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 .
Withdrawal of Rejections
The response and amendments filed on 03/19/2026 are acknowledged. Any previously applied minor objections and/or minor rejections (i.e., formal matters), not explicitly restated here for brevity, have been withdrawn necessitated by Applicant’s formality correction and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining, if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner’s Response to Arguments section.
Briefly, the previous claim rejections under 35 U.S.C. 112(b) for indefiniteness for all claim rejections, except for the last rejection pertaining to the antibody dilutions, have been withdrawn necessitated by Applicant’s amendments; however, new grounds of rejection have been set forth below. Additionally, the previous claim rejections under 35 U.S.C. 103 for obviousness have been withdrawn necessitated by Applicant’s amendments; however, new grounds of rejection have been set forth below.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Objections
Claims 105 and 141 are objected to because of the following informalities: claim 105 recites “monoclonal or polyclonal antibodies HLA-DRB1 and β2-MG”; however, this should read “monoclonal or polyclonal antibodies to HLA-DRB1 and β2-MG”. Appropriate correction is required. This is an objection, not a rejection, because this appears to be a typographical error.
Claim 115 is objected to because of the following informalities: claim 115 recites “wherein the medicament is produced as solid dosage form”; however, this should read “wherein the medicament is produced as a solid dosage form”. Appropriate correction is required. This is an objection, not a rejection, because this appears to be a typographical error.
Claim 130 is objected to because of the following informalities: claim 130 recites “monoclonal or polyclonal antibodies HLA-DRB1, β2-MG, IFN-γ, CD4”; however, this should read “monoclonal or polyclonal antibodies to HLA-DRB1, β2-MG, IFN-γ, and CD4”. Appropriate correction is required. This is an objection, not a rejection, because this appears to be a typographical error.
Maintained Rejection and/or New Grounds of Rejection Necessitated by Amendments
Claim Rejections - 35 USC § 112(b), Indefiniteness
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 105-109, 111, 115, 130, 134-136, and 140-141 are rejected under 35 U.S.C. 112(b) 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.
Claims 105, 130, and 141 recite the antibody dilutions 10012, 10030, 10050, 100150, and/or 100200; however, it is unclear if all of these dilutions are performed at one time, simultaneously, or if these are individual dilutions for the antibodies. It appears applicant is attempting to claim the process of making the medicament, i.e., product by process limitations. However, the limitation is indefinite since it is unclear what the actual structure of the product is, i.e., it is unclear what the dilution is since the starting concentration of the antibodies is not known. Moreover, regardless of whether the dilutions are performed at one time, simultaneously, or if these are individual dilutions, it is unclear what the concentration of the antibodies in the dilution are since applicant has not provided a starting concentration of the antibodies. For instance, it is unclear if the largest dilutions (i.e., 100150 and 100200), actually contains antibodies because these dilutions are very large and would result in very small, or negligible amounts of antibodies within the composition. Thus, one would not know if they are infringing on the metes and bounds of the claim because it is unclear how many antibodies are contained with the final medicament product. Moreover, in regards to the dilutions of antibodies, the Examiner has interpreted these as product-by-process limitations; therefore, determination of patentability is based on the product itself, not the method of production (see, e.g., MPEP 2113). These product-by-process limitations do not impart structural characteristic(s) to the end product, namely “the medicament”.
Claim 115 recites “neutral carrier granules impregnated lactose with the medicament”; however, it is unclear if the neutral carrier granules are impregnated with lactose, or if the lactose is impregnated with neutral carrier granules. For the purposes of applying prior art, the Examiner has interpreted this to be that the neutral carrier granules are impregnated with lactose.
Claim 140 recites “neutral carrier granules, lactose, impregnated with the medicament”; however, it is unclear from this wording if the neutral carrier granules are lactose and that the lactose is impregnated with the medicament, or if the neutral carrier granules and lactose are impregnated with the medicament. For the purposes of applying prior art, the Examiner has interpreted this to be that the neutral carrier granules are lactose and that the lactose is impregnated with the medicament.
Claims 106-109, 111, and 134-135 are included in this rejection for depending on independent claims 105 or 130 and failing to rectify the noted deficiencies.
Examiner’s Response to Arguments
Applicant's arguments filed 03/19/2026 have been fully considered but they are not persuasive.
Regarding Applicant’s arguments pertaining to the mechanism of action of the drug following the technologically processed dilutions (remarks, page 10), this argument is not persuasive for multiple reasons:
First, the mechanism of action of the antibodies is not relevant to the claimed invention, or to the rejection at hand. The fact that the antibodies exert a “special” mechanism of action following dilutions of the antibodies does not make the invention patentable (see, e.g., MPEP 2112(I)).
