DETAILED ACTION
Examiner acknowledges receipt of applicant’s reply filed 11/26/2025, in response to the restriction requirement mailed 10/07/2025.
Claims 1 and 3-7 are pending. Claims 6 and 7 are newly added. Claims 1, 3, and 4 are withdrawn for the reasons set forth below.
Claims 5-7 are being examined on the merits in this office 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 .
Election/Restrictions
Applicant’s election of group 2 (claims 5-7) without traverse in the reply filed on 11/26/2026 is acknowledged.
Claims 1, 3, and 4 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/26/2026.
Priority
The filing receipt date 6/20/2024 has the following priority information:
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Drawings
The drawings are objected to for the following reasons.
Figures 1 and 2 are missing a unit of measurement of lactoferrin for the X-axis.
Figures 3-5 contain multiple parts that should be separately identified in the respective figure and figure legend, e.g., Fig 3A, 3B, etc.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Drawings
The drawings are objected to because the figure legends for Figs 7 and 8 appear to be reversed.
Figure 8 correlates with the transgenic mice cognitive function and learning ability tests of example 7. However, the figure legend incorrectly identifies figure 7 is correlating with the cognitive function assay. Example 7 also misidentifies the figure.
Figure 7 appears to correlate with the figure legend of Fig 8. Example 8 also misidentifies the figure.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Sequence Compliance
This application is objected to because the peptide sequences on page 6 are not associated with a sequence identifier (a SEQ ID NO). All sequences longer than ten nucleotides or four amino acids referenced in the specification must include a SEQ ID NO and must be included in the Sequence Listing. See MPEP § 2421-2422. Applicant must amend the specification in response to this office action and must confirm that all peptide sequences of the specification are included in the sequence listing.
Examiner requests that the Applicants review the specification to confirm that all of the sequences, as required, comply with MPEP § 2421-2422.
Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
Claim Objections
Claims 5 and 7 are objected to because of the following informalities:
Claim 5 should be amended to recite “Alzheimer's (Lf)”. Claim 5 should further be amended to recite an effective amount of lactoferrin.
Claim 7 should be amended to depend from claim 6, instead of claim 5. Claim 6 further narrows the limitation of claim 6 by reciting “20-80 µM Lf/g”.
Appropriate correction is required.
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.
Claims 5-7 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.
Claim 5 recites the limitation "the drug composition". There is insufficient antecedent basis for this limitation in the claim.
Because claims 6 and 7 depend from indefinite claim 5 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112, second paragraph.
The metes and bounds of claims 6 and 7 are deemed to be indefinite. Independent claim 5 recites the drug composition comprising lactoferrin and one or more pharmaceutically acceptable excipient. Dependent claim 6 recites wherein the concentration of lactoferrin in the drug composition is 2.5-120 µM Lf/g. Dependent claim 7 recites 20-80 µM Lf/g. Molar concentration relates to the number of moles of solute per liter of solution [liquid]. The measurement µM (micromolar) is one-millionth of a mole per liter. It is unclear what applicant intends by the measurement µM Lf/g. Examiner understands that “Lf” relates to a common acronym for lactoferrin.
The measurement “/g” is unclear in the instant claim scope. Gram relates to a measurement of mass. Independent claim 5 recites the drug composition, thus the “/g” could relate to a unit of measurement relating to overall gram weight of the drug composition (including lactoferrin, and other components such as the claimed “one or more pharmaceutically acceptable excipient”). However, this remains unclear and is not supported by the specification.
Examiner notes that examples 1 and 2 refer to µM concentrations of lactoferrin. Example 3 discloses 40 µg/ml of lactoferrin. The examples do not disclose any measurements of “µM Lf/g”. Claim clarification is required.
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 5-7 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 Alzheimer’s, does not reasonably provide enablement for prophylaxis [reads on preventing] Alzheimer’s. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed in Liebel-Flarsheim Co. v. Medrad, Inc. 481 F.3d 1371, 82 USPQ2d 1113; Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008).
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims; (2) The nature of the invention and the level of predictability in the art; (3) The state of the prior art; (4) The level of one of ordinary skill; (5) The amount of direction provided by the inventor; (6) The existence of working examples; and (7) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
The analysis is as follows:
Breadth of claims. Claim 1 is directed to a method for prophylaxis and treatment of Alzheimer’s disease, comprising administering the drug composition comprising lactoferrin and one or more pharmaceutically acceptable excipient according to claim 1 to a subject in need thereof.
