Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claims 70-89 are under consideration in the instant Office Action.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statements filed 4/9/2024 fail to fully comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because a duplicate citation for non-patent literature in the IDS was provided and the citations have therefore, been lined through.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 70-89 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Pfeifer et al., WO2007/068411 (IDS 4/9/2024) in view of Lott et al, 2005 (4/9/2024, PTO-892).
Pfeifer teaches methods of treating a disease or disorder which is caused by amyloid or amyloid-like proteins. Pfeifer teaches that their methods and compositions elicit a highly specific and highly effective immune response in animals and humans, and are capable of preventing or alleviating amyloidosis, or the symptoms associated with amyloidosis, in diseases associated with amyloid plaque formation. These diseases include Alzheimer's disease (AD) and Downs' syndrome (DS) (see last paragraph of page 8 and top of page 9; see page 19, last paragraph; page 23, last paragraph), which is on point to “subjects with Down’s syndrome” in instant claims 70, 82 and 88. Pfeifer also teaches that diseases or conditions characterized by a loss of cognitive memory capacity include Down's syndrome and Alzheimer’s disease (AD; see page 2, 1st paragraph), as in instant claims 70, 72-75, 79-81 and 88. In Down’s syndrome, all adults over the age of 40 years develop sufficient neuropathology for a diagnosis of AD, which includes brain amyloid plaques (see Abstract of Lott et al., 2005), so all the symptoms associated with Alzheimer’s are also found in Down's syndrome. Pfeifer teaches that the subjects with these disorders have measurable memory disorder (see page 5, 1st paragraph), cognitive (thinking) impairment and abnormal behavioral changes (see page 5, 3rd paragraph), as recited in instant claims 70, 73-74, 79, and 81. Pfeifer teaches that -amyloid deposits are found in the entorhinal cortex (EC) and are involved in the development of mild cognitive impairment (MCI) and AD (see page 5, 2nd paragraph) as required in instant claims 72 and 80.
Pfeifer discloses an effective therapeutic vaccine composition capable of counteracting the physiological manifestations of the disease, such as the formation of plaques associated with aggregation of fibers of the amyloid protein or amyloid-like peptide (see page 8, 3rd paragraph; pages 22-23) as in instant claims 70, 79 and 88. Pfeifer teaches that the antigenic peptide of the vaccine comprises a peptide fragment from the N-terminal part of the Apeptide, consisting of amino acid residues selected from the group consisting of residues 1-15, 1-14, and 1-13, including functionally equivalent fragments thereof attached to, and incorporated or reconstituted in a carrier particle/adjuvant such as a liposome (see page 9, last paragraph; pages 14-15), as required in instant claims 70, 77-79, 85-86 and 88. Pfeifer discloses that the liposome is composed of constituents selected from dimyristoyl phosphatidyl choline (DMPC), dimyristoyl phosphatidyl ethanolamine (DMPEA), dimyristoyl phosphatidyl glycerol (DMPG), cholesterol and monophosphoryl lipid A (MPLA) or any other adjuvant such as, alum, calcium phosphate, interleukin 1, and/or microcapsules of polysaccharides and proteins (see page 44, 2nd paragraph) as required in instant claims 77-78 and 85-86. Pfeifer teaches modifying the antigenic peptide by attaching antigenic moieties which include palmitic acid hydrophobic moiety (see page 15, 1st paragraph, page 16, 1st paragraph) as required in instant claims 70, 76, 79, 83 and 88-89. Pfeifer teaches modifying the antigenic peptide by attaching between 2 and 4 palmitoyl residues (i.e., palmitic acid) coupled to each terminus of the antigenic peptide to facilitate insertion into the liposome (see page 17, 1st paragraph) as required in instant claims 76, 83-84 and 89. Pfeifer teaches administration of their composition through different routes that include intramuscular routes (see page 49, 2nd paragraph) as in instant claims 79 and 88.
And while Pfeifer teaches using the vaccine to prevent or alleviate amyloidosis (see abstract), such as in a subject having Down’s syndrome, Pfeifer fails to explicitly teach administration of treatment before the development of amyloid plaques and administering to a Down’s syndrome subject below the age of 40 as required in the instant claims 70-71 and 82.
Lott teaches that in Down’s syndrome (DS) all adults over the age of 40 years develop sufficient neuropathology for a diagnosis of AD (see Abstract). Lott teaches that the hallmarks of AD observed in brain tissue from individuals with DS include -amyloid plaques and neurofibrillary tangles; the pathology begins to accumulate in childhood (as young as 8 years) and appears to rise progressively with increasing age. Lott teaches that between the ages of 35 and 45 years, the rate of AD pathology accumulation appears to accelerate (see page 383, 1st column). Lott teaches that A pathology in the DS brain has been well-characterized, typically, in younger individuals (under 30 years, see page 384, 2nd column, “4. A pathogenesis in DS”). Lott teaches that earlier, more soluble forms of A are important in the development of dementia and that there has been a shift to study earlier and more toxic species of A that accumulate prior to extracellular A deposition. Lott teaches that A oligomers are critically important in causing neuronal dysfunction prior to overt neuron loss because oligomers. In particular, A oligomers have been found to impair in vitro cellular processes associated with memory, and therefore oligomers have been associated with memory impairment observed early in the course of the pathogenesis (see page 385, top of 1st column). Lott teaches that there is an age-associated decline in adaptive functioning in DS that may be associated with risk factors common to Alzheimer’s disease (see page 387, 1st column, “8. Clinical correlation"). Lott does not teach administering an antigenic peptide derived from amyloid protein.