Secondly, Applicant has not provided any evidence that the largest dilutions (i.e., 100150 and 100200) actually contains antibodies. The boundaries of the claimed subject matter cannot be ascertained because Applicant has not provided evidence that the medicament(s) comprising the largest dilutions of antibodies isn’t merely just a composition comprising the excipient and the neutral carrier, with no antibodies present. Therefore, these claims do not apprise one of ordinary skill in the art of its scope (see, e.g., MPEP 2173.02(I)); therefore, one would not know if they are infringing on the metes and bounds of the claim because it is unclear how many antibodies are contained with the final medicament product.
Thirdly, a 100200 dilution is equivalent to 200 consecutive 1:100 serial dilutions, which would likely contain negligible to no antibodies. Again, Applicant has not provided evidence to the contrary and arguments provided by the Applicant cannot take the place of evidence (see, e.g., MPEP 716.01(c)(II)). Therefore, it still remains unclear if these medicament(s) with the highest dilutions actually contain antibodies.
Maintained Rejections
Claim Rejections - 35 USC § 101, Ineligible Subject Matter
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 105-109, 111, 115, 130, 134-136, and 140-141 are rejected under 35 U.S.C. 101 because they are drawn to ineligible subject matter (based on the 2019 Revised Patent Subject Matter Eligibility Guidance).
Broadest reasonable interpretation (BRI) of independent claim 105: the broadest scope of claim 105 is drawn to a composition comprising antibodies towards HLA-DRB1 and β2-MG, a excipient, and a neutral carrier.
Broadest reasonable interpretation (BRI) of independent claim 130: the broadest scope of claim 130 is drawn to a composition comprising antibodies towards HLA-DRB1, β2-MG, IFN-γ, and CD4, as well as an excipient.
Broadest reasonable interpretation (BRI) of independent claim 141: the broadest scope of claim 141 is drawn to a composition comprising HLA-DRB1 and β2-MG, a excipient, a neutral carrier, and an antibiotic.
STEP 1: Is the claim directed to a process, machine, manufacture, or a composition of matter?
YES, the claims are directed to a composition of matter.
STEP 2A: PRONG ONE: Does the claim recite an abstract idea, law of nature, or a natural phenomenon?
YES, the claims are considered to be “product of nature” exceptions (i.e., a mixture of naturally occurring products). The courts have held that “products of nature” fall under the law of nature and/or natural phenomena exceptions.
PRONG TWO: Does the claim recite additional elements that integrate the judicial exception into a practical application?
NO, the additional elements or combination of elements in the claims does not impose a meaningful limit on the judicial exception. Note that the markedly different characteristics analysis is used to determine if a nature-based product is a “product of nature” exception. Thus, the markedly different characteristic analysis is part of step 2A, i.e., it helps answer the question of whether a claim is directed to an exception, which is further explained below.
STEP 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
NO, the claimed invention is directed to a law of nature and/or natural phenomena (i.e., product of nature) without significantly more. Note that the claims must be interpreted under the broadest reasonable interpretation (BRI) standard when evaluating for a marked difference. Under BRI, the claims broadly read on antibodies, an excipient, a neutral carrier, and/or an antibiotic.
Antibodies are naturally occurring within the immune system (see, e.g., Holodick et al., “Defining Natural Antibodies”, 2017 – previously cited). Moreover, the instant Specification states the use of “natural antibodies”, which are defined as antibodies present in the circulation of healthy humans (see, e.g., instant Specification, pg. 11). Moreover, dilutions and/or concentrations of a naturally occurring product does not change the product itself and, therefore, is still naturally occurring. The excipient, which can be glycerol, is a naturally occurring 3-carbon alcohol found in the human body (see, e.g., Robergs et al., “Glycerol. Biochemistry, pharmacokinetics and clinical and practical applications; 1998 – newly cited). The neutral carrier can be, for example, water, which is naturally occurring. The antibiotic, which can be tetracycline, is naturally occurring because various identified tetracyclines can be derived from S. aureofaciens, S. rimosus, and S. viridofaciens (see, e.g., Chopra et al., “Tetracycline antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance”; 2001 – newly cited).
Moreover, Applicant has not provided evidence that the largest dilutions performed, such as the 100150 and 100200 dilutions, actually contain antibodies within the compositions that contain these large dilutions. Note the 112b rejection. If these compositions with these large dilutions do not contain antibodies, then the composition would merely contain just water, glycerol, and/or antibiotics, which are all naturally occurring, as discussed above.