Examiner notes that claim 1 is not limited to any particular amount of lactoferrin. Thus, any and all amounts of lactoferrin would be construed as being useful for a method of prophylaxis and treatment of Alzheimer’s disease.
(2) The nature of the invention and predictability in the art: The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
It is noted that pharmaceutical and biological art is generally unpredictable, requiring each embodiment to be individually assessed for physiological activity. Given this fact, historically the development of new drugs has been difficult and time-consuming. Adding to the unpredictability is that many treatment options may show promise in animal models, but may fail to show therapeutic improvement in clinical trials. There is no absolute predictability, even in view of the high level of skill in the art.
(3) The state of the prior art: The following is a selection of the recited diseases for purposes of illustrating the variety of treatment and disorders. This is not intended to be a comprehensive listing.
Alzheimer’s disease causes progressive cognitive deterioration is characterized by beta amyloid deposits and neurofibrillary tangles in the cerebral cortex and subcortical gray matter (Alzheimer’s disease, Merck Manual, accessed 11/2/2023 at URL merckmanuals.com/professional/neurologic-disorders/delirium-and-dementia/alzheimer-disease, pp. 1-9). Alzheimer’s disease is the most common cause of dementia (p. 2). Most cases of Alzheimer disease are sporadic, with late onset (≥ 65 years) and unclear etiology. Risk of developing the disease is best predicted by age. However, about 5 to 15% of cases are familial; half of these cases have an early (presenile) onset (< 65 years) and are typically related to specific genetic mutations. At least 5 distinct genetic loci, located on chromosomes 1, 12, 14, 19, and 21, influence initiation and progression of Alzheimer disease. Mutations in genes for the amyloid precursor protein, presenilin I, and presenilin II may lead to autosomal dominant forms of Alzheimer disease, typically with early onset. In affected patients, the processing of amyloid precursor protein is altered, leading to deposition and fibrillar aggregation of beta-amyloid; beta-amyloid is the main component of neuritic (senile) plaques, which consist of degenerated axonal or dendritic processes, astrocytes, and glial cells around an amyloid core. Beta-amyloid may also alter kinase and phosphatase activities in ways that eventually lead to hyperphosphorylation of tau (a protein that stabilizes microtubules) and formation of neurofibrillary tangles. Other genetic determinants include the apolipoprotein (apo) E (epsilon) alleles. Apo E proteins influence beta-amyloid deposition, cytoskeletal integrity, and efficiency of neuronal repair. Risk of Alzheimer disease is substantially increased in people with two epsilon-4 alleles and may be decreased in those who have the epsilon-2 allele. For people with two epsilon-4 alleles, risk of developing Alzheimer disease by age 75 is about 10 to 30 times that for people without the allele (pp. 2-3). Cholinesterase inhibitors modestly improve cognitive function and memory in some patients. Other treatments include an N-methyl-d-aspartate (NMDA) receptor antagonist and monoclonal antibodies specific for beta-amyloid oligomers (pp. 6-7).
Hao et al (Curr Prot Pept Sci 20: 139-144 (2019)) teach that lactoferrin (lactotransferrin; Lf) is an iron-binding glycoprotein and one of the most important bioactivators in milk and other external secretions. It has numerous biological roles, including the regulation of iron absorption and modulation of immune responses, and has anti-microbial, anti-viral, antioxidant, anti-cancer, and anti-inflammatory activities (abstract). Lf regulates the quantity of iron absorbed in the intestine via its role in iron transport and can also chelate iron, directly or indirectly. Notably, it has been used as an adjuvant therapy for some intestinal diseases. It is now used in nutraceutical supplemented infant formula and other food products. Id. Lf helps to promote the development of the brain and cognition. Bovine Lf has been shown to protect the brain from neuronal loss and reduce inflammation during antenatal and perinatal stress (p. 142).
(4) The relative skill of those in the art:
MPEP 2141.03 states (in part)” A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) (disagreeing with the examiner’s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering). In the instant case, the skill in the art high with respect to physicians and scientists. The level of skill in the art (physicians and scientists) would be high.
(5) The amount of direction or guidance presented and (6) the presence or absence of working examples: That provided is very limited.