It would have been prima facie obvious to the person of ordinary skill in the art to have arrived at the claimed invention from the disclosures of Pfeifer and Lott. The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because of Lott’s teachings that AD symptoms develop early in DS subjects as young as 8 years (see page 383, 1st column) as in instant claims 70-71 and 82. Based on the teachings of Lott, the skilled artisan would have recognized that the early pathology of amyloid disease may be due to the deleterious actions of A oligomers causing neuronal dysfunction prior to overt neuronal loss, and that these early mediators of amyloid pathology are correlated with impairments in memory and cognition. Thus, the presence of A oligomers is associated with memory impairment observed early in the course of the disease pathogenesis (see page 385, top of 1st column).
One of ordinary skill would therefore have been motivated to have administered the vaccine/antigenic peptide of Pfeifer prior to the development of overt brain amyloid plaques in order to reduce or remove the soluble forms of A that are known to be toxic to neurons (i.e., A oligomers). See, for example, page 385, 1st column, 1st paragraph of Lott and Pfeifer's teaching that preventing plaques is possible (paragraph spanning pages 22-23). The skilled artisan would have been motivated to treat the at risk population DS, before these patients develop the predictable cognitive deficits which are associated with A plaques and amyloid neuropathology in the brain. Therefore, the references already teach and motivate the selection of the DS patient population without A associated plaques (i.e., a patient without progressed amyloid neuropathology). One of ordinary skill in the art would have been motivated to provide the earliest possible intervention by administering the treatment even before the occurrence of plaque aggregations associated with Alzheimer's disease pathology, particularly in a Down's syndrome population, since this population is well-known to develop the inevitable disease hallmarks of amyloid aggregates and AD-like pathology. Given that the vaccine of Pfeifer (and of the instant claims) is already taught as being useful for the treatment of a subject having Down’s syndrome, the person of ordinary skill in the art would have had a reasonable expectation that the vaccine could be used successfully in younger Down’s syndrome patients based on the cumulative disclosures of these prior art references.
Therefore, claims 70-89 are obvious over Pfeifer in view of Lott.
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 70-89 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 8,603,487 in view of Pfeifer et al., WO2007/068411 (IDS 4/9/2024). The ‘487 patent claims the same method of treatment within the same patient population, Down's syndrome. The patented ‘487 claims recite treating an amyloid associated disease, such as Downs’s syndrome, by administering an immunogenic amyloid antigenic peptide composition to induce the production of antibodies effective to treat memory/cognitive impairments. However, the ‘487 claims do not specifically teach treating before the formation of plaques.
Pfeifer teaches that antibodies according to their invention can inhibit aggregation of monomeric amyloidogenic amyloid-beta, which can lead to the prevention of formation of amyloid plaques known to cause Alzheimer's disease (see bottom of page 22 and top of 23). Pfeifer clearly provides an expectation of success in preventing monomeric amyloidogenic amyloid-beta peptides from aggregating and forming plaques. Therefore, one of ordinary skill in the art would have been motivated to provide the earliest possible intervention to a patient by administering the treatment even before there are plaque aggregations in the brain, especially in a Down's syndrome population since this population has such an excess expression and production of the amyloidogenic peptide, A, and is known to develop brain amyloid plaques. Therefore, claims 70-89 are obvious over U.S. Patent No. 8,603,487 in view of Pfeifer.
Claims 70-89 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-45 of U.S. Patent No. 7,807,175 in view of Pfeifer et al., WO2007/068411 (IDS 5/20/2014). The ‘175 patent claims are directed to an antigenic construct with an intended use to treat Down’s syndrome and increase the retention of cognitive memory capacity. While the instant claims are directed to a method of treatment and the '175 claims are drawn to a product, they encompass the same intended field of use and patient population. However, the ‘175 patent does not teach treating before the formation of plaques in a subject.
Pfeifer teaches that antibodies according to their invention lead to an inhibition of aggregation of monomeric amyloid beta and leads to prevention of formation of amyloid plaques which are known to cause Alzheimer's disease (see bottom of page 22 and top of 23). Pfeifer clearly provides an expectation of success in preventing monomeric amyloid beta peptides from aggregating. Therefore, one of ordinary skill in the art would have been motivated to have provided the earliest possible intervention by administering the treatment even before there are plaque aggregates present in a patient having Down's syndrome, since this population of patients is known to inevitably develop AD-pathology. Therefore, claims 70-89 are obvious over U.S. Patent No. 7,807,175 in view of Pfeifer.
Conclusion
No claims are allowed.
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/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
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