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 . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1, 4-5, 10, 13, 15, 17-18, 29, 36, 49, 55, 86-87 and 102, in the reply filed on 12/5/2025, is acknowledged. Applicant's election of cholesterol (species of sterol), a combination of DHPG and DHPC (species of phospholipid) and IDUA (species of therapeutic moiety), in the reply filed on 12/5/2025, is acknowledged. Applicant timely traversed the restriction (election) requirement in the reply filed on 12/5/25.
The traversal is on the ground(s) that the identified groups share a special technical feature, i.e., the synthetic exosome of claim 1, where claims 117 and 119 recite the exosome of claim 1. Applicant further argued that John does not specify that the synthetic exosomes described therein comprise a lipid bilayer that does not contain an alcohol, as presently claimed. Applicant argued that the Examiner did not provide a rationale as to why the ordinarily skilled artisan would have pursued, in view of John, a synthetic exosome comprising a lipid bilayer that does not contain alcohol.
This is not found persuasive because, as a first, claim 117 recites the synthesis of synthetic exosomes, and is not further limited to the exosome components of claim 1. Secondly, John does not teach exosomes that contained a lipid bilayer with alcohol (see the below Obviousness rejection over John). The claims are not considered patentably distinct from John, and the inventions (see the Restriction Requirement) do not share a special technical feature, in view of John et al.
The requirement is still deemed proper and is therefore made FINAL.
Claims 110-117 and 119 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Objections
Claims 13 and 55 are objected to because of the following informalities:
Claim 13, line three, recites the word “cholesterol” twice. It appears that the second “cholesterol” should be amended with the inclusion of the word “derivative”. In the interest of compact prosecution, the Examiner is interpreting claim 13 as reciting both cholesterol and cholesterol derivative, however, appropriate correction is required.
Claim 55, line 16 recites the phrase “said antibody comprise”, which appears as if it should be removed. Otherwise, the limitation is confusing. Appropriate correction is required.
Further regarding claim 55, the last line recites “Keytuda”, which appears to be a typographical error of the word “Keytruda”. The Applicant is not encouraged to correct the typographical error. Instead, the Applicant is encouraged to amend the claim with the generic name of the drug. In the instant case, Keytruda is a registered trademark, which is not allowed in the claims (see the below 35 USC § 112 rejection).
Claim Rejections - 35 USC § 112 –
Indefiniteness, Trademarks, Indefinite Language
and Broad Limitation followed by Narrow Limitation
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.
Claims 1, 4-5, 10, 13, 15, 17-18, 29, 36, 49, 55, 86 and 102 are 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.
Regarding broad to narrow limitations, 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, claims 1, 4, 15, 18, 29, 49, 55, 86-87 and 102 recite broad recitations, and the claims also recite abbreviations in parentheses, 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.
The Examiner notes that although some claims contain common abbreviations of the recited limitations, abbreviations have more than one meaning. For example, although CNS (e.g., narrow limitation), as recited in claim 1, and BBB, as recited in claim 4, are common abbreviations of Central Nervous System (e.g., broad limitation) and Blood Brain Barrier, respectively, the abbreviations are also those of Clinical Nurse Specialist and Better Business Bureau. As another example, claims 86 and 102 recite Ataxia Telangiectasia Mutated and Amyotrophic Lateral Sclerosis, and further recite ATM and ALS; however, the abbreviations also mean Automated Teller Machine and Advanced Life Support. Regarding claim 29, the Examiner notes that the abbreviations can refer to more than one lipid. For example, DHPC can be diheptanoyl-, as recited, or dihexanoyl-, as is also commonly known in the art of phospholipid science.
The Examiner notes that the abbreviations alone are not indefinite, but, when confined within parentheses, the limitations (broad limitation followed by narrower limitation) become indefinite.
The Examiner recommends that the Applicant carefully review the claims and remove all parentheses, at each instance of occurrence.
Regarding trademark/trade names, claims 15, 17 and 55 contain the trademark/trade names Span 80, Tween 20, BRIJ 76, BRIG 78, BRIJ 96, BRIJ 721; and, Keytuda. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade names are used to identify/describe surfactants and anticancer agents; and, accordingly, the identification/descriptions are indefinite.
The Applicant is encouraged to remove all trademark/trade names from claims 15, 17 and 55.