There is no indication that the claimed composition has any markedly different characteristic (e.g., structure, function, phenotype, etc.) that is different than what is found in nature. Applicant does not provide evidence showing that the antibodies, excipient (e.g., glycerol), neutral carrier (e.g., water), and antibiotics interact to produce a markedly different structure or characteristic than what is found in nature. Therefore, it appears that the Applicant is merely claiming a naturally occurring product. Moreover, note that MPEP 2106.04(b) also states: “Thus, a synthetic, artificial, or non-naturally occurring product such as a cloned organism or a human-made hybrid plant is not automatically eligible because it was created by human ingenuity or intervention. Instead, the key to the eligibility of all non-naturally occurring products is whether they possess a markedly different characteristic from any naturally occurring counterpart.”
Therefore, the claims are interpreted under the BRI standard, wherein the claims do not include additional elements that are sufficient to amount of significant more than the judicial exception because the claims do not recite any additional elements.
Therefore, the claims as a whole are considered products of nature which are directed to judicially recognized exceptions without amounting to significantly more from what occurs in nature and thus, are not eligible under 35 U.S.C. 101.
Examiner’s Response to Arguments
Applicant's arguments filed 03/19/2026 have been fully considered but they are not persuasive.
Regarding Applicant’s arguments pertaining to the Applicant’s pervious work and use of the terms “activated form of antibodies”, “activated potentiated form of antibodies”, “ultrahigh dilutions” and “ultralow doses of antibodies” (remarks, page 11), this argument is not persuasive because Applicant is merely claiming and arguing about antibodies that have been diluted. Just because Applicant is diluting the antibodies does not change the product itself. The composition still contains naturally occurring antibodies to HLA-DRB1, β2-MG, CD4, and/or IFN-γ. All the dilution(s) do is cause the concentration of the antibodies to decrease from the stock solution concentration. Moreover, the dilutions does not change the product itself, and therefore, is still naturally occurring.
Regarding Applicant’s arguments pertaining to the antibodies acquiring a “special” property following the dilutions (remarks, pages 10-11), this argument is not persuasive because, as discussed above, the mechanism of action of the antibodies is not relevant to the claimed invention, or to the rejection at hand. The fact that the antibodies exert a “special” mechanism of action following dilutions of the antibodies does not make the invention patentable (see, e.g., MPEP 2112(I)). Additionally, as noted above, the BRI of the instantly claimed invention pertains to a composition comprising antibodies towards HLA-DRB1, β2-MG, CD4, and/or IFN-γ, a excipient, and a neutral carrier. The claimed invention does not pertain to the “special” properties that the antibodies exhibit following dilution.
Regarding Applicant’s arguments pertaining to the NMR data for IFN-γ (remarks, page 12), this argument is not persuasive because Applicant is merely showing how the NMR spectra shifts when IFN-γ is added, compared to placebo. For the data presented in the NMR spectra, Applicant has not provided information pertaining to the dilutions(s) of IFN-γ, nor it is apparent from the NMR spectra how these antibodies have conformational changes. Additionally, the data presented in Figure 1 only shows the NMR spectra for IFN-γ, not the HLA-DRB1, β2-MG, and CD4 antibodies. Furthermore, the data presented in Figure 1 of the remarks is blurry and not in color, as the description states. Applicant should submit any supportive data in an affidavit under 37 CFR 1.132.
Regarding Applicant’s argument that the initial substance does not disappear after multiple serial dilutions (remarks, page 12), this argument is not persuasive because Applicant does not provide evidence that the highest dilutions, such as 100150 and 100200, actually contains antibodies. The prior art referenced in the arguments (Epstein O.I., The phenomenon of release activity and the hypothesis of “spatial” homeostasis”) doesn’t even contemplate or show if 100150 and 100200 dilutions of HLA-DRB1, β2-MG, CD4, and/or IFN-γ antibodies even result in antibodies present in the final composition. Additionally, as discussed above, a 100200 dilution is equivalent to 200 consecutive 1:100 serial dilutions, which would likely contain negligible to no antibodies. Again, Applicant has not provided evidence to the contrary and arguments provided by the Applicant cannot take the place of evidence (see, e.g., MPEP 716.01(c)(II)).
Regarding Applicant’s argument pertaining to shaking the antibodies for obtaining ultra-high dilutions (remarks, pages 13-14), this argument is not persuasive because the physical acts of diluting and shaking the antibodies are considered product-by-process limitations, which does not impart structural characteristic(s) to the end product, namely “the medicament”. The composition still pertains to a medicament comprising antibodies, an excipient, and a neutral carrier.
