 30: the claims are to liver and lung fibroses (Claims 1 and 6).
Thus, in light of the patent, these claims are obvious. The Artisan would do so, and expect success, as it is claimed.
Claims 1-2, 12-14, 16-17, 21-24 and 30 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,123,376 in view of Popova (2013) “Mechanisms of bronchopulmonary dysplasia”, 7: 119-127, due to amendment.
As shown above, the patent teaches the various elements of the base claims.
Also shown above, the patent teaches treating, e.g., lung fibrosis (Claim 1 and 6), with similar exosomes.
However, the patent does not claim treating BPD.
On the other hand, Popova teaches BPD contains airway fibrosis and interstitial fibrosis (e.g., p. 119, col. 1, paragraph 1).
Claim 21: patent Claims 1 and 6 teach the fibrosis, and the Popova article teaches the fibrosis of the lung.
Claim 22: human is claimed in Claims 1 and 6.
Claim 23: the bank of immortalized bank of human amnion epithelial cell derivation is taught in, e.g., Claim 4.
Claim 24: the bank of lyophilized amniotic exosomes is taught in, e.g., Claim 5.
Thus, in light of the patent and Popova, it would be obvious to treat BPD with the exosomes of the patent. The Artisan would do so, and expect success, as the treatment of fibrosis is claimed, and BPD contains fibrosis in the lung.
Claim 21: patent Claims 1 and 6 teach the fibrosis, and the Popova article teaches the fibrosis of the lung.
Claim 22: human is claimed in Claims 1 and 6.
Claim 23: the bank of immortalized bank of human amnion epithelial cell derivation is taught in, e.g., Claim 4.
Claim 24: the bank of lyophilized amniotic exosomes is taught in, e.g., Claim 5.
Response to Argument – NSDP, 11,123,376
Applicant’s argument of 1/7/26 has been considered but is not found persuasive.
Applicant argues that they will file a terminal disclaimer, to overcome the rejections (p. 6, paragraph 5).
Such is not persuasive. As Applicant has not filed the Terminal Disclaimer yet, the rejection 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 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 amendments, removing the forms of administration, the rejections of Claims 1, 21, 25, 31, and 33 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, are withdrawn.
It should be noted that, as taught in paragraph 97: the Artisan understands the route of administration relative to target tissue(s). Thus, there is no further rejection for further administration routes.
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 25 and 27-29 remain 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 the cuprizone-model of MS in mice, does not reasonably provide enablement for the breadth of species and demyelinating diseases encompassed. 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 encompass a generic method (now actually broader than acting on demyelination which is now canceled from the claims, via the administration, by any method, to a subject exhibiting demyelination of a neuronal cell, an effective amount of the mammalian amniotic exosomes of an allogenic mammal’s amnion epithelial cells (Claim 25). Claim 26 is canceled, but contained a bunch of diseases that exhibit demyelination. It is argued that these are clearly still encompassed in the broad claims. Claim 27 is to treat a human. Claim 28: limits the exosomes to have been derived from a bank of immortal mammal amnion epithelial cell lines. Claim 29 limits the exosomes to having been lyophilized, and derived from immortal mammal amniotic cell lines.
The claims are taught in the specification for treating various demyelinating diseases (e.g., paragraph 72). It is noted that Claim 26, now canceled, claimed the various diseases. However, while canceled from the particular claim, it is also clear the broad claims are drawn to encompass these diseases.
The specification teaches that the exosomes are useful in promoting myelination and thus are useful in treating demyelination diseases, e.g., MS (paragraph 16). The facilitation of remyelination to treat demyelination disorders, including several disorders (e.g., paragraph 72). A further statement of contemplation of treating demyelination diseases is again provided in paragraph 77, where “treatment” is defined as repair, regeneration, or promotion of regeneration and/or reparation of cells, tissues and physiological pathways, including neuronal and endocrine pathways. A general statement of a medicament of the exosomes is made for treatment of demyelinating disease is made (paragraph 90). Beyond the mere antecedent basis, and congruent with these teachings of remyelination, the specification at Example 9 proposes (prophetically) that the exosomes will promote remyelination and be use in MS, optic neuritis, Devic’s disease, etc., but such is not a demonstration of its ability remyelinate demyelinated tissue in these instances. However, all of this description is excluded, as the claims now are to reducing or inhibiting demyelination in a mammalian subject.