Regarding indefiniteness, claim 18, line 18, is confusing, and appears to recite an incomplete range of the carbon chain. The claim recites “C-24 alkyl steroid”. The Examiner is unsure as to whether or not the Applicant attempts to claim a C24 alkyl steroid, or another range of the carbon chain that ends with 24 carbon atoms. Clarification and/or amendment of the claimed scope is required.
Regarding indefinite language, and further regarding claims 55 and 102, the phrase "for example" renders the claims indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The Applicant is encouraged to remove the indefinite language from the claims, at each instance of occurrence.
Claim Rejections - 35 USC § 103 - Obviousness
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.
Claim(s) 1, 4-5, 10, 13, 15, 17-18, 29, 36, 49, 55, 86 and 102 are rejected under 35 U.S.C. 103 as being unpatentable over John et al (WO 2019/094679 A1), in view of Fahmy et al (US 2015/0064265A1), further in view of KR 2010/0031320A and further in view of Tzianabos et al (US 2011/0052673 A1).
John taught synthetic exosomes (SEs), provided for the delivery of various therapeutic molecules to the central nervous system including, but not limited to the brain. The SEs described therein were effective to transport large molecules across the blood brain barrier (BBB), and effectively deliver the molecule to the central nervous system [0167]. The exosomes comprised liposomes [0065] ranging in size up to about 500 nm [claim 64], and further comprised a lipid bilayer [0212], phospholipids generally [claim 38], cholesterol [0010] and a non-ionic detergent [0011]. John did not teach, as a required entity, a lipid bilayer that contained an alcohol. Further, John taught that the delivery vesicles contained an enzyme, generally, as a therapeutic agent [claim 1; ¶ 0006].
Although John taught phospholipids, generally, John did not teach the instantly elected DHPC and DHPG. John generally taught enzymes, however, John was not specific IDUA, as instantly elected.
Fahmy taught 1,2-diheptanoyl-SN-glycero-3-phosphocholine (e.g., DHPC) as a suitable phospholipid in the manufacture of the lipid bilayer of liposomes [0095-0097]. The molar ratio of a mixture of one or more phospholipids and one or more additional lipids or sterols ranged from about 1:1 to about 6:1 [0102].
Since John generally taught phospholipids, it would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of John, DHPC, as taught by Fahmy. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. In the instant case, it is prima facie obvious to select DHPC for incorporation into a liposome, based on its recognized suitability for its intended use as a bilayer-forming lipid, as taught by Fahmy at [0095-0097].
The combination of John and Fahmy did not teach DHPG, as instantly elected.
Nevertheless, KR 2010/0031320A taught liposomes [title and abstract], comprising, as a liposome forming lipid [page 8, line 4], 1,2-Dihexanoyl- sn -Glycero-3- [Phospho- rac- (1-Glycerol)] (e.g., DHPG) [page 8, 11th line from bottom].
Since John generally taught phospholipids, it would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of John, DHPG, as taught by KR 2010/0031320A. In the instant case, it is prima facie obvious to select DHPG for incorporation into a liposome, based on its recognized suitability for its intended use as a liposome-forming lipid, as taught by KR 2010/0031320A at [page 8, 11th line from bottom].
The combined teachings of John, Fahmy and KR 2010/0031320A did not teach IDUA as a therapeutic moiety, as instantly elected.
However, Tzianabos taught liposomes comprising, as a therapeutic moiety, alpha iduronidase (e.g., IDUA) [claims 17-18].
Since John generally taught enzymes as therapeutic agents, it would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of John, alpha iduronidase, as taught by Tzianabos. In the instant case, it is prima facie obvious to select alpha iduronidase for incorporation into a liposome, based on its recognized suitability for its intended use as a therapeutic enzyme, as taught by Tzianabos at claims 17-18.
John, in view of Fahmy, KR 2010/0031320A and Tzianabos, reads on claims 1, 5, 18, 29 and 55.
Claim 4 is rendered prima facie obvious because John taught that the exosomes have thermodynamic stability, and provide highly localized payload delivery [0224].
Claim 10 is rendered prima facie obvious because John did not teach glutathione-maleimide-PEG2000-distearoyl phosphatidyl ethanolamine, a transferosome or an ethosome.