Example 1 discloses an in vitro cell assays in which mouse neuroblastoma cells N2a were treated with 2.5, 5, 10, 20, 40, 80 and 160 μM of Lf for 24 hours. Cell growth following lactoferrin exposure was assessed. The specification discloses there was a dose-response relationship between Lf and N2a cells, in which the low concentration of Lf promoted the cell survival rate and the high concentration inhibited the cell survival rate.
Example 2 assessed the effect of lactoferrin on N2a cells cell viability induced by Aβ25-35. Compared with Aβ25-35 treatment group, the survival rate of N2a cells treated with different concentrations of Lf was significantly improved, and presented a dose-response relationship with the concentration of Lf. Lactoferrin treatment reduced the cell death caused by Aβ25-35.
Example 3 discloses that lactoferrin reduced cell apoptosis induced by Aβ25-35.
Example 4 indicates that lactoferrin reduced pro-inflammatory factors (down regulate expression of TNF-α, IL-6, and IL-1β) and upregulated expression of anti-inflammatory factors IL4 and IL13.
Example 5 indicates that treatment with lactoferrin in an in vitro cell assay decreased activation of TLR4/NFκB/IκBα signal pathway, thereby improving the anti-inflammation ability of N2a cells.
Example 6 discloses an in vitro cell assay of N2a cells in which lactoferrin decrease the expression level of phosphorylated Tau protein (Fig 6 Western blot).
Example 7 discloses APP/PS1 transgenic mice (Alzheimer’s disease mouse model) were treated with saline, low dose lactoferrin (2 mg/kg/d), or high dose lactoferrin (6 mg/kg/d). Mice were assessed for cognitive function and learning ability. Lactoferrin improved cognitive dysfunction of mice, as indicated by improved times in navigation test and spatial protests. The high dose lactoferrin group showed greater improvement over mice treated with a low dose lactoferrin (Fig 8).
Example 8 discloses that the phosphorylation level of Tau protein in the low-dose Lf group and the high-dose Lf group decreased (Fig 7).
There are no examples of prophylaxis or preventing of Alzheimer’s disease. There is no guidance as to lactoferrin amount/routes of administration/dosing regimen that would be necessary in order to provide prophylaxis/preventing Alzheimer’s disease.
(7) The quantity of experimentation necessary: Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 clearly states: "Patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. See Brenner v. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966) (stating, in context of the utility requirement, that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.") Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention." Applicant cannot rely on the knowledge of one skilled in the art to supply information on the novel aspects of the claimed invention. Thus, in view of the reasons set forth above, it would take an undue amount of experimentation for one of skill in the art to practice the claimed invention.
Owing the factors listed above, the amount of experimentation needed will be extensive in view of the lack of guidance by the inventor. MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” Because of the scope of the claim language, one of ordinary skill in the art would be burdened with undue “painstaking experimentation study” to practice the instant claims.
Claim Rejections - 35 USC § 102
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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 5 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Abdelhamid et al (J Alzh Dis 74:245–259 (online Jan 2020)).
Abdelhamid et al teach that lactoferrin (LF) has anti-inflammatory and antioxidant functions, which exert neuroprotective effects against Alzheimer’s disease (AD) (abstract). A mouse model of Alzheimer’s disease was fed a diet supplemented with lactoferrin [reads on drug composition comprising lactoferrin and a pharmaceutically acceptable excipient] (p. 247). LF diets attenuated memory impairment in J20 mice and decreased brain Aβ40 and Aβ42 levels through the inhibition of amyloidogenic processing of AβPP, as it decreased β-site amyloid protein precursor cleaving enzyme 1 (BACE1) levels. LF treatment increased both ApoE secretion and ATP-binding cassette A1 (ABCA1) protein levels in the brains of J20 mice and in primary astrocyte cultures. Moreover, LF promoted extracellular degradation of Aβ in primary astrocyte cultures (abstract, pp. 253-256). Abdelhamid et al teach lactoferrin can be used to treat Alzheimer’s disease.
Accordingly, the limitations of instant claim 5 are satisfied.
Claim(s) 5 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Guo et al (Neuropsychopharmacol. 42:2504–2515 (2017)).