Regarding Applicant’s arguments pertaining to the therapeutic effect of the claimed dilutions (remarks, pages 14-15), this argument is not persuasive because these “therapeutic effects” are intended use limitations. The intended use does not impart a structure limitation for the claimed product (i.e., the medicament). MPEP 2106.04(d)(2) states “If the limitation does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception under the "treatment or prophylaxis" consideration”; therefore, the therapeutic affects imparted by the medicament are considered intended use limitations which do not integrate the judicial exception into practical application. Moreover, the treatment limitation is not particular, in that is encompasses many application of the judicial exception; therefore, the treatment step is not particular and is instead merely instructions to “apply” the exception in a generic way (see, e.g., MPEP 2106.04(d)(2)).
Regarding Applicant’s arguments that the monoclonal and polyclonal antibodies are not produced naturally (remarks, page 16), this argument is not persuasive because, as discussed above, Holodick teaches that antibodies are naturally occurring within the immune system. Moreover, the instant Specification teaches the use of “natural antibodies”, which are defined as antibodies present in the circulation of healthy humans (see, e.g., instant Specification, pg. 11). Therefore, based on the instant Specification, antibodies are naturally occurring. Additionally, as discussed above, dilutions and/or concentrations of a naturally occurring product does not change the product itself and, therefore, is still naturally occurring. For example, if one were to obtain a stock solution of CD4 antibodies, for example, and perform a dilution, the resulting diluted CD4 antibody solution would still be an unchanged composition comprising CD4 antibodies. Nothing has changed except the concentration of the naturally occurring antibodies.
Regarding Applicant’s arguments pertaining to the specific combination of antibodies and the unexpected synergy (remarks, page 18), these arguments are not persuasive because Applicant has not provided evidence that the different combination of antibodies produces a markedly different interaction. Furthermore, as discussed above, Applicant has not provided evidence that the dilutions actually contain antibodies or not.
Applicant’s arguments are not persuasive to overcome the 35 U.S.C. 101 rejection.
New Grounds of Rejection Necessitated by Amendments
Claim Rejections - 35 USC § 103, Obviousness
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 105-109, 111, 115, 130, 134-136, and 140 are rejected under 35 U.S.C. 103 as being unpatentable over Epshtein 2003 (RU 2205025; Date of Publication: May 27, 2003 – previously cited) in view of Epshtein 2014 (RU 2521392; Date of Publication: June 27, 2014 – previously cited).
Applicant is requested to note the 112b rejection above for how claims have been interpreted by the Examiner. Additional, or reiterated, interpretations have been included in the following 103 rejection.
Epshtein 2003’s general disclosure relates to correction of immune responses by “administration of activated forms of super small doses of monoclonal, polyclonal immune or natural antibodies raised to antigen of the main histocompatibility complex or to antigen complex and associated with its peptide obtained by multiple successive dilution and external effect” (see, e.g., Epshtein 2003, English translation, abstract). Moreover, Epshtein 2003 discloses that a medicament comprising HLA-DRB1 and β2-MG antibodies is “characterized by the presence of immunotropic activity, the absence of side effects, environmental cleanliness and low cost” (see, e.g., Epshtein 2003, English Translation, “Description”, pg. 2). Additionally, Epstein 2003 teaches that the medicament comprising HLA-DRB1 and β2-MG antibodies can be used to treat a immunopathological condition and diseases accompanied by a violation of the immune response (see, e.g., Epshtein 2003, English Translation, “Description”, pg. 2), which can encompass infections.
Regarding claims 105 and 130 pertaining to the medicament, Epshtein 2003 teaches a “medicament for correcting the immune response comprises an activated form of ultra-small doses of monoclonal, polyclonal immune or natural antibodies to the major histocompatibility complex antigen, HLA (predominantly Class I or II), or to the complex of the HLA molecule and its associated peptide” (see, e.g., Epshtein 2003, English translation, “Description”, pg. 2). Moreover, “antibodies to the major histocompatibility complex antigen, HLA (predominantly Class I or II), or to the complex of the HLA molecule and its associated peptide” (see, e.g., Epshtein, 2003, English translation, “Description”, pg. 2) can include HLA-DRB1 and β2-MG. Regarding the volume ratio, Epshtein 2003 teaches that the antibodies can be “a mixture of various, mainly hundreds, of homeopathic dilutions” (see, e.g., Epshtein 2003, English translation, pg. 1), which can include a 1:1 volume ratio, or other volume ratios, or other dilutions, of HLA-DRB1 and β2-MG antibodies. Epshtein 2003 teaches that the medicament is prepared “in the form of alcoholic or aqueous solutions” (see, e.g., Epshtein 2003, English translation, “Description”, pg. 2). Moreover, the recitation of the multiple dilutions of the antibodies have been interpreted as product-by-process limitations; therefore, determination of patentability is based on the product itself, not the method of production (see, e.g., MPEP 2113). These product-by-process limitations do not impart structural characteristic(s) to the end product, namely “the medicament”.
Regarding claims 115 and 140 pertaining the solid dosage form, Epshtein 2003 teaches a “medicament for correcting the immune response comprises an activated form of ultra-small doses of monoclonal, polyclonal immune or natural antibodies to the major histocompatibility complex antigen, HLA (predominantly Class I or II), or to the complex of the HLA molecule and its associated peptide; the activated form is obtained by repeated sequential dilution and external action, preferably by homeopathic technology” (see, e.g., Epshtein 2003, English translation, abstract) and that the medicament is prepared in the form of granules (see, e.g., Epshtein 2003, English translation, “Description”, pg. 2).
However, Epshtein 2003 does not teach: an excipient (claims 105 and 130); or a neutral carrier (claims 105 and 130); or wherein the stock substances are at a concentration of 0.5-5.0 mg/mL (claims 105 and 130); or wherein the medicament comprises antibodies to CD4 and IFN-γ (claim 130).
Epshtein 2014’s general disclosure relates to a therapy for the treatment of viral infections, wherein the therapy contains “an activated-potentiated form of human gamma-interferon (IFN-γ) antibodies and an activated potentiated form of CD4 receptor antibodies” (see, e.g., Epshtein 2014, English translation, abstract). Moreover, Epshtein 2014 discloses that this medicament comprising IFN-γ and CD4 antibodies can be used to treat acute and chronic viral diseases, included acute viral hepatitis A, B, C and other viral hepatitis and herpes virus infections (see, e.g., Epshtein 2014, English Translation, “Description”, pg. 2).
Regarding claims 105, 115, 130, and 140 pertaining to the medicament, Epshtein 2014 teaches “the drug can be made in solid dosage form in the form of a pharmaceutical composition and contain the technologically necessary amount of a neutral carrier saturated with a mixture of aqueous or aqueous-alcoholic solutions of the activated-potentiated form of antibodies to human gamma-interferon and the activated-potentiated form of antibodies to the CD4 receptor, and pharmaceutically acceptable additives, which include, for example, lactose, microcrystalline cellulose and magnesium stearate” (see, e.g., Epshtein 2014, English Translation, “Description”, pg. 2). In regards to the stock substances concentration, Epshtein 2014 teaches that the concentration of the matrix solution is “0.5 ÷ 5.0 mg/ml, preferably 2.0 ÷ 3.0 mg/ml” (see, e.g., Epshtein 2014, pg. 6). Additionally, Epshtein 2014 teaches an example wherein 2.5 mg/ml of stock antibodies are used (see, e.g., Epshtein 2014, pg. 6). In regards to the multiple serial dilutions for the CD4 and IFN-γ antibodies, Epshtein 2014 teaches diluting the stock matrix solution 10012, 10030, and 10050 times (see, e.g., Epshtein 2014, pg. 6). Moreover, as discussed above, the recitation of the multiple dilutions of the antibodies are considered product-by-process limitations; therefore, determination of patentability is based on the product itself, not the method of production (see, e.g., MPEP 2113). These product-by-process limitations do not impart structural characteristic(s) to the end product, namely “the medicament”. In regards to the volume ratio of antibodies, Epshtein 2014 teaches a 1:1 ratio of IFN-γ:CD4 antibodies (see, e.g., Epshtein 2014, English translation, pg. 2).
It would have been first obvious to one of ordinary skill in the art to combine Epshtein 2003’s HLA-DRB1 and β2-MG antibody medicament with an excipient and a neutral carrier, as taught by Epshtein 2014. One would have been motivated to do so because Epshtein 2014 teaches that the neutral carrier and excipient are used to create a solid dosage form of the pharmaceutical composition containing the IFN-γ and CD4 antibodies (see, e.g., Epshtein 2014, English Translation, “Description”, pg. 2). Moreover, Epshtein 2003 teaches that the medicament comprising the HLA-DRB1 and β2-MG antibodies can be formulated into a tablet (i.e., solid dosage form) comprising multiple dilutions of the antibodies (see, e.g., Epshtein 2003, English Translation, “Description”, pg. 2). Therefore, based on the teachings of Epshtein 2003 and Epstein 2014, it would have been obvious to combine HLA-DRB1 and β2-MG antibodies with an excipient and a neutral carrier.
It would have been secondly obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Epshtein 2003’s HLA-DRB1 and β2-MG antibodies with Epshtein 2014’s IFN-γ and CD4 antibodies. One would have been motivated to do so because Epshtein 2014 teaches a medicament comprising IFN-γ and CD4 antibodies for the treatment of acute and chronic viral infections (see, e.g., Epshtein 2014, English Translation, “Description”, pgs. 1-2). Additionally, Epshtein 2014 teaches “The proposed combination of activated-potentiated forms of antibodies to human gamma-interferon and to CD4 receptor in a pharmaceutical composition provides an unexpected synergistic therapeutic effect, experimentally confirmed in an adequate model, which consists in increasing the effectiveness of treatment of acute and chronic viral diseases, including herpes, acute viral hepatitis A, B, C and other viral hepatitis, herpes virus infections, due to the immunotropic effect of the components including if increased interferon-dependent activation of CD4 lymphocytes, an increase in the number of receptors on the surface of CD4 cells, IFN-γ receptors, increased expression of gamma-interferon, etc.” (see, e.g., Epshtein 2014, English Translation, “Description”, pg. 2). Moreover, Epshtein 2003 teaches that the medicament comprising HLA-DRB1 and β2-MG antibodies is “characterized by the presence of immunotropic activity, the absence of side effects, environmental cleanliness and low cost” (see, e.g., Epshtein 2003, English Translation, “Description”, pg. 2). Additionally, Epstein 2003 teaches that the medicament comprising HLA-DRB1 and β2-MG antibodies can be used to treat a immunopathological condition and diseases accompanied by a violation of the immune response (see, e.g., Epshtein 2003, English Translation, “Description”, pg. 2), which can encompass infections. Therefore, based on the teachings of Epshtein 2003 and Epstein 2014, it would have been obvious to combine HLA-DRB1, β2-MG, IFN-γ, and CD4 within one medicament. One would have expected success because Epshtein 2003 and Epshtein 204 both teach compositions comprising antibodies.
Regarding claims 105-109, 111, 130, and 134-136 pertaining to the treatment of bacterial and/or viral infections, these have been interpreted as intended use limitations and do not carry patentable weight. The intended use does not impart a structure limitation for the claimed product (i.e., the medicament) and the combined prior art of Epshtein 2003 and Epshtein 2014 teaches the instantly composition; therefore, the structure is capable of performing the intended use.
Regarding the recitation of the volume ratio limitations in claims 105 and 130, those working in the biological and/or pharmaceutical arts would understand that the adjustments of particular conventional working conditions (e.g., concentration or amount of a compound) is deemed a matter of judicious selection and routine optimization, which is within the purview of the skilled artisan. Therefore, one of ordinary skill in the art would want to optimize the amount of antibody used while maintaining the goal of correcting and immune response. For example, the disclosure of Epshtein 2003 teaches “the activated form is obtained by repeated sequential dilution and external action, preferably by homeopathic technology” (see, e.g., Epshtein 2003, English translation, abstract)”; therefore, one of ordinary skill in the art would reasonably conclude that a 1:1 ratio, multiple dilutions of stock antibodies, or other combinations of dilutions of HLA-DRB1:β2-MG antibodies can be obtained. Moreover, Epshtein 2003 teaches serial dilutions for the antibodies while still maintaining the goal of correcting an immune response; therefore, one of ordinary skill in the art would expect success by optimizing the amount or concentration of antibodies while still correcting an immune response. This is motivation for someone of ordinary skill in the art to practice or test the parameter widely to find those that are functional or optimal which then would be inclusive or cover the steps as instantly claimed. Applicant should note the 112(b) rejection for how the Examiner has interpreted these volume ratio limitations because the multiple serial dilutions were interpreted as product-by-process limitations, and it is unclear what the final concentration of the antibodies are in the medicament product. Absent any teaching of criticality by the Applicant concerning concentration, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are result effective variables which can be met as a matter of routine optimization. See MPEP 2144.05
Claim 141 is rejected under 35 U.S.C. 103 as being unpatentable over Epshtein 2003 (RU 2205025; Date of Publication: May 27, 2003 – previously cited) in view of Epshtein 2014 (RU 2521392; Date of Publication: June 27, 2014 – previously cited), Nagy (Anti-bacterial Monoclonal Antibodies; 2018 – previously cited), and LiverTox (Clinical and Research Information on Drug-Induced Liver Injury; 2019 – newly cited).
Epshtein 2003’s general disclosure is discussed above.