Claim 13 is rendered prima facie obvious because John taught that the surfactant detergent ranged from about 5%, or from about 10% up to about 25%, or up to about 20%. In certain embodiments the surfactant/detergent was about 15% by weight [0223].
The instant claim 13 recites a surfactant range from about 1 %, 3 %, 5 %, 8-18 %, 15 %, 13 % or 10 %.
John taught that the surfactant detergent ranged from about 5%, or from about 10% up to about 25%, or up to about 20%. In certain embodiments the surfactant/detergent was about 15% by weight. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", a prima facie case of obviousness exists. MPEP 2144.05 A.
Claims 15 and 17 are rendered prima facie obvious because John taught Span 80 at about 10% to about 20%, or about 15% by weight [claims 55-56].
Claim 36 is rendered prima facie obvious because Fahmy taught, as previously discussed, that the molar ratio of a mixture of one or more phospholipids and one or more additional lipids or sterols ranged from about 1:1 to about 6:1 [Fahmy at ¶ 0102]. Additionally, John’s teachings of a surfactant were previously discussed. And, John taught a zeta potential of -12 mV [see Table 3]. Furthermore, Fahmy’s and KR 2010/0031320A’s teachings of DHPC and DHPG were previously described. The motivation to combine John with each of Fahmy and KR 2010/0031320A, was previously discussed.
The instant claim 36 recites a 3:2:1 molar ratio of DHPG:DHPC:CH; and, a zeta potential of about -20 mV or lower. Fahmy taught that the molar ratio of a mixture of one or more phospholipids and one or more additional lipids or sterols ranged from about 1:1 to about 6:1. John taught a zeta potential of -12 mV. A prima facie case of obviousness exists, as discussed above.
Claim 49 is rendered prima facie obvious because John taught the exosomes surface coated with targeting molecules such as transferrin or folic acid [0216].
Claim 55 is rendered prima facie obvious because John taught, as a therapeutic molecule, sAPPa [0167].
Claim 86 is rendered prima facie obvious because John taught an enzyme for enzyme replacement therapy [0046].
Claim 102 is rendered prima facie obvious because John taught miRNA [0047].
Claim 87 is rejected under 35 U.S.C. 103 as being unpatentable over John et al (WO 2019/094679 A1), in view of Park et al (Nature Neuroscience, 22, 2019, 524-528).
The 35 U.S.C. 103 rejection over John was previously described.
Additionally, John was drawn to the inhibition of BACE [see claim 8], in the treatment of Alzheimer’s disease [¶s 0002-0003, 0005, 0019, 0172, 0174].
John, though, did not teach components of a CRISPR/Cas system for the treatment of Alzheimer’s disease, as recited in claim 87.
Park taught that in vivo gene editing in post-mitotic neurons of the adult brain is a useful strategy for treating neurological diseases. Park developed CRISPR–Cas9 nanocomplexes to target Bace1 suppressed amyloid beta (Aβ)-associated pathologies, and cognitive deficits, in mouse models of Alzheimer’s disease. The CRISPR-Cas9 system was effective in the adult mouse brain, with minimal off-target effects [abstract].
Additionally, Park examined the effects of the Cas9-Bace1 nanocomplex in a second Alzheimer’s disease model. Consistent with previous results, Cas9-Bace1 nanocomplex treatment of these mice decreased the number of Bace1+ cells, reduced Aβ42 secretion, and ameliorated cognitive deficits relative to controls [page 528, 1st paragraph]. These results broaden the application of CRISPR–Cas9 systems to neurodegenerative diseases [abstract].
Since John generally taught the inhibition of BACE, in the treatment of Alzheimer’s disease, it would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of John, components of a CRISPR/Cas system for the treatment of Alzheimer’s disease, as taught by Park. The ordinarily skilled artisan would have been motivated, in the treatment of Alzheimer’s disease, to target Bace1 suppressed amyloid beta (Aβ)-associated pathologies and cognitive deficits; and, to decrease the number of Bace1+ cells, while reducing Aβ42 secretion, and ameliorating cognitive deficits, as taught by Park [abstract and page 528 at the 1st paragraph].
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CELESTE A RONEY whose telephone number is (571)272-5192. The examiner can normally be reached Monday-Friday; 8 AM-6 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana S. Kaup can be reached at 571-272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CELESTE A RONEY/Primary Examiner, Art Unit 1612