Guo et al teach administration of lactoferrin to an Alzheimer’s disease mouse model. Mice at the age of 6 months were randomly divided into one of three treatment groups (eight mice per group): vehicle control, 2 mg/kg human Lf (hLf; Sigma-Aldrich, L4040), and 6mg/kg hLf. hLf dissolved in saline [reads on drug composition comprising lactoferrin and pharmaceutically acceptable excipient] was administered by intranasal delivery once a day for 3 months, and vehicle control mice were given saline (p. 2505). Lactoferrin improved cognitive decline in amyloid precursor protein (APP)/presenilin 1 (PS1) mice (Fig 1). Lactoferrin decreased expression levels of TNFα and IL-6 (Fig 3, p. 2512). Guo et al teach that lactoferrin can be used to treat Alzheimer’s disease (abstract, pp. 2513-2514).
Accordingly, the limitations of instant claim 5 are satisfied.
Examiner expressly notes that the lactoferrin dosages used in Guo et al (2 mg/kg/day and 6mg/kg/day) are the same used in example 7 of the specification.
Claim(s) 5 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kruzel et al (U.S. 2005/0159340- cited in IDS filed 6/12/2023).
Kruzel et al teach a method for treating Alzheimer’s disease comprising administering an effective amount of lactoferrin and a pharmaceutically acceptable carrier (abstract, paras. [0018], [0034]; Examples 2, 9; claims 1, 8, 13-17). Example 2 discloses preparation of chewable tablets comprising 25 mg lactoferrin, dextrose, citric acid [reads on drug composition comprising lactoferrin and one or more pharmaceutically acceptable excipient]. Example 9 discloses administration of the lactoferrin tablets to a person diagnosed with Alzheimer’s disease. The subject showed improvement cognitive performance. Pharmaceutical or nutritional carriers such as, water, saline, starch, maltodextrin, pullulan, silica, talcum, stearic acid, its magnesium or calcium salt, polyethyleneglycol, arabic, xanthan or locust bean gums and fatty emulsions and suspensions that will be readily apparent to the skilled artisan (para. [0042]).
Accordingly, the limitations of instant claim 5 are satisfied.
Pursuant to MPEP 2121(I), when the reference relied on expressly anticipates or makes obvious all the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). Moreover, MPEP 2121(III) states that a prior art reference provides an enabling disclosure and thus anticipates a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; "proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation." Impax Labs. Inc. v. Aventis Pharm. Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006). MPEP 716.07 states that since in a patent it is presumed that a process if used by one skilled in the art will produce the product or result described therein, such presumption is not overcome by a mere showing that it is possible to operate within the disclosure without obtaining the alleged product. In re Weber, 405 F.2d 1403, 160 USPQ 549 (CCPA 1969).
Claim Rejections - 35 USC § 103
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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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.
Claim(s) 5-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kruzel et al (U.S. 2005/0159340- cited in IDS filed 6/12/2023).
Kruzel et al teach a method for treating Alzheimer’s disease comprising administering an effective amount of lactoferrin and a pharmaceutically acceptable carrier (abstract, paras. [0018], [0034]; Examples 2, 9; claims 1, 8, 13-17). Example 2 discloses preparation of chewable tablets comprising 25 mg lactoferrin, dextrose, citric acid [reads on drug composition comprising lactoferrin and one or more pharmaceutically acceptable excipient]. Example 9 discloses twice daily administration of the lactoferrin tablets to a person diagnosed with Alzheimer’s disease. Each tablet comprised 25 mg, thus 50 mg lactoferrin/day (Exs 2 and 9). The subject showed improvement cognitive performance. Lactoferrin is administered in accordance with the present invention either enteraly, preferably orally, in the form of a powder, aqueous or non-aqueous solution or gel, or parenterally, preferably intravenously, in the form of an injectable solution, as an aid to treat the symptoms of the above-identified disorders. Preferable formulations or medicaments of the present invention comprise lactoferrin alone or in combination with pharmaceutical or nutritional carriers such as, water, saline, starch, maltodextrin, pullulan, silica, talcum, stearic acid, its magnesium or calcium salt, polyethyleneglycol, arabic, xanthan or locoust bean gums and fatty emulsions and suspensions that will be readily apparent to the skilled artisan (para. [0042]).
Kruzel et al do not explicitly teach the lactoferrin concentrations recited in claims 6 and 7. The lactoferrin concentrations are considered result effective variables
It would be obvious to one of ordinary skill in the art to optimize result effective variables such as lactoferrin concentration. MPEP §2144.05 states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). Therefore, it would have been obvious to optimize the concentration of lactoferrin a drug composition to achieve optimal activity and therapeutic effectiveness of the lactoferrin in Alzheimer’s patients.