Regarding claim 141 pertaining to the medicament, Epshtein 2003 teaches a “medicament for correcting the immune response comprises an activated form of ultra-small doses of monoclonal, polyclonal immune or natural antibodies to the major histocompatibility complex antigen, HLA (predominantly Class I or II), or to the complex of the HLA molecule and its associated peptide” (see, e.g., Epshtein 2003, English translation, “Description”, pg. 2). Moreover, “antibodies to the major histocompatibility complex antigen, HLA (predominantly Class I or II), or to the complex of the HLA molecule and its associated peptide” (see, e.g., Epshtein, 2003, English translation, “Description”, pg. 2) can include HLA-DRB1 and β2-MG. Regarding the volume ratio, Epshtein 2003 teaches that the antibodies can be “a mixture of various, mainly hundreds, of homeopathic dilutions” (see, e.g., Epshtein 2003, English translation, pg. 1), which can include a 1:1 volume ratio, or other volume ratios, of HLA-DRB1 and β2-MG antibodies. Epshtein 2003 teaches that the medicament is prepared “in the form of alcoholic or aqueous solutions” (see, e.g., Epshtein 2003, English translation, “Description”, pg. 2). Moreover, as discussed above, the recitation of the multiple dilutions of the antibodies have been interpreted as product-by-process limitations; therefore, determination of patentability is based on the product itself, not the method of production (see, e.g., MPEP 2113). These product-by-process limitations do not impart structural characteristic(s) to the end product, namely “the medicament”.
However, Epshtein 2003 does not teach: an excipient (claim 141); or a neutral carrier (claim 141); or an antibiotic (claim 141); or wherein the stock substances are at a concentration of 0.5-5.0 mg/mL (claim 141).
Epshtein 2014’s general disclosure is discussed above.
Regarding claim 141 pertaining to the medicament, Epshtein 2014 teaches pharmaceutically acceptable additives, which include, for example, lactose, microcrystalline cellulose and magnesium stearate” (see, e.g., Epshtein 2014, English Translation, “Description”, pg. 2). In regards to the neutral carrier Epshtein 2014 teaches “the drug can be made in solid dosage form in the form of a pharmaceutical composition and contain the technologically necessary amount of a neutral carrier saturated with a mixture of aqueous or aqueous-alcoholic solutions of the activated-potentiated form of antibodies” (see, e.g., Epshtein 2014, English Translation, “Description”, pg. 2). In regards to the stock substances concentration, Epshtein 2014 teaches that the concentration of the matrix solution is “0.5 ÷ 5.0 mg/ml, preferably 2.0 ÷ 3.0 mg/ml” (see, e.g., Epshtein 2014, pg. 6). Additionally, Epshtein 2014 teaches an example wherein 2.5 mg/ml of stock antibodies are used (see, e.g., Epshtein 2014, pg. 6).
Nagy’s general disclosure relates to the use of antibody-based therapeutics for the treatment of bacterial infections due to the failing efficacy of antibiotics (see, e.g., Nagy, abstract). Additionally, Nagy teaches that antibody therapeutics are more efficient than antibiotics alone, as antibodies can target more than one virulence factor and/or combine different modes of action (see, e.g., Nagy, abstract).
Regarding claim 141 pertaining to the combination of antibiotics and antibodies, Nagy teaches that antibodies “act synergistically with antibiotics providing levels of protection significantly greater than see with antibiotics or the antibody alone” (see, e.g., Nagy, Introduction).
LiverTox’s general disclosure relates to the administration of gentamicin to treat bacterial infections. Moreover, LiverTox discloses “Gentamicin is a parenterally administered, broad spectrum aminoglycoside antibiotic typically used for moderate to severe gram negative infections” (see, e.g., LiverTox, Introduction).