The description for demyelination reduction/inhibition is limited to Example 17. Example 17 shows an experiment on the cuprizone mouse model of MS, testing the effect of exosomes on a 5 day course of cuprizone. In it, it is found that exosomes provided better weight retention for the mice, as well as reduced demyelination. However, this is limited to the aspect of ameliorating the demyelination process, as remyelination was not allowed to take place. Still further, the Art demonstrates that the cuprizone model of MS is not understood sufficiently and MS is not understood sufficiently to say that the mechanisms of demyelination are the same, and the information of remyelinating the tissues is simply not even present. I.e., inhibiting demyelination is not the same causing re-myelination of demyelinated tissue. To support this, Praet, et al. (2014) “Cellular and molecular neuropathology of the cuprizone mouse model: Clinical relevance for multiple sclerosis”, Neuroscience and Biobehavioral Reviews, 47: 485-505, demonstrates that the cuprizone model is not predictive of therapy, but is simply used as a tool to study MS, schizophrenia and epilepsy. To wit, “it is clear that further research will be necessary to fully understand the mechanism(s) behind CPZ-induced pathology” (p. 501, paragraph 1). Moreover, with regard to other demyelinating diseases, e.g., Claim 26 recites MS, optic neuritis, Devic’s disease, transverse myelitis, acute disseminated encephalomyelitis, adrenoleukodystrophy, and adrenomyeloneuropathy, such is taught in the specification as being limited to remyelination, not reducing/inhibiting demyelination (e.g., paragraph 72 is directed to “repair, regeneration and reparation” of the cells; paragraph 77 states the treatment is to “repair, regeneration or promotion of regeneration and/or reparation”, and example 9 states that it is to promote myelination, not reduce demyelination). Further, while there is no evidence the exosomes will hasten remyelination in the model, or the other disorders encompassed by the claims, it would certainly not correlate to treating other disorders, and other demyelination processes which may differ from that multiple sclerosis. Multiple sclerosis is believed to be due to autoimmune disease and a complex interplay of genetic and environmental factors, while adrenoleukodystrophy is caused by a defect in ABCD1 gene, leading to accumulation of very long chain fatty acids that damage myelin (Weber, et al. (2014) “X-linked adrenoleukodystrophy: very long-chain fatty acid metabolism is severely impaired in monocytes by not in leukocytes”, Human Molecular Genetics, 23(10): 2542-50, e.g., ABSTRACT). Being caused by distinct things, necessarily indicates that the action on one mechanism does not equate to the same action on the other mechanism. Still further some demyelination diseases are not caused by direct chemical insult, but by viruses, which necessarily indicates they are distinct in their mechanisms (Fazakerley and Walker (2003) “Virus demyelination”, Journal of NeuroVirology, 9: 148-64, e.g., ABSTRACT). Finally, even for the cuprizone model in mice, no translational studies have been found to say it correlates to other species of mammal, and thus, it would require testing in other mammals to see if it would work.
Lastly, it should be noted that even Applicant states in the specification, in paragraph 183:
Further analysis of the number and activation state of microglia, astrocytes and oligodendrocytes in the brain will provide more information about the therapeutic potential of hAEC derived EVs.
From this, Applicant themselves admit that the therapeutic potential of these exosomes is yet to be determined.
Thus, the Artisan would have to experiment to determine if the exosomes could reduce/inhibit demyelination in all forms of demyelinating disease, and stop demyelination in all forms of demyelinating disease and mammal, except for cuprizone-induced MS in mice. Such would be considered undue as it is required for the vast majority of embodiments claimed. Thus, the claims are not enabled for more than the cuprizone-induced MS model mouse.
Response to Argument – Enablement
Applicant’s argument of 1/7/26 has been considered but is not found persuasive.
Applicant argues that have canceled Claim 26, and amended Claim 25 to simply recite “a method comprising”. In doing so, Applicant argues that the 112 rejection is enabled fro the recited step. Page 8, paragraphs 5-7).
Such is not persuasive. There must be a patentable reason for such administrations, and the claims also still require administration to the subset of subjects exhibiting demyelination of a neuronal cell. Such is clearly taught in the specification for the patentable purpose of treating disease. See, e.g., paragraph 72 of the specification.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
In light of the cancelation of Claims 34-35, the rejections of Claims 33-35 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.
To wit, by canceling the dependent claims, they no longer indicate an issue with remaining Claim 33.
Claims 33 and 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.
As seen by Claim 33 and 36, each aims to reduce post-stroke infarct damage in a mammal, by administration of allogeneic ASC-EVs. While Claim 33 provides no recognition of what is reduced, as far as post-stroke infarct damage, Claim 36 requires apoptosis and glial scar density to be reduced, by the method. Thus, we can see Claim 33 specifically embraces other aspects of post-stroke infarct damage than those of apoptosis and glial scar density, and can be done without cause reduced apoptosis and glial scar density. Further, Claim 36 implies that apoptosis and glial scar density can be reduced, with no other effect on the infarct damage.
The specification fails to teach anywhere, how to only reduce apoptosis and glial scar density, with no other effects. Nor does it teach how to treat post-stroke infarct damage, without affecting reduced apoptosis and glial scar density. In fact, the examples only teach all these things going on, at the same time. E.g., Examples 14-16. I.e., when it is looked for, the treatment provides for enhanced grip function and reduced infarct damage, but not forepaw asymmetry or adhesive removal ability 7 days post-stroke (paragraph 172). Reduced infiltration of myeloid cells and macrophages, but not microglia or lymphoid cells, 7 days post-stroke (paragraph 173). Reduced apoptosis and glial scar density, 7 days post-stroke (paragraph 174). Similar to the above, a 28 day test shows enhanced grip function and reduced infarct damage, but not forepaw asymmetry or adhesive removal ability (paragraph 176); no further enhancement to regeneration mechanisms, but reduced glial scar density at 28 days (paragraph 177). Again, when looked for, all these effects occur, and there is no way taught to affect any particular one, or subset, without affecting any other.
The Art does not provide more.
Thus, the Artisan would not have understood Applicant to have been in possession of the invention as claimed, at the time of filing.
Allowable Subject Matter
Claims 3-4 and 15 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claim is allowed.
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.
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