For example, Kruzel et al taught that the lactoferrin is preferably present in the formulation at a level of 0.1 milligram to 500 milligram, more preferably between 1 to 100 milligram, based on 1 milliliter or 1 gram of the carrier, more preferably between 1 to 100 milligram [reads on 0.1 mg/ml to 500 mg/ml, and 1 mg/ml to 100 mg/ml]. Preferable in treating individual, a single or twice daily dose of 0.01 milligram to 20 milligrams, more preferable 0.1 milligram to 2 milligram of lactoferrin per kilogram of body weight is administrated. Id. Kruzel et al disclose that the molecular weight of lactoferrin is 80 kDa (para. [0042], Fig 3). Thus, Kruzel taught compositions comprising the following lactoferrin micromolar concentrations:
0.1 mg/ml of 80 kDa lactoferrin 1.25 µM
1 mg/ml of 80 kDa lactoferrin 12.5 µM
100 mg/ml of 80 kDa lactoferrin 1250 µM
500 mg/ml of 80 kDa lactoferrin 6250 µM
Kruzel et al further taught an effective amount of lactoferrin varies depending on the individual treated, severity of the neurodegenerative disorder and the form of administration (para [0042]). There is a motivation to optimize since it is normal desire of scientists or artisans to improve upon what is already generally known with a reasonable expectation that optimization would at least work the same.
Accordingly, claims 6 and 7 are rendered obvious in view of the teachings of Kruzel et al.
Pursuant to MPEP 2121(I), when the reference relied on expressly anticipates or makes obvious all the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). Moreover, MPEP 2121(III) states that a prior art reference provides an enabling disclosure and thus anticipates a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; "proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation." Impax Labs. Inc. v. Aventis Pharm. Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006). MPEP 716.07 states that since in a patent it is presumed that a process if used by one skilled in the art will produce the product or result described therein, such presumption is not overcome by a mere showing that it is possible to operate within the disclosure without obtaining the alleged product. In re Weber, 405 F.2d 1403, 160 USPQ 549 (CCPA 1969).
Relevant Art Not Relied Upon
Kruzel et al (U.S. 20030096736- cited in IDS filed 6/12/2023) teach a method for treating Alzheimer’s disease comprising administering an effective amount of lactoferrin and a pharmaceutically acceptable carrier (abstract, paras. [0021], [0028], [0038]; Examples 2, 7; claims 8, 9, 13-16). Example 2 discloses preparation of lactoferrin chewable tablets. Example 7 discloses administration of the lactoferrin tablets to a person diagnosed with Alzheimer’s disease. The subject showed improvement cognitive performance. Kruzel et al. disclose effective amounts of lactoferrin and that the amount of lactoferrin varies depending on the individual treated, severity of the neurodegenerative disorder, and the form of administration (para. [0038]).
Wang et al (EP 2251032) teach administering compositions comprising lactoferrin and a pharmaceutically acceptable excipient to treat Alzheimer’s disease (e.g., paras. [0071]-[0075], claims 11-13). The compositions comprise a therapeutically effective dose of lactoferrin (e.g., paras. [0019]-[0026], claims 1-3, 8,10). Amounts effective for treating the disorder will depend on a number of factors known to those of skill in the art such as the severity of the disorder and the weight and general state of the patient (e.g., para [0019]). The compositions can be combined with other compounds, e.g. sialic acid and/or iron, vitamins, minerals, carbohydrate source (lactose, saccharides, starch) [reads on one or more pharmaceutically acceptable excipient] (e.g., paras. [0027]-[0041], [0048]-[0054]). Figure 1 discloses lactoferrin concentrations of 1 mg/ml, 10 mg/ml, and 100 mg/ml.
As indicated by Kruzel (U.S. 2005/0159340) at para [0044], Fig 3, lactoferrin has a molecular weight of 80 kDa. Thus, Wang et al disclose lactoferrin compositions comprising the following concentrations:
1 mg/ml of 80 kDa lactoferrin 12.5 µM
10 mg/ml of 80 kDa lactoferrin 125 µM
100 mg/ml of 80 kDa lactoferrin 1250 µM
Conclusion
No claims are allowed.
Claims 1 and 3-7 are pending. Claims 1, 3, and 4 are withdrawn.
Claims 5-7 are rejected.
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/KRISTINA M HELLMAN/Examiner, Art Unit 1654