Regarding claim 141 pertaining to the specific types of antibiotics, LiverTox teaches “Gentamicin (jen" ta mye' sin) is a aminoglycoside with broad bacteriocidal activity against many aerobic gram negative and some aerobic gram positive organisms. Gentamicin is the most commonly used aminoglycoside antibiotic and is indicated for moderate-to-severe bacterial infections caused by sensitive agents, primarily gram negative bacteria” (see, e.g., LiverTox, Background). Moreover, LiverTox teaches “Gentamicin and other aminoglycosides are typically used in combination with a penicillin or cephalosporin for treatment of severe infections with E. coli, Staphylococcus aureus, Enterobacter, Klebsiella, Serratia, Pseudomonas aeruginosa, and other gram negative bacteria resistant to less toxic antibiotics. Gentamicin is most commonly used for septicemia, bacterial endocarditis, peritonitis, meningitis, pelvic inflammatory disease and pneumonia” (see, e.g., LiverTox, Background).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Epshtein 2003’s HLA-DRB1 and β2-MG antibody medicament with antibiotics, such as gentamicin, as taught by Nagy and Livertox. One would have been motivated to do so because LiverTox teaches that gentamicin is commonly used to treat infections caused by gram negative bacteria, and are used in combination with other antibiotics to treat “E. coli, Staphylococcus aureus, Enterobacter, Klebsiella, Serratia, Pseudomonas aeruginosa, and other gram negative bacteria resistant to less toxic antibiotics” (see, e.g., LiverTox, Background). Nagy teaches that antibody therapeutics are more efficient than antibiotics alone, as antibodies can target more than one virulence factor and/or combine different modes of action (see, e.g., Nagy, abstract). Additionally, Nagy teaches that antibodies “act synergistically with antibiotics providing levels of protection significantly greater than see with antibiotics or the antibody alone” (see, e.g., Nagy, Introduction). Moreover, Epshtein 2003 teaches that the medicament comprising HLA-DRB1 and β2-MG antibodies can be used to treat a immunopathological condition and diseases accompanied by a violation of the immune response (see, e.g., Epshtein 2003, English Translation, “Description”, pg. 2), which can encompass infections. Therefore, based on the teachings of Epshtein 2003, Nagy, and LiverTox, it would have been obvious to combine the HLA-DRB1 and β2-MG antibody medicament with an antibiotic, such as gentamicin, because the antibiotic and antibodies will synergistically interact to be more effective against bacterial infections. One would have expected success because Epshtein 2003, Nagy, and Domenech all teach compositions comprising antibodies and/or antibiotics.
Regarding claim 141 pertaining to the treatment of bacterial infections, these have been interpreted as intended use limitations and do not carry patentable weight. The intended use does not impart a structure limitation for the claimed product (i.e., the medicament) and the combined prior art of Epshtein 2003, Epshtein 2014, Nagy, and Domenech teaches the instantly composition; therefore, the structure is capable of performing the intended use.
Regarding the volume ratio limitations in claim 141, as discussed above, one of ordinary skill in the art would recognize these limitations are result effective variables which can be met as a matter of routine optimization. See MPEP 2144.05
Examiner’s Response to Arguments
Applicant's arguments filed 03/19/2026 have been fully considered but they are not persuasive.
Regarding Applicant’s arguments that Epstein 2003 pertains to graft rejection (remarks, pages 19-20), this argument is not persuasive because this is considered intended use for Epstein 2003. Epstein 2003 teaches “antibodies to the major histocompatibility complex antigen, HLA (predominantly Class I or II), or to the complex of the HLA molecule and its associated peptide” (see, e.g., Epshtein, 2003, English translation, “Description”, pg. 2) can include HLA-DRB1 and β2-MG. Epshtein 2003 teaches that the antibodies can be “a mixture of various, mainly hundreds, of homeopathic dilutions” (see, e.g., Epshtein 2003, English translation, pg. 1), which can include a 1:1 volume ratio, or other volume ratios, or other dilutions, of HLA-DRB1 and β2-MG antibodies. Epshtein 2003 teaches that the medicament is prepared “in the form of alcoholic or aqueous solutions” (see, e.g., Epshtein 2003, English translation, “Description”, pg. 2). These teachings from Epstein 2003 apply to the instantly claimed invention regardless of the intended use.
Regarding Applicant’s arguments pertaining to the prior art not teaching the treatment of bacterial and viral infections (remarks, page 20), as discussed above, these limitations are considered intended use limitations. The intended use does not impart a structure limitation for the claimed product (i.e., the medicament) and the combined prior art of Epshtein 2003, Epshtein 2014, Nagy, and/or Domenech teaches the instantly composition; therefore, the structure is capable of performing the intended use. Epstein 2003 and Epstein 2014 may show that the antibodies exhibit an immunotropic effect for graft-versus-host disease and viral disease; however, the claimed structure is capable of performing the intended use of treating bacterial infections. Therefore, the Epshtein 2003, Epshtein 2014, Nagy, and/or Domenech teaches the instantly composition, which is capable of performing the intended use of treating bacterial infections.
Regarding Applicant’s arguments pertaining to the teachings of Nagy and Domenech (remarks, page 21), as discussed above, these rejections have been withdrawn necessitated by Applicant’s amendments. Therefore, Applicant’s arguments are moot.
Conclusion
Claims 105-109, 111, 115, 130, 134-136, and 140-141 are rejected.
No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
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/NATALIE IANNUZO